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OBJECTIVE: To evaluate the relevance of the Rheumatoid Arthritis Impact of Disease (RAID) score as a disease activity marker of rheumatoid arthritis (RA) in a teleconsultation setting. METHODS: A prospective, observational, 24-month, single-center study involving patients with RA who underwent teleconsultations was performed. The RAID score was sent to all patients by email and completed the day before the scheduled session. The RAID questionnaire was also completed just prior to the next scheduled face-to-face consultation. The same physician performed teleconsultation/in-person consultations and was unaware of the RAID results. RESULTS: We included 70 patients (mean age 50 [SD 14] yrs, mean disease duration 10 [SD 9] yrs). The RAID score correlated with the following items: patient global assessment (r 0.55, P < 0.001), patient-reported swollen joint count (r 0.50, P < 0.001), and Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) calculated with patient self-reported tender/swollen joints (r 0.74, P < 0.001). The RAID score completed during the next face-to-face consultation for 45 patients also correlated with the DAS28-CRP performed by the clinician (r 0.65, P < 0.001). A RAID score > 2 was associated with the best combination of sensitivity (94%) and specificity (43%) for the indication of rapid in-person consultation because of insufficiently controlled disease activity, with an area under the curve of 0.74. All 23 patients with RAID < 2 had no intercurrent flares; overall physician global assessment was 1.6 of 10 (SD 1.4), DAS28-CRP 1.5 (SD 0.2), and CRP 1.8 (SD 1.4) mg/L. CONCLUSION: Our findings reinforce the RAID score as a valuable tool in teleconsultation, exhibiting a good correlation with disease activity variables. Using a RAID score threshold of 2 during teleconsultations could distinguish patients with good disease control and those with the potential need for an in-person visit.
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Objective: Systemic sclerosis is an autoimmune disease characterized by fibrosis of the skin and internal organs including the lung. Mucosal-associated invariant T cells are innate-like T lymphocytes able to produce various cytokines and cytotoxic mediators such as granzyme B. A large body of evidence supports a role of mucosal-associated invariant T cells in autoimmune disease but more recent reports suggest also a potential role in fibrotic conditions. Therefore, we herein addressed the question as whether mucosal-associated invariant T cells may have an altered profile in systemic sclerosis. Methods: Mucosal-associated invariant T cell frequency was analyzed by flow cytometry, using fresh peripheral blood from 74 consecutive systemic sclerosis patients who were compared to 44 healthy donors. In addition, in-depth mucosal-associated invariant T cell phenotype and function were analyzed in unselected 29 women with systemic sclerosis who were compared to 23 healthy women donors. Results: Proportion of circulating mucosal-associated invariant T cells was significantly reduced by 68% in systemic sclerosis compared to healthy donors (0.78% in systemic sclerosis vs 2.5%, p < 0.0001). Within systemic sclerosis subsets, mucosal-associated invariant T cells were reduced in patients with interstitial lung disease (systemic sclerosis-interstitial lung disease) (0.56% vs 0.96% in patients without interstitial lung disease, p = 0.04). Moreover, in systemic sclerosis patients, mucosal-associated invariant T cells displayed an activated phenotype indicated by markedly increased CD69+ mucosal-associated invariant T cell frequency (20% mucosal-associated invariant T cell CD69+ compared to 9.4% in healthy donors, p = 0.0014). Interestingly, mucosal-associated invariant T cells from systemic sclerosis-interstitial lung disease patients had a more pronounced altered phenotype compared to systemic sclerosis without interstitial lung disease with a correlation between mucosal-associated invariant T cells expressing CCR6+ and mucosal-associated invariant T cell frequency (r = 0.8, p = 0.006). Conclusion: Circulating mucosal-associated invariant T cells were reduced and exhibited an activated phenotype in systemic sclerosis patients. This peripheral mucosal-associated invariant T cell deficiency may be related to enhanced apoptosis and/or homing in inflamed tissue, particularly in systemic sclerosis-interstitial lung disease patients.
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Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90â¯% effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300â¯mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21â¯% and 92â¯% after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.
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Anticorpos Monoclonais , COVID-19 , Mesocricetus , SARS-CoV-2 , Animais , SARS-CoV-2/imunologia , SARS-CoV-2/efeitos dos fármacos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/imunologia , COVID-19/imunologia , COVID-19/virologia , Humanos , Cricetinae , Tratamento Farmacológico da COVID-19 , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Modelos Animais de Doenças , Betacoronavirus/imunologia , Betacoronavirus/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Background: Fibromyalgia is a prevalent condition affecting 1-2% of the general population and can result in significant disability. Physicians and patients frequently encounter challenges in managing this condition. Aim: The aim of this study was to explore novel management approaches through a qualitative analysis of the doctor-patient relationship. Design and setting: Telephonic interviews were conducted with fibromyalgia patients to investigate their healthcare experiences. Methods: Qualitative analysis was performed on patients' narratives using interpretative phenomenological analysis, a methodology that delves into each individual's subjectivity. Results: A total of 19 adult patients with fibromyalgia, primarily middle-aged women (84% women, mean age 49.8 years), recruited from two university centers in Paris, were included in the study. The narratives of participants revealed substantial suffering and considerable functional impairment, which is paradoxical for a condition often considered benign. They reported an ongoing sense of loss of control, exacerbated by an imbalanced patient-doctor relationship. Patients constantly feared not being heard or believed, and they frequently sought attention from their caregivers. Most participants displayed significant ambivalence toward the nature of their condition and actively sought causal links. Patients' adaptive strategies sometimes worsened their symptoms, as in the case of muscular deconditioning. The healthcare system appeared deficient in managing these patients, characterized by a lack of health professional training, frequent inappropriate responses from healthcare providers, and stigmatization of psychological conditions. Conclusion: Despite its perceived benign nature, fibromyalgia should be regarded as a severe condition due to its substantial long-term consequences. Participants reported a challenging experience with the doctor-patient relationship, marked by a strong sense of dependence and a lack of recognition. The care pathway for these patients appeared unsuitable and disorderly, potentially resulting in iatrogenic consequences. The management of patients with fibromyalgia should be enhanced and directed toward a patient-centered approach. The study provides practical recommendations regarding communication methods and patient care.
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BACKGROUND: Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years. METHODS: The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR-EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR-EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done. RESULTS: Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7-5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7-10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17). INTERPRETATION: Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials. FUNDING: European Scleroderma Trial And Research and World Scleroderma Foundation.