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BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. PATIENTS AND METHODS: We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3. RESULTS: Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268-4501) occurring at 13 weeks (IQR 4-36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. CONCLUSION: These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.
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Asma , Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Humanos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/diagnóstico , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/tratamento farmacológico , Estudos Retrospectivos , Prednisona/uso terapêutico , Resultado do Tratamento , Asma/tratamento farmacológico , Asma/complicações , Eosinofilia/tratamento farmacológico , Eosinofilia/complicações , RecidivaRESUMO
OBJECTIVES: The aim of the present study was to evaluate performance of serum and synovial fluid levels of the granulocyte protein calprotectin as inflammatory biomarker in rheumatoid arthritis (RA) patients with knee synovitis. METHODS: 76 RA patients with ongoing knee synovitis were included. Data on disease activity score with 28 joints and their subcomponents and radiological destruction of the affected knee were collected. White blood cell count, C-reactive protein, anti-citrullinated peptide antibodies (ACPA) against cyclic citrullinated peptide version 2 (anti-CCP2), IgM rheumatoid factor (RF) and calprotectin were analysed in parallel in circulation and in synovial fluid (SF). Counts of polynuclear and mononuclear cells were measured in SF. RESULTS: Serum (S) calprotectin correlated stronger than SF-calprotectin with inflammatory markers and disease activity. Instead, SF-calprotectin showed a strong correlation to SF counts of white blood cells, and especially to polymorphonuclear cell counts (Spearman's rho = 0.72, p< 0.001). S-calprotectin showed markedly stronger correlation with inflammatory markers and disease activity in ACPA positive as compared with ACPA negative RA patients; a similar difference was observed for patients with and without IgM RF. CONCLUSION: The particularly strong association between circulating calprotectin and inflammation in ACPA positive RA is a new argument for a specific role for polymorphonuclear granulocytes/neutrophils in this RA subset. Measurement of calprotectin in SF does not convey any additional benefit compared with measurement in the circulation in RA patients with knee synovitis.
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OBJECTIVE: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. METHODS: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. RESULTS: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. CONCLUSIONS: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Feminino , Humanos , Masculino , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Mieloblastina/genética , Mieloblastina/imunologia , Peroxidase/genética , Peroxidase/imunologia , Caracteres SexuaisRESUMO
OBJECTIVE: To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). METHODS: Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. RESULTS: PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10-61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10-44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10-10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10-25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10-7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. CONCLUSION: We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Anticorpos Anticitoplasma de Neutrófilos , Células Endoteliais , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/genética , Humanos , Poliangiite Microscópica/complicações , Poliangiite Microscópica/genética , Mieloblastina/genética , PeroxidaseRESUMO
INTRODUCTION: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis. METHODS: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation. RESULTS: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation. CONCLUSIONS: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.
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Anticorpos Antiproteína Citrulinada/análise , Complexo Antígeno-Anticorpo/análise , Artrite Reumatoide/imunologia , Líquido Sinovial/imunologia , Adulto , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Especificidade de Anticorpos , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF. METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3. RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients. CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.
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Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Autoanticorpos/sangue , Catepsina L/análise , Catepsina L/sangue , Catepsinas/análise , Catepsinas/sangue , Líquido Sinovial/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Masculino , Metaloproteinase 3 da Matriz/sangue , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Fenótipo , Fator Reumatoide/sangue , Índice de Gravidade de DoençaAssuntos
Complemento C1q/deficiência , Doenças da Deficiência Hereditária de Complemento/sangue , Interferon-alfa/sangue , Lúpus Eritematoso Sistêmico/sangue , Feminino , Doenças da Deficiência Hereditária de Complemento/complicações , Humanos , Lúpus Eritematoso Sistêmico/complicações , Adulto JovemAssuntos
Granulomatose com Poliangiite/complicações , Linfoma/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/mortalidade , Humanos , Imunossupressores/uso terapêutico , Linfoma/diagnóstico , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Access to healthy foods, especially for those who are living with diabetes and hypertension, is crucial in managing these chronic diseases. This study evaluates the implementation of a food pharmacy and food prescription program at a safety-net hospital that serves vulnerable populations. Patients who screen as food insecure using the USDA adult food security survey receive a referral from the physician to the food pharmacy program where a dietician reviews their dietary requirements based on their chronic disease and develops a diet plan. Patients then receive fresh produce, meats and other products every 2 weeks that meets their nutritional needs from the food pharmacy. Biometric data from the patient's most recent clinic visit at the time of enrollment was collected as the baseline measures including blood pressure, weight, and HbA1c (if diabetic). Additionally, biometric information was collected from the patient's medical records from regularly scheduled clinic visits at 6 month intervals. A total of 266 patients were enrolled in the program during the 13-month period that was studied (121 patients with 6-month data and 68 patients with 12-month data). The statistical analysis showed a significant improvement in diastolic blood pressure at 12 months and in weight at both the 6 months and 12 months timeframes when comparing to baseline biometrics.
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ABSTRACT: Given its role as a safety net institution, the University of Florida Health (UF Health) Jacksonville has responded to the community's needs through partnerships with the community for decades. Such academic-community partnerships have a broad emphasis on population health and primary care that expands the model of care to include community engagement, which allows such partnerships to promote health and well-being and reduce health inequalities by addressing social determinants of health (SDOH).This report describes the UF Health Jacksonville and University of Florida College of Medicine - Jacksonville's creation of the Urban Health Alliance (UHA) in June 2019 due to continued poor health outcomes and inequities within the community. The mission of the UHA is to improve community health using community-focused, self-sustainable strategies and solutions to impact SDOH (i.e., more upstream interventions). Using the tenets of the collective impact model, the UHA acts as a backbone organization to achieve these objectives by empowering community partners to affect changes in policy, systems, and other structures necessary for the optimal health of the community. The UHA's work is divided across 4 pillars: services, research, education, and policy. These pillars reflect the traditional missions of academic medical centers-clinical care, research, and education-and the need to address structural changes to improve community health-namely, policy. By addressing the issues that most impact the patients and community of UF Health Jacksonville, the UHA can serve as an example of how an academic medical center can use the traditional missions to improve the community's health and move toward health equity.
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OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV. METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively. RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Anticorpos Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Mieloblastina/genética , Genótipo , RecidivaRESUMO
OBJECTIVES: To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking. METHODS: Through Swedish registers, we identified 13 493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age. RESULTS: Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%). CONCLUSIONS: As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
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Doenças Cardiovasculares , Inibidores de Janus Quinases , Humanos , Idoso , Suécia/epidemiologia , Fumantes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Fator de Necrose Tumoral alfa , Inibidores do Fator de Necrose Tumoral , Fatores de Risco de Doenças CardíacasAssuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Encéfalo/diagnóstico por imagem , Encefalite Transmitida por Carrapatos/complicações , Lúpus Eritematoso Sistêmico/complicações , Rituximab/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Encefalite Transmitida por Carrapatos/diagnóstico por imagem , Evolução Fatal , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imageamento por Ressonância MagnéticaRESUMO
Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Toxidermias/etiologia , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Artrite Reumatoide/patologia , Relação Dose-Resposta a Droga , Toxidermias/tratamento farmacológico , Toxidermias/prevenção & controle , Humanos , Injeções Subcutâneas/efeitos adversos , Injeções Subcutâneas/métodos , Injeções Subcutâneas/normasRESUMO
OBJECTIVE: To investigate the possible association between animal exposure and risk for granulomatosis with polyangiitis (GPA). METHODS: Patients with GPA at the Department of Rheumatology, Uppsala University Hospital, between January 1, 2011, and December 31, 2018, were consecutively included. All patients filled in a questionnaire on possible environmental exposures: occupation, hobbies, and animal contact. As controls we included 128 patients with rheumatoid arthritis (RA) and 248 population controls collected from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, matched for age, sex, and geographical area of residence. The controls filled out a questionnaire on current and past contact with farming and animals, at the time of the RA patient's diagnosis. RESULTS: A total of 62 patients with GPA, 128 patients with RA, and 248 population controls were included in the study. GPA was significantly associated with horse exposure, with a 2- to 3-fold increased risk compared with RA (OR 3.08, 95% CI 1.34-7.08) and population controls (OR 2.61, 95% CI 1.29-5.29). Borderline increased risks were found for any animal contact, but no association was found when analyzing contact with cats/dogs only. A significant association was found between GPA and farming compared to the population controls (OR 7.60, 95% CI 3.21-17.93). CONCLUSION: This study has identified for the first time, to our knowledge, a significant association between exposure to specific animals, namely horses, and the development of GPA. The results also support previous studies reporting an association between farming and GPA, underscoring the possibility of exogenous factors as initiators in the development of GPA.
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Artrite Reumatoide , Granulomatose com Poliangiite , Agricultura , Animais , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Estudos de Casos e Controles , Gatos , Cães , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/etiologia , Cavalos , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.
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BACKGROUND: Wegener's granulomatosis is a systemic vasculitis of unknown aetiology. Previous studies have presented environmental exposures such as silica and farming as potential risk factors. OBJECTIVE: To investigate the potential risk for Wegener's granulomatosis associated with occupations involving contact with animals and various airway exposures, using a population-based approach. METHODS: In the Swedish Register of inpatient care 2288 cases with Wegener's granulomatosis were identified. Ten matched controls for every case were selected from the Swedish Population Register. By linking the cases and controls to the Swedish population censuses, information on employments before the diagnosis of Wegener's granulomatosis was collected. Relative risks were assessed as odds ratios using conditional logistic regression. RESULTS: Odds ratios for specific occupations ranged from 0.6 to 1.9, and centred symmetrically around 1. No statistically significant increased risk was noted for the investigated occupations.
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Granulomatose com Poliangiite/etiologia , Doenças Profissionais/etiologia , Métodos Epidemiológicos , Feminino , Granulomatose com Poliangiite/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Ocupações/estatística & dados numéricos , Suécia/epidemiologiaRESUMO
BACKGROUND/OBJECTIVE: Impaired ability to perform skilled movements with the left upper limb in patients with corpus callosum injury has been well described (callosal apraxia) with some displaying spatial-temporal errors primarily in response to verbal commands (verbal callosal disconnection apraxia), with imitation, and when using actual tools (callosal ideomotor apraxia). Additionally some patients with callosal injury also make content errors when selecting and using the incorrect tool with their left upper limb (callosal conceptual apraxia). Interestingly, patients with Alzheimer's disease (AD) reveal anatomic evidence of callosal degeneration but callosal apraxia in AD has not been described. The purpose of this study was to learn whether patients with AD display forms of callosal apraxia. METHOD: Participants were 22 right-handed patients with AD and 24 matched controls. Both upper limbs were tested by having subjects pantomime transitive movements to command and imitation. Participants also viewed pictures of an incomplete task and attempted to pantomime the action needed to complete the task. RESULTS AND CONCLUSIONS: When compared to controls, the participants with AD demonstrated ideomotor and conceptual apraxias of both upper limbs; however, ideomotor apraxia of their left hand was more robust than that of their right hand, suggesting a hemispheric disconnection.
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Doença de Alzheimer/complicações , Apraxia Ideomotora/complicações , Corpo Caloso/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Apraxia Ideomotora/fisiopatologia , Feminino , Mãos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologiaRESUMO
BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX). METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥ 60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test. RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05). CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.
Assuntos
Artrite Reumatoide/imunologia , Encefalite Transmitida por Carrapatos/prevenção & controle , Hospedeiro Imunocomprometido , Vacinas Virais/uso terapêutico , Adulto , Idoso , Anticorpos Antivirais/sangue , Formação de Anticorpos , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Imunização Secundária , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vacinas Virais/imunologiaRESUMO
OBJECTIVE: Failure to rapidly identify high-value information due to inappropriate output may alter user acceptance and satisfaction. The information needs for different intensive care unit (ICU) providers are not the same. This can obstruct successful implementation of electronic medical record (EMR) systems. We evaluated the implementation experience and satisfaction of providers using a novel EMR interface-based on the information needs of ICU providers-in the context of an existing EMR system. METHODS: This before-after study was performed in the ICU setting at two tertiary care hospitals from October 2013 through November 2014. Surveys were delivered to ICU providers before and after implementation of the novel EMR interface. Overall satisfaction and acceptance was reported for both interfaces. RESULTS: A total of 246 before (existing EMR) and 115 after (existing EMR+novel EMR interface) surveys were analyzed. 14% of respondents were prescribers and 86% were non-prescribers. Non-prescribers were more satisfied with the existing EMR, whereas prescribers were more satisfied with the novel EMR interface. Both groups reported easier data gathering, routine tasks & rounding, and fostering of team work with the novel EMR interface. This interface was the primary tool for 18% of respondents after implementation and 73% of respondents intended to use it further. Non-prescribers reported an intention to use this novel interface as their primary tool for information gathering. CONCLUSION: Compliance and acceptance of new system is not related to previous duration of work in ICU, but ameliorates with the length of EMR interface usage. Task-specific and role-specific considerations are necessary for design and successful implementation of a EMR interface. The difference in user workflows causes disparity of the way of EMR data usage.