Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis

Objectives To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA

Characteristics and outcomes of people with gout hospitalized due to COVID-19: data from the COVID-19 Global Rheumatology Alliance Physician - reported registry

Objective. To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. Methods. Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021,were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describethe demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. Results. One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease(28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) ofthe cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death wasreported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion. This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity

Efficacy and safety of tocilizumab for polyarticular-course juvenile idiopathic arthritis in the open-label two-year extension of a phase III trial

Objective. To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods. Patients ages 2–17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] 1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure. Results. Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years. Conclusion. Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported

O novo fado: uma leitura transcultural

Dissertação de mestrado em Literatura e Cultura ComparadasEste projeto tratará o fado de Lisboa enquanto fenómeno cultural, inserindo-se, portanto, no âmbito dos estudos culturais. A sua história será abordada e a sua evolução questionada, em contraste com os métodos sociológicos ou de antropologia social, que adotam uma posição essencialista. Para isso, esta dissertação analisará os movimentos de nacionalização e posterior internacionalização do género musical, argumentando que ao sair das típicas casas de fado dos bairros tradicionais de Lisboa para a rádio, discografia e teatros nacionais, o fado se torna uma marca comercial do país inteiro (nation branding) e espelha todo o sentimento de um povo (encontrando previamente, no séc. XIX, a sua narrativa fundacional no romance de Maria Severa com o Conde de Vimioso). Semelhante processo foi o do Flamengo gitano e andaluz (alicerçado pelo mito de Carmen), que se tornou símbolo da cultura espanhola. A construção da identidade nacional portuguesa através do diálogo com o fado enquanto quintessência do país, fundeada mediante o conceito romântico dos irmãos Schlegel, permite uma idealização etnográfica, política e social do género como sendo expressão natural da ‘alma do povo’ (Volksseele ou Volksgeist). A partir da análise crítica da ‘nacionalização’ do fado, a nossa leitura transcultural incidirá sobre a receção do fado no estrangeiro e sobre a contaminação por outros géneros e culturas, chegando a questionar o conceito de ‘pureza’ subjacente à idealização do fado como signo da identidade do país e do povo, entendidos de uma forma essencial e homogénea. A leitura transcultural do género, inspirada por Wolfgang Welsch e outros, permitirá uma abordagem de percursos de artistas do ‘novo fado’, tais como Mísia, Cristina Branco, Mariza e a banda a Naifa, o que constituirá o peso maior da investigação, no âmbito de uma cultura ‘glocal’.This project will attempt to examine the fado of Lisbon as a cultural phenomenon and is therefore part of the broad area of cultural studies. The history of fado will be studied, and its evolution questioned in contrast with sociological or social anthropological methods which adopt an essentialist approach. In this sense, this dissertation will analyze fado’s nationalizing and internationalizing processes, arguing that when fado leaves its typical houses in the traditional neighborhoods of Lisbon into the national radio, discography and theatres, it becomes a commercial brand for the entire country (nation branding), symbolizing its people’s soul (and finding its foundational narrative in Maria Severa and Conde de Vimioso’s love affair in the 19th Century). A similar process occurred with the flamenco Gitano and andaluz (justified by the myth of Carmen), which has become a symbol of Spanish culture. The construction of a Portuguese national identity through the dialogue with fado as the country’s quintessence, backed up by the recourse to the romantic concept of the Schlegel brothers, allows for an ethnographical, political and social idealization of the genre as the natural expression of the ‘soul of the people’ (Volksseele ou Volksgeist). Through the analysis of the nationalization of fado, our transcultural reading will also look at its reception abroad and its contamination by other genres and cultures. This will allow for the questioning of the concept of ‘purity’ that underlies fado’s idealization as a sign of the people and the country’s identity, which are still understood essentially and homogeneously. Inspired by Wolfgang Welsch and other authors, the transcultural reading will analyze some of the ‘novo fado’ artists’ careers: Mísia, Cristina Branco, Mariza and the band A Naifa. This constitutes the major part of this dissertation, within a ‘glocal’ culture

Effects of participating in a research project during the covid-19 pandemic on medical students’educational routines and mental health : protocol for a web-based survey study

Background: The COVID-19 pandemic has resulted in social isolation, which has a potential negative impact on the educational routines (eg, the suspension of face-to-face appointments) and mental health of medical students. The Mario Pinotti II (MPII) study is a 24-week observational study that conducted scheduled telephone calls every 2 weeks to verify the occurrence of COVID-19 in patients with rheumatic diseases on chronic hydroxychloroquine therapy (from March 29, 2020, to September 30, 2020). The effects of voluntarily participating in a research project (ie, one that involves interactions via telephone contact with patients, professors, rheumatologists, and colleagues) on the daily lives and mental health of medical students requires evaluation. Objective: As medical students are professionals in training and have a high level of responsibility in terms of handling the emotional and physical aspects of several diseases, this study aims to evaluate the impacts of the COVID-19 pandemic and participation in the MPII study on the educational routines and mental health of medical students. Methods: A web-based survey was carried out to perform a cross-sectional comparative assessment of medical students who participated in the MPII study and their colleagues who were not involved in the MPII study. Participants from both groups were matched based on sex, age, and medical school. The web questionnaire was developed by a panel composed of graduate medical students, rheumatologists, medical school professors, and a psychology professor. The questionnaire included details on demographic and life habits data and evaluated participants' impressions of the MPII study and the impact of the COVID-19 pandemic on their educational routines and medical training. In addition, depression, anxiety, and stress were evaluated using the Brazilian version of the Depression, Anxiety, and Stress Scale (DASS)-21, and currently, the DASS-21 scores are grouped as those that indicate a low, moderate, or high risk of mental distress. This project was approved by the Federal University of São Paulo Ethics Committee (CAAE: 34034620.0.0000.5505). Results: Data were collected from both medical student groups from July 20 to August 31, 2020. Data extraction was completed in September 2020. The data analysis is ongoing. We expect the results to be published in the first semester of 2021. Conclusions: This study will provide insight into the effects of participating in a research project on depression, anxiety, and stress, which will be determined by applying the DASS-21 to a large sample of Brazilian undergraduate medical students. We will also evaluate the impact of the COVID-19 pandemic on medical students’ educational routines and medical training

Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis : data from a large real-life cohort

The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017

Postoperative pain after endodontic treatment of necrotic teeth submitted to large apical preparation using oscillatory kinematics

Regardless of the technique applied for chemomechanical preparation, postoperative pain is a very relevant matter in endodontics. Objective: To evaluate postoperative pain after endodontic treatment of necrotic teeth submitted to large apical preparatio

Estatura e maturac¸ão sexual em meninas com artrite idiopática juvenil

Objective: To evaluate height, sexual maturation, and the difference between final and expected height in girls with juvenile idiopathic arthritis and no glucocorticoid treatment for at least six months, as compared to a group of healthy girls. Methods: This cross-sectional study involved 44 girls with juvenile idiopathic arthritis, diagnosed according to the International League of Associations for Rheumatology criteria, and 59 healthy controls aged between 8 and 18 (incomplete) years with no comorbid chronic diseases. Demographic data were collected from all participants, and disease and treatment variables were compiled for the patient group. Anthropometric measurements were converted into Z-scores based on World Health Organization standards. Sexual maturation was classified according to Tanner stages. Results: Body mass index and height Z-scores were lower in girls with juvenile idiopathic arthritis as compared to control participants. These values differed significantly in Tanner stage II. Three (6.8%) girls with juvenile idiopathic arthritis had height-for-age Z-scores <−2 (short stature). Girls with polyarticular juvenile idiopathic arthritis and higher cumulative glucocorticoid doses were significantly more likely to present with short stature. The percentage of prepubertal girls in the juvenile idiopathic arthritis group was significantly higher than that observed in the control group, (p = 0.012). Age of menarche, adult height, and the difference between actual and expected height did not differ between groups. Conclusion: These findings suggest that even six months after the suspension of glucocorticoid treatment, children with polyarticular/systemic juvenile idiopathic arthritis subtypes are still susceptible to low height and delayed puberty.Objetivo: Avaliar a estatura, maturac¸ão sexual e a diferenc¸a entre a estatura final e a esperada em meninas com artrite idiopática juvenil (AIJ) sem tratamento com glicocorticoides por pelo menos seis meses, em comparac¸ão com um grupo de meninas saudáveis. Métodos: Este estudo transversal avaliou 44 meninas com artrite idiopática juvenil, diagnosticadas de acordo com os critérios da International League of Associations for Rheumatology e 59 controles saudáveis, entre oito e 18 anos (incompletos) sem comorbidades por doenc¸as crônicas. Os dados demográficos foram coletados de todos os participantes e as variáveis de doenc¸a e tratamento foram compiladas para o grupo de pacientes. As medidas antropométricas foram convertidas em escores-z com base nos padrões da Organizac¸ão Mundial da Saúde. A maturac¸ão sexual foi classificada de acordo com os estágios de Tanner. Resultados: Índice de massa corporal e escores-z de estatura foram menores em meninas com artrite idiopática juvenil em comparac¸ão com os participantes-controle. Esses valores diferiram significativamente no estágio II de Tanner. Três (6,8%) meninas com artrite idiopática juvenil tinham escores-z de estatura para idade < -2 (baixa estatura). Meninas com artrite idiopática juvenil poliarticular e doses cumulativas de glicocorticoides foram significativamente mais propensas a apresentar baixa estatura. A porcentagem de meninas pré-púberes no grupo artrite idiopática juvenil foi significativamente maior do que a observada no grupo controle (p = 0,012). A idade da menarca, a estatura adulta e a diferenc¸a entre a estatura real e a esperada não diferiram entre os grupos. Conclusão: Esses achados sugerem que, mesmo após seis meses da suspensão do tratamento com glicocorticoides, as crianc¸as com os subtipos poliarticular/sistêmico de AIJ ainda são suscetíveis a baixa estatura e atraso na puberdade