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1.
Medicine (Baltimore) ; 99(35): e21827, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871905

RESUMO

To retrospectively evaluate initial tumor necrosis factor inhibitor (TNFi) failure patients for clinical predictors of response to a 2nd TNFi in our 4282 rheumatoid arthritis (RA) patient database.A cross-sectional retrospective manual chart review of the electronic health record (EHR) was performed on 322 "real world" RA patients who were prescribed 2 TNFis. Response to TNFi was determined by the treating provider who had real time Clinical Disease Activity Index (CDAI) scores to inform treatment decisions. Age, gender, body mass index (BMI), insurance provider, duration of disease, cyclic citrullinated peptide antibody (CCP) and rheumatoid factor (RF) positivity, concomitant disease modifying anti-rheumatic drug therapy, length of time between diagnosis and start of 1st and 2nd TNFi, transient efficacy of 1st TNFi (defined as response to TNFi at 3 months but later lost response), and reason for discontinuation of 1st TNFi were analyzed. A multivariable logistic regression model was used to model response to a 2nd TNFi.Response proportions to the 2nd TNFi were greater in females (161/223, 72.2% response female vs 41/75, 54.7% male, P < .01), those who began their 1st TNFi within 3 months of their RA diagnosis, and in RF+ patients (123/170, 72.4% response seropositive vs 66/110, 60.0% seronegative, P < .03). The higher female response rate was independent of age, BMI, and seropositivity.In RA patients who failed an initial TNFi, female patients and patients with RF+ were more likely to have a clinical response to a 2nd TNFi. In the absence of these predictors, stronger consideration for choosing a biologic with an alternative mechanism of action might be given when the 1st TNFi fails.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/sangue , Fatores Sexuais , Tempo para o Tratamento
2.
RMD Open ; 6(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32878994

RESUMO

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. METHODS: Using an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. RESULTS: Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. CONCLUSIONS: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Sistema de Registros , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Alemanha , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Hospitalização , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Polimialgia Reumática/complicações , Polimialgia Reumática/tratamento farmacológico , Prognóstico , Doenças Reumáticas/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Adulto Jovem
3.
Rheumatol Int ; 40(11): 1741-1751, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32880032

RESUMO

Repurposing of antirheumatic drugs has garnered global attention. The aim of this article is to overview available evidence on the use of widely used antirheumatic drugs hydroxychloroquine, methotrexate and colchicine for additional indications. Hydroxychloroquine has endothelial stabilizing and anti-thrombotic effects. Its use has been explored as an adjunctive therapy in refractory thrombosis in antiphospholipid syndrome. It may also prevent recurrent pregnancy losses in the absence of antiphospholipid antibodies. Hydroxychloroquine favourably modulates atherogenic lipid and glycaemic profiles. Methotrexate has been tried for modulation of cardiovascular events in non-rheumatic clinical conditions, although a large clinical trial failed to demonstrate a benefit. Colchicine has been shown to successfully reduce the risk of recurrent cardiovascular events in a large multicentric trial. Potential antifibrotic effects of colchicine require further exploration. Hydroxychloroquine, methotrexate and colchicine are also being tried at different stages of the ongoing Coronavirus Disease 19 (COVID-19) pandemic for prophylaxis and treatment. While the use of these agents is being diversified, their adverse effects should be timely diagnosed and prevented. Hydroxychloroquine can cause retinopathy and rarely cardiac and auditory toxicity, retinopathy being dose and time dependent. Methotrexate can cause transaminitis, cytopenias and renal failure, particularly in acute overdoses. Colchicine can rarely cause myopathies, cardiomyopathy, cytopenias and transaminitis. Strong evidence is warranted to keep balance between benefits of repurposing these old antirheumatic drugs and risk of their adverse effects.


Assuntos
Antirreumáticos/uso terapêutico , Betacoronavirus , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Colchicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Metotrexato/efeitos adversos , Pandemias
4.
PLoS Med ; 17(9): e1003296, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32960885

RESUMO

BACKGROUND: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. METHODS AND FINDINGS: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included. CONCLUSIONS: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Adulto , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Autoanticorpos/genética , Autoanticorpos/imunologia , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Índice de Gravidade de Doença
5.
Front Immunol ; 11: 2094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973818

RESUMO

The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1ß, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.


Assuntos
Betacoronavirus , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Terapia de Alvo Molecular/métodos , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Butirofenonas/farmacologia , Butirofenonas/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Coronavirus/virologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pneumonia Viral/virologia , Purinas/farmacologia , Purinas/uso terapêutico , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico
6.
Georgian Med News ; (304-305): 95-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965257

RESUMO

The aim of the research was to determine liver lesion in patients with Oligoarticular and RF-negative Polyarticular forms of JIA by noninvasive methods depending on duration of Methotrexate treatment. The study included 42 patients with Rheumatoid factor (RF) negative oligo- and polyarticular joints forms of JIA from 3 to 18 years old. They were investigated by measurement of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), haptoglobin, triglycerides, gamma glutamine transferase (GGT), apolipoprotein-A (Apo-A), a2-macroglobulin, cholesterine levels. The equation for calculating the FibroTest score regression coefficient had been done according U.S. patent 6.631.330. Student -Fisher Test, Mann - Whitney U-test were used for the statistical processing. In spite of MTX treatment progression of JIA was determined according assessment of joints functional class and radiological stage (p<0.05). Increased level of ALAT was prominent (40%) in children taken MTX for 1-5 years in comparison with other studied patients (p<0.05). 17 % of children who took MTX longer than 5 years had increased GGT content. Metabolic liver function was not changed because levels of Apo-A, haptoglobin, total bilirubin, cholesterine were within normal limits due to all stages of MTX taking. The increased level of a2-macroglobulin as a predictor of liver fibrosis was determined in all studying groups with the average frequency 36 % and it did not correspond to the duration of MTX treatment. According FibroTest score regression 14% of patients had liver fibrosis F1, which did not depend on duration of MTX treatment. According to our findings, patients using MTX for JIA management had joint damage progresses despite usage of MTX. Hepatic cytolysis is most frequently appeared within 15 years of MTX taking. Risk of liver fibrosis does not depend on duration of MTX treatment.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Neoplasias Hepáticas , Adolescente , Alanina Transaminase , Criança , Pré-Escolar , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento
7.
Clin Rheumatol ; 39(11): 3237-3244, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892311

RESUMO

The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled with immunosuppressive agents they take which predisposes them to a host of infections. Data on COVID-19 patients with underlying rheumatological diseases has been emerging mostly in the form of small case series and one global registry. From these data, it seems like our patients, although immunosuppressed, are not particularly susceptible to the coronavirus infection and if infected, do not have significantly worse outcomes than other patients. In fact, drugs like hydroxychloroquine, dexamethasone, and tocilizumab have been studied for treatment of COVID-19. However, this is only preliminary data, and since a few parts of the world are still grappling with the pandemic at its peak, we need to be equipped on how to protect and manage our immunosuppressed patients. Published evidence to guide treatment decisions are lacking and doubts regarding continuation and initiation of immunosuppressants remain. Rheumatoid arthritis (RA) is the most common immune-mediated disorder in COVID-19 patients, and in this review, we discuss how the commonly used drugs in RA alter the patients' susceptibility to this infection. The review also summarizes the recommendations from the major bodies on how to manage this disease in these times. Key Points • Patients on immunosuppressive medications are not found to be at a greatly increased risk of acquiring COVID-19 infection. • Patients doing well on a stable dose of steroid and/or Disease-Modifying Antirheumatic Drugs (DMARDs) should be allowed to continue the same unless they get infected in which case, temporary stoppage of methotrexate and leflunomide may be considered. • Initiation of high-dose steroids, DMARDs, and biologics, if the clinical situation demands so, can be done. • Maintenance biologic therapy for stable patients should be individualized by the treating physician.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus , Glucocorticoides/uso terapêutico , Pandemias , Pneumonia Viral , Anti-Inflamatórios não Esteroides/uso terapêutico , Betacoronavirus , Produtos Biológicos/uso terapêutico , Desprescrições , Gerenciamento Clínico , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico
8.
Clin Rheumatol ; 39(11): 3245-3254, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895747

RESUMO

Rheumatology practice, during Coronavirus Disease 2019 (COVID-19) pandemic, has faced multifaceted challenges. Rheumatologists routinely prescribe immunosuppressant medications to their patients with multisystem autoimmune rheumatic diseases who are concerned about the increased risk of acquiring COVID-19 infection and are anxious to know if they should continue or hold these medications. Rheumatologists are often inundated by calls from their patients and physician colleagues caring for COVID-19 patients in hospitals, about how to manage the immunosuppression. Physicians face the challenging task of keeping up with the most up-to-date information on COVID-19. There are uncertainties about the mode of spread, clinical features, management options as well as long-term complications of COVID-19. Data are rapidly evolving and different studies on treatment options are showing contradictory results. It is known that viral illnesses can trigger a flare-up of underlying rheumatic disease that was previously in remission. To further complicate the scenario, some of the immunosuppressants have shown to have antiviral properties. This has created dilemma in the light of current COVID-19 crisis, as whether to continue or stop the immunosuppressive agents which could be essential to prevent complications of the rheumatic diseases including organ failure but also there is concern about acquiring COVID-19 or developing serious infection. Until we get an effective vaccine, immunosuppressant management for rheumatic diseases as well as other autoimmune diseases and transplants will pose difficult questions. This article is an attempt to review and understand COVID-19 and its impact on the immune system with special emphasis on managing medications used for autoimmune rheumatic diseases. We have provided general guidance about decision making, in regards to the immunosuppressive agents used in rheumatology practice with an understanding that this may change in near future.


Assuntos
Antirreumáticos/uso terapêutico , Infecções por Coronavirus/imunologia , Imunossupressores/uso terapêutico , Pneumonia Viral/imunologia , Doenças Reumáticas/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Desprescrições , Gerenciamento Clínico , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico
9.
Rheumatol Int ; 40(10): 1593-1598, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32794113

RESUMO

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Glucocorticoides/uso terapêutico , Hospitalização/estatística & dados numéricos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Idoso , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Artrite Psoriásica/complicações , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Azitromicina/uso terapêutico , Betacoronavirus , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Modelos Logísticos , Lopinavir/uso terapêutico , Pneumopatias/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Estudos Retrospectivos , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais , Espanha/epidemiologia
10.
Z Rheumatol ; 79(7): 710-717, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32809050

RESUMO

BACKGROUND: Reliable data on the course and treatment of pediatric COVID-19 ("corona virus disease 2019") in immunosuppressed patients with rheumatic diseases are missing. AIM: Delineation of individual strategies of the members of the Society for Pediatric Rheumatology (GKJR) in cases of COVID-19. METHODS: In May 2020 all GKJR members were invited to take part in an online survey. Opinion data regarding an approach using disease-modifying anti-rheumatic drugs (DMARD) in cases of COVID-19 as well as the readiness to use new therapeutic agents in patients in different stages of the disease were collected. RESULTS: A total of 71 respondents (27.3% of all contacted pediatric rheumatologists) took part in the survey. Of these 28.2% had treated patients with COVID-19. Over 95% of the respondents did not support a preventive adaptation of the anti-rheumatic treatment during the SARS-CoV­2 pandemic. In the case of outpatients under immunosuppression with proven COVID-19 more than 50% of the respondents would refrain from administering intravenous high-dose steroids, cyclophosphamide, anti-CD20 antibodies as well as BAFF, CTLA­4 and TNF-alpha blockades. Conversely, >70% of the respondents would continue the treatment with nonsteroidal anti-inflammatory drugs, hydroxychloroquine (HCQ), oral steroids, mycophenolate, IL­1 blockade and immunoglobulins (Ig). In the case of inpatients 74.6% of respondents would consider targeted COVID-19 treatment. In stable patients with oxygen treatment (stage I) HCQ (18.3%), azithromycin (16.9%) and Ig (9.9%) were most frequently used. In cases of early signs (stage II) or a manifest cytokine storm (stage III) anakinra (40.8% for stage II and 46.5% for stage III), tocilizumab (26.8% and 40.8%, respectively), steroids (25.4% and 33.8%, respectively) and remdesivir (29.6% and 38.0%, respectively) were most frequently used. The need for a personalized approach based on the current clinical situation was emphasized by many respondents. CONCLUSION: The currently low prevalence of COVID-19 in Germany limits the general clinical experience. Therefore, the presented results have to be interpreted with caution and mostly as hypothetical treatment considerations. It is to be expected that there will always be a limited amount of evidence on pediatric COVID-19; therefore, a continuous and critical exchange of expert opinions on the treatment strategies is important.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Reumatologistas , Antirreumáticos/uso terapêutico , Betacoronavirus , Criança , Infecções por Coronavirus/tratamento farmacológico , Alemanha , Humanos , Pandemias , Inquéritos e Questionários
11.
Z Rheumatol ; 79(7): 686-691, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32845393

RESUMO

The recommendations of the German Society of Rheumatology (DGRh) update, which update and expand the guidance on the management of patients with inflammatory rheumatic diseases in view of SARS-CoV­2 created at the beginning of the COVID-19 pandemic, correspond in many points with the recommendations for action of the American (ACR) and European (EULAR) societies, but also differ in some points. Therefore, this article discusses the core recommendations of the DGRh update on the prevention of SARS-CoV-2/COVID-19, the risk assessment for inflammatory rheumatic diseases and the use of antirheumatic treatments in the context and in comparison to the ACR and EULAR recommendations, and provides an overview of the risk assessment of individual antirheumatic drugs.


Assuntos
Antirreumáticos/uso terapêutico , Infecções por Coronavirus/epidemiologia , Inflamação/terapia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/terapia , Reumatologia , Betacoronavirus , Europa (Continente) , Alemanha , Humanos , Pandemias , Guias de Prática Clínica como Assunto , Medição de Risco , Sociedades Médicas , Estados Unidos
12.
Cells ; 9(8)2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796683

RESUMO

The development of biological disease-modifying antirheumatic drugs (bDMARDs) and target synthetic DMARDs (tsDMARDs), also known as small molecule inhibitors, represent a breakthrough in rheumatoid arthritis (RA) treatment. The tsDMARDs are a large family of small molecules targeting mostly the several types of kinases, which are essential in downstream signaling of pro-inflammatory molecules. This review highlights current challenges associated with the treatment of RA using small molecule inhibitors targeting intracellular JAKs/MAPKs/NF-κB/SYK-BTK signaling pathways. Indeed, we have provided the latest update on development of small molecule inhibitors, their clinical efficacy and safety as a strategy for RA treatment. On the other hand, we have highlighted the risk and adverse effects of tsDMARDs administration including, among others, infections and thromboembolism. Therefore, performance of blood tests or viral infection screening should be recommended before the tsDMARDs administration. Interestingly, recent events of SARS-CoV-2 outbreak have demonstrated the potential use of small molecule inhibitors not only in RA treatment, but also in fighting COVID-19 via blocking the viral entry, preventing of hyperimmune activation and reducing cytokine storm. Thus, small molecule inhibitors, targeting wide range of pro-inflammatory singling pathways, may find wider implications not only for the management of RA but also in the controlling of COVID-19.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Citocinas/metabolismo , Quimioterapia Combinada , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Camundongos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacos
13.
BMJ Open Respir Res ; 7(1)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32847947

RESUMO

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Associada a Assistência à Saúde/epidemiologia , Hipóxia/terapia , Intubação Intratraqueal/estatística & dados numéricos , Oxigenoterapia/métodos , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Corticosteroides/uso terapêutico , Afro-Americanos , Idoso , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Cânula , Comorbidade , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Cardiopatias/epidemiologia , Hispano-Americanos , Humanos , Hidroxicloroquina/uso terapêutico , Hipertensão/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Philadelphia/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Viral/epidemiologia , Pulsoterapia , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fumar/epidemiologia
15.
Ann Rheum Dis ; 79(11): 1393-1399, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32769150

RESUMO

OBJECTIVES: To describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19. METHODS: An observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission. RESULTS: The study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model. CONCLUSION: Our results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/terapia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/terapia , Doenças Reumáticas/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Betacoronavirus , Diabetes Mellitus/epidemiologia , Feminino , Glucocorticoides/uso terapêutico , Cardiopatias/epidemiologia , Humanos , Hipertensão/epidemiologia , Tempo de Internação/estatística & dados numéricos , Estudos Longitudinais , Pneumopatias/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Doença Mista do Tecido Conjuntivo/epidemiologia , Análise Multivariada , Pandemias , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/epidemiologia , Fatores de Proteção , Doenças Reumáticas/tratamento farmacológico , Fatores de Risco , Fatores Sexuais , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/epidemiologia , Espanha/epidemiologia , Espondiloartropatias/tratamento farmacológico , Espondiloartropatias/epidemiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico
16.
PLoS One ; 15(8): e0237143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760165

RESUMO

OBJECTIVES: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. METHODS: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. RESULTS: In methotrexate/Abatacept responders, 672 genes were significantly (q<0.05) dysregulated at 6 months compared to baseline. Correlation analysis highlighted 19 genes whose dysregulations were significantly associated with disease activity variation (p<0.05) and whose functions were associated with proliferation, apoptosis of cells and mitochondrial metabolism, suggesting a restoration of oxidative signaling. The other 653 gene expression changes were relative to direct or indirect effects of methotrexate/Abatacept treatment and were significantly (p<0.005) involved in pathways relative to mRNA processing, proteasome, angiogenesis, apoptosis and TCR signaling. This study highlights new mechanisms of action of methotrexate/Abatacept and may provide new therapeutic targets to prevent autoimmunity in rheumatoid arthritis.


Assuntos
Abatacepte/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacologia , Transcriptoma/efeitos dos fármacos , Abatacepte/administração & dosagem , Abatacepte/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade
17.
Arthritis Care Res (Hoboken) ; 72(9): 1248-1256, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32754989

RESUMO

OBJECTIVE: To examine the risk of incident type 2 diabetes mellitus (DM) among patients with rheumatoid arthritis (RA) versus the risk among 4 different comparison cohorts. METHODS: Using a large US commercial insurance database, Optum Clinformatics Data Mart (2005-2017), we identified patients with RA based on ≥2 diagnoses for RA and use of ≥1 disease-modifying antirheumatic drug. We selected 4 comparison cohorts with ≥2 disease-specific diagnoses and ≥1 dispensing of disease-specific drugs: 1) general non-RA patients, 2) patients with hypertension, 3) patients with osteoarthritis (OA), and 4) patients with psoriatic arthritis (PsA). The index date was the disease-specific drug dispensing date. Patients with RA were matched to the comparator cohorts (except PsA) for age as of the index date, sex, and index date. The primary outcome was incident type 2 DM, defined as a new diagnosis of type 2 DM plus a new dispensing of antidiabetic drugs. A multivariable Cox proportional hazards model estimated hazard ratios of incident type 2 DM among RA versus each of the comparison cohorts, accounting for >40 baseline covariates. RESULTS: A total of 449,327 RA, general non-RA, hypertension, OA, or PsA patients were selected. During the median of 1.6 (range 0.6-3.3) years of follow-up, the incidence rate of type 2 DM was the lowest in the RA cohort (7.0 per 1,000 person-years) and highest (12.3 per 1,000 person-years) in the hypertension cohort. After adjusting for >40 baseline covariates, we found that RA was associated with a 24-35% lower risk of incident type 2 DM compared to 4 comparison groups. CONCLUSION: In this large population-based cohort study, patients with RA had a lower rate of incident type 2 DM compared to the general non-RA, hypertension, OA, and PsA cohorts.


Assuntos
Artrite Reumatoide/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Estudos Retrospectivos , Risco
18.
Scand J Rheumatol ; 49(4): 267-270, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32757727

RESUMO

OBJECTIVES: Substantial changes in the handling of patients with inflammatory arthritis have occurred during the past half century. Polyarticular psoriatic arthritis (PsA) has been treated with the same synthetic disease-modifying anti-rheumatic drugs (DMARDs) as rheumatoid arthritis (RA), but for PsA there is less documentation regarding their effect. For biologic DMARDs, evidence of effect is more convincing. We have previously investigated the risk of orthopaedic surgery in patients with RA and PsA to see whether the change in treatment over time has improved the long-term outcome of inflammatory arthritis. For RA, patients diagnosed from 1999 onwards had a lower risk of surgery than patients diagnosed in earlier years. For PsA, the risk of surgery did not change similarly. We wished to compare RA patients to PsA patients with regard to medical and surgical treatment. METHOD: We compared a historic cohort of 1010 RA patients diagnosed in 1972-2009 to a historic cohort of 590 PsA patients diagnosed in 1954-2011. RESULTS: PsA patients received significantly less medical treatment both in the first year of disease and during the disease course. Risk of surgery during the disease course was lower for PsA than for RA (20% vs 31%). The risk of surgery in RA patients diagnosed from 1999 onwards was similar to that of PsA patients. CONCLUSIONS: PsA patients received less intensive treatment than RA patients. Their prognosis, regarding orthopaedic surgery, was also less severe. Contrary to RA, the change in treatment did not have beneficial effects regarding the risk of orthopaedic surgery.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/cirurgia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/cirurgia , Procedimentos Ortopédicos/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Clin Rheumatol ; 39(11): 3195-3204, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32852623

RESUMO

INTRODUCTION: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic. METHOD: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test. RESULTS: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011). CONCLUSIONS: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/epidemiologia , Dermatomiosite/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/fisiopatologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/fisiopatologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Doenças do Tecido Conjuntivo Indiferenciado/tratamento farmacológico , Doenças do Tecido Conjuntivo Indiferenciado/epidemiologia , Doenças do Tecido Conjuntivo Indiferenciado/fisiopatologia
20.
Brasília; s.n; 4 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117744

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 13 protocolos.


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Tetraciclinas/uso terapêutico , Vitamina D/uso terapêutico , Cloroquina/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Antirreumáticos/uso terapêutico , Ritonavir/uso terapêutico , Etoposídeo/uso terapêutico , Lopinavir/uso terapêutico , Hidroxicloroquina/uso terapêutico
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