Ease in Emergency Hospital Visits Due to Covid-19 Following Implementation of a Telemedicine Service in Ceará, Brazil.

Background: We assessed the impact of implementing a virtual emergency room (VER) in easing emergency room (ER) visits in patients suspected of having COVID-19. Materials and Methods: Retrospective observational cohort study conducted in May 2020 and in March 2021, during the first and second waves in Brazil. Patients could choose to either visiting ER or using the VER (implemented in March 2021). Medical records were revised for demographic and clinical data. The primary outcome was the number of visits. Results: A total of 32,822 visits were evaluated. HR was more than three times less in the VER group with <10% VER clients going to ER. The trend and volume of use of the emergency sector in the periods did not show a statistically significant difference, despite the higher number of cases in the second period. Conclusion: This telemedicine strategy led to a reduction in visits to the ER. Also, our results suggest the safety of this intervention.

Prevalence of Inflammatory Back Pain in a Low-Income Population.

BACKGROUND: Inflammatory back pain (IBP) is a major criterion in identifying axial spondyloarthritis. Whether socioeconomic issues impact prevalence of IBP assessed using standardized questionnaires has not been assessed. We determined IBP prevalence and performance of IBP questionnaires in a low-income, low-literacy population. METHODS: Individuals were interviewed in Fortaleza, Brazil, for the prevalence of IBP using Calin's, Berlin, and ASAS IBP questionnaires; monthly family income (US dollars), literacy (>/≤8 school years [SYs]), and smoking habit (present/absent) were registered. RESULTS: Two hundred nineteen individuals were included (mean age, 38.2 ± 12.9 years), 110 (50.2%) men, 58 (26.4%) White, and 38 (17.3%) smokers. Overall, 152 (69.4%) declared

Knowledge gap about immune checkpoint inhibitors among rheumatologists and medical students: a survey.

Previous studies found that physicians working in developed countries in Europe and in the USA declared insufficient knowledge concerning immune-related adverse events (irAE) following use of immune checkpoint inhibitors (ICI) in cancer treatment. We determined this knowledge gap among rheumatologists and medical students (MS) in Brazil. A web-based structured survey or a direct interview was applied to 1428 board-certified Brazilian rheumatologists and an adapted questionnaire was sent to 840 undergraduate MS attending the last 2 years of Medical Schools in Fortaleza-CE, Brazil, in September 2019. 228 (15.9%) rheumatologists and 145 (17.2%) MS answered the survey; 136 (60%) rheumatologists worked at Institutions with Oncology service. Rheumatologists had 22.6 ± 12.6 years of medical practice, most [116 (50.9%)] worked in private practice and 9 (3.9%) were on training. Fifty-three (23.4%) declared being familiar [40 (17.6%)] or very familiar [13 (5.8%)] with irAE. Almost two-thirds declared having never managed irAE and about a third (38.6%) felt confident in managing such patients. Knowledge among rheumatologists was similar regardless of having more or less than 10 years of practice (P = 0.758). Less than 5% MS declared being familiar with ICI and most have never heard of irAE. There is a large gap concerning knowledge about ICI and irAE among rheumatologists and MS in Brazil. Continuing medical education strategies are needed to improve this knowledge.

Advances in rheumatology practice in Brazil.

Despite resilient inequities, Brazil has seen progressive improvement in health care in the last 25 years. Infectious diseases rendered place to chronic non-communicable diseases as a major cause of death. Existence of traditional schools of medicine and training services in rheumatology helped form a reasonable number of specialists, though irregular distribution due to the economic issues favoring their clustering in major cities. The Brazilian Society of Rheumatology provides continued medical education, helps training rheumatologists, family physicians and other health professionals and has worked to publish national recommendations for the diagnosis and treatment of major rheumatic diseases. Access to medications and health care facilities is provided for most patients, free of direct charge, including biologics. Specialized services for autoimmune and rare diseases, including pediatric rheumatology and autoinflammatory diseases, have improved, particularly in developed centers of the southern best developed parts of the country. A major unmet need is the lack of access to non-pharmacological treatment modalities. In this article, we will summarize some of the strengths and points that need improvement to enhance access to the rheumatological health care in Brazil.

Evaluation of disease activity in a low-income juvenile idiopathic arthritis cohort.

Determine disease activity in a low income juvenile idiopathic arthritis (JIA) cohort. 164 JIA patients from families with less than US$ 4500.00/capita mean annual income followed in Fortaleza-CE, Brazil, were cross-sectionally evaluated between May 2015-April 2016. Mean age was 14 ± 5.1 years (95 female) with 10.31 ± 3.7 years disease duration. Polyarticular category predominated, with 63 (38.4%) patients, followed by 40 (24%) enthesitis-related (ERA), and 36 (22%) oligoarticular. All but 1 out of 84 parents declared less than US$ 10,000.00 annual family income. Eighty-eight (60.7%) were receiving methotrexate and 19 (13%) leflunomide including 12 (63%) using both; 46 (28%) were on biologic DMARD including 20 (43.5%) adalimumab, 17 (41.5) etanercept, 5 (10.8%) tocilizumab, 2 (4.2%) abatacept, and 1 (2.1%) each on infliximab and canakinumab. Mean CHAQ and JADAS27 were 0.36 ± 0.55 and 5.31 ± 8.5, respectively. Thirty-two (20%) out of 159 patients had deformities. A bivariate analysis revealed that polyarticular had more deformities than oligoarticular patients (p = 0.002; OR = 2.389; 95% CI 1.37-4.14). Logistic regression showed no association between high JADAS and family income (p = 0.339; OR = 1.45; 95% CI 0.67-3.31). A general linear model showed significantly lower CHAQ score in patients from families earning more as compared to those earning less than 300.00 US$ monthly (p = 0.002). This study reports JIA disease activity in a low income population. Low income apparently did not influence prognosis given the low mean JADAS27 and CHAQ scores vis-à-vis data from other cohorts.

Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms.

OBJECTIVE: We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models. MATERIALS AND METHODS: Rats received 1 mg zymosan (Zy) or saline intra-articularly. Other groups were subjected to anterior cruciate ligament transection in the right knee, as an osteoarthritis (OA) model, or a sham procedure. Joint pain was assessed using the articular incapacitation and paw-pressure tests. Cell influx and cytokines were measured in joint exudates. TREATMENT: Groups received either SR (30-300 mg/kg per os) or saline. RESULTS: SR dose-dependently and significantly inhibited joint pain in both Zy and OA models, while not altering cell influx. Naloxone administration significantly reversed SR analgesia. SR significantly reduced levels of Interleukin-1ß and tumor necrosis factor-α in Zy arthritis, whereas those of cytokine-induced neutrophil chemoattractant (CINC)-1 were not altered. CONCLUSIONS: SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

Vitamin D levels in juvenile idiopathic arthritis from an equatorial region.

We aimed to describe the serum levels of 25-hydroxyvitamin D (25OHD) in juvenile idiopathic arthritis (JIA) patients living in a low-latitude (3°43'S) region. Fifty JIA patients, 31 (62 %) female, seen between May 2012 and April 2013 in the northeast of Brazil had clinical data and serum collected for determination of 25OHD and parathyroid hormone (PTH) using a chemiluminescent ELISA; 20 age- and sex-matched controls were used for comparison. Mean age was 13.4 ± 4 years. Twenty-five (50 %), 15 (30 %), 4 (8 %), 4 (8 %), and 2 (4 %) patients were of the polyarticular, oligoarticular, systemic, enthesitis-related, and undifferentiated categories, respectively. Mean 25OHD was 31.6 ± 10 and 30.4 ± 5.7 ng/mL in patients and controls (P > 0.05), respectively; PTH was normal in JIA and controls; 25OHD was similar regardless of JIA category, disease activity, or severity measured by JADAS-27, CHAQ, or presence of joint deformities. Twenty-six (52 %), 20 (40 %), and 4 (8 %) patients were considered to have optimal, sufficient, and deficient 25OHD levels, respectively, whereas 11 (52 %) and 10 (48 %) controls had optimal and sufficient 25OHD. Ethnicity, body mass index, seasonal variation, and use of steroids did not influence 25OHD levels. This is the first study on 25OHD levels in JIA patients living in a low-latitude region, showing the lowest prevalence of vitamin D deficiency ever reported. Serum 25OHD was similar in JIA and controls and did not vary regardless of JIA category or severity.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis.

OBJECTIVE: Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. METHODS: Mice received 0.1 mg/25µL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 µL or saline per os (systemic) or 500 µg/25 µL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. RESULTS: MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. CONCLUSION: MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Having chronic back pain did not impact COVID-19 outcome in a low-income population - a retrospective observational study.

INTRODUCTION: Chronic back pain (CBP) is a major cause of years lived with disability. Social inequalities increase the prevalence and burden of CBP. Management of CBP was affected by restricted access to non-pharmacological treatments and outdoor activities during COVID-19 pandemic. OBJECTIVE: To determine the prevalence of CBP among patients with COVID-19 as well as the impact of having CBP in COVID-19 outcome in our low-income population. METHODS: Retrospective cohort of individuals with confirmed COVID diagnosis from May 2020 - March 2021, at Hospital Regional UNIMED (HRU) in Fortaleza, Ceará, Brazil. Data included comorbidities and household income. RESULTS: Among 1,487 patients, 600 (40.3%) were classified as having CBP. Mean age as well as income were similar in CBP and non-CBP groups, with more women in the CBP group. Hypertension and asthma, but not diabetes, were more prevalent in those with CBP. Need for emergency care, hospitalization, and admission to intensive care unit were similar regardless of having CBP. Dyspnea was more common in CBP vs. non-CBP groups, with 48.8% vs. 39.4% percentages, respectively (p = 0.0004). CONCLUSION: Having CBP prior to COVID did not impact the acute clinical outcome of COVID individuals of a low-income population.

Anti-inflammatory and immunomodulatory effect of an extract of Coccidioides posadasii in experimental arthritis.

Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1ß, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.

Montelukast as a treatment for refractory cutaneous lupus: A case series.

INTRODUCTION: There are no drugs specifically approved to treat cutaneous lupus. Inflammatory cells in lupus skin lesions can produce leukotrienes (LT), which promote tissue damage. In addition to hypersensitivity reactions, LT are also associated with cardiovascular diseases and elevated serum LT levels have been linked to worse atherosclerotic disease in lupus. Targeting LT could thus be an alternative to treat lupus. We present 4 cases of cutaneous lupus successfully treated with montelukast (MLK), a Cys-LT antagonist. METHODS: Four consecutive female systemic lupus erythematosus (SLE) patients with refractory skin lesions were treated with MLK (10 mg/d) in the Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará. Skin lesions were scored using Revised Cutaneous LE Disease Area and Severity Index (RCLASI). Relative expression of the 5-lipoxigenase (ALOX5) and 15-lipoxigenase (ALOX15) genes was determined in peripheral blood cells (PBC) from lupus patients and 4 age-matched female controls. RESULTS: All patients experienced improvement of skin lesions measured using RCLASI scores within 2-12 weeks following initiation of MLK. The response was sustained for at least 3 months follow-up and no adverse events were recorded. ALOX5 but not ALOX15 gene expression was significantly (P = 0.0425) increased in PBC from SLE patients vs controls. CONCLUSION: This is the first report of a fast and sustained successful response of cutaneous lupus to MLK. Given its acceptable safety profile, our data encourage development of a randomized trial as an attempt to reposition MLK as a safe, affordable alternative to treat cutaneous lupus.

Biochemical characterization of an in-house Coccidioides antigen: perspectives for the immunodiagnosis of coccidioidomycosis.

The objective of this study was to evaluate the reactivity of an in-house antigen, extracted from a strain of C. posadasii isolated in northeastern Brazil, by radial immunodiffusion and Western blotting, as well as to establish its biochemical characterization. The protein antigen was initially extracted with the use of solid ammonium sulfate and characterized by 1-D electrophoresis. Subsequently, it was tested by means of double radial immunodiffusion and Western blotting. A positive reaction was observed against the antigen by both immunodiagnostic techniques tested on sera from patients suffering from coccidioidomycosis. Besides this, two immunoreactive protein bands were observed and were revealed to be a ß-glucosidase and a glutamine synthetase after sequencing of the respective N-terminal regions. Our in-house Coccidioides antigen can be promising as a quick and low-cost diagnostic tool without the risk of direct manipulation of the microorganism.

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N'N'-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.

Quantitative evaluation of very early cartilage damage in experimental osteoarthritis using scanning electron microscopy.

OBJECTIVE: To describe parametric changes observed using scanning electron microscopy (SEM) in very early stages in posttraumatic osteoarthritis (OA) models in mice. METHODS: Mice (5/group) had their knees subjected to anterior cruciate ligament transection (ACLT), ACLT plus meniscectomy (MNCT) or sham surgery, sacrificed after 3, 7 or 14 days, had the articular cartilage evaluated under optical microscopy using Osteoarthritis Research Society International (OARSI) parameters as well as cartilage thickness, roughness, and a damage index using SEM. RESULTS: Alterations of the cartilage under optical microscopy were not significantly relevant among groups. SEM analysis revealed reduction of femoral and tibial cartilage thickness in ACLT and MNCT groups at 7 and 14 days, with increased cartilage roughness in MNCT group as early as 3 days postsurgery, being sustained up to 14 days. Articular damage index was significantly higher at 14 days post surgery in ACLT and MNCT vs control groups. CONCLUSION: This is the first demonstration of very early quantitative changes in the cartilage of mice subjected to posttraumatic experimental OA using SEM, revealing increased roughness and thickness as early as 3 days post surgery. These changes may be used as early surrogates for later joint damage in experimental OA.

Synergistic effect of antituberculosis drugs and azoles in vitro against Histoplasma capsulatum var. capsulatum.

This study evaluated in vitro interactions of antituberculosis drugs and triazoles against Histoplasma capsulatum. Nine drug combinations, each including an antituberculosis drug (isoniazid, pyrazinamide, or ethambutol) plus a triazole (itraconazole, fluconazole, or voriconazole), were tested against both growth forms of H. capsulatum. Stronger synergistic interactions were seen in isoniazid or pyrazinamide plus triazoles for the mold form and ethambutol plus voriconazole for the yeast-like form. Further studies should evaluate these combinations in vivo.

Tumor necrosis factor inhibitors prevent structural damage in hips in ankylosing spondylitis-time to reconsider treatment guidelines? A case series and review of literature.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common "non-spinal" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.

Translation, cultural adaptation and reproducibility of a Portuguese version of the Functional Index for Hand OsteoArthritis (FIHOA).

BACKGROUND: The Functional Index for Hand Osteoarthritis (FIHOA) is a simple, reliable, and reproducible specific instrument to evaluate hand OA that can be applied both in clinical practice and research protocols. In order to be used in Brazil, FIHOA has to be translated into Portuguese, culturally adapted and have the reliability of the translated FIHOA version tested, which is the purpose of this study. METHODS: The FIHOA was translated into Brazilian Portuguese and administered to 68 patients with hand OA recruited between May 2019 and February 2020. The test-retest was applied to 32 patients and the reliability was assessed using Spearman's correlation coefficient and intraclass correlation coefficient (ICC). The internal consistency reliability was evaluated using Cronbach's alpha. External construction validity was assessed using the Spearman's correlation test between FIHOA and pain, assessed with a Visual Analogue Scale (VAS), the Cochin Hand Functional Scale (CHFS) and Health Assessment Questionnaire (HAQ). RESULTS: The 30 participants that initially answered the translated version of the FiHOA did not report difficulties in understanding or interpreting the translated version. The test-retest reliability for the total score was strong (r = 0.86; ICC = 0.89). Mean differences (1.37 ± 0.68) using Bland Altman's analysis did not significantly differ from zero and no systematic bias was observed. Cronbach's alpha was also high (0.89) suggesting a strong internal coherence in the test items. There were also correlations between FIHOA and the CHFS (r = 0.88), HAQ (r = 0.64) and pain in the hands both at rest (r = 0.55) and in motion (r = 0.44). CONCLUSION: The translation of the FIHOA into Brazilian Portuguese proved a valid instrument for measuring the functional capacity of patients with hand OA who understand Brazilian Portuguese.