Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate

Objectives Long-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment. Methods Children aged 4-17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, = 6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis). Conclusions Through 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate

Translation and validation of the Transition Readiness Assessment Questionnaire (TRAQ)

Objective: To translate and validate the Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire in a population of adolescents and young adults with chronic rheumatologic disorders. This questionnaire evaluates the patient's readiness for making the transition from the pediatric health service to adult care. Methods: The four‐phase methodology for the translation and validation of generic questionnaires was followed, including translation, back‐translation, pilot testing and clinical validation of the final tool. The confirmatory factor analysis was used for clinical validation and the Cronbach's alpha coefficient was used to assess the overall internal consistency of the final tool. Results: A total of 150 patients with a mean age of 17.0 years (SD = 2.2 years, range 14–21 years) were enrolled for the final tool validation. Of those, 71 patients had juvenile systemic lupus erythematosus (47.3%), 64 had juvenile idiopathic arthritis (42.7%), and 15 had juvenile dermatomyositis (10%). During the confirmatory factor analysis, the dimension “Talking with providers” consisting of two questions, was considered as not fitting the translated questionnaire due to a very high ceiling effect and was therefore excluded. All other translated items favorably contributed to the overall consistency of the final tool; removing that dimension did not result in a substantial increase in Cronbach's alpha, which was 0.776. Conclusions: The Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire was validated in a population of transitional patients with chronic rheumatologic disorders, after one dimension from the original questionnaire was excluded. It is a non‐specific disease questionnaire; thus, it can be used to evaluate the transition readiness of Brazilian patients with other chronic diseases. Resumo: Objetivo: Traduzir para o português brasileiro e validar o Questionário de Avaliação do Preparo para a Transição em uma população de adolescentes e adultos jovens com doenças reumáticas crônicas. Este questionário avalia o preparo do paciente para realizar a transição do serviço de saúde pediátrico para a assistência ao adulto. Métodos: Seguimos a metodologia de quatro etapas para a tradução e validação de questionários genéricos que inclui tradução, retrotradução, teste piloto e validação clínica do instrumento final. Utilizamos Análise Fatorial Confirmatória e Coeficiente Alfa de Cronbach para testar a validade do instrumento e sua consistência interna. Resultados: Responderam ao questionário traduzido e adaptado 150 pacientes. A média de idade foi de 17,0 anos (DP = 2,2 anos, variação 14‐21 anos). Tinham o diagnóstico de lúpus eritematoso sistêmico juvenil 71 pacientes (47,3%), 64 (42,7%) artrite idiopática juvenil e 15 (10%) dermatomiosite juvenil. Durante a análise fatorial confirmatória, a dimensão “Falando com a Equipe Médica” contendo duas questões teve que ser removida devido à presença de expressivo efeito teto. Todas as outras questões restantes contribuíram favoravelmente para aumentar a consistência interna do questionário, obteve‐se um Coeficiente Alfa de Cronbach de 0,776. Conclusões: O Questionário de Avaliação do Preparo para a Transição na sua versão em português brasileiro pode ser validado em uma população de pacientes com doenças reumáticas crônicas em transição, com a exclusão de uma dimensão do questionário original. Por ser um questionário não específico para doenças reumáticas, poderá ser utilizado para avaliar o preparo para a transição de outros pacientes brasileiros com doenças crônicas. Keywords: Transition readiness tool, TRAQ, Brazil, Rheumatology, Adolescent health services, Research in health services, Palavras‐chave: Avaliação do preparo para a transição, TRAQ, Brasil, Reumatologia, Serviços de saúde do adolescente, Pesquisa em serviços de saúd

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate

OBJECTIVES: Long-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment. METHODS: Children aged 4-17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1). RESULTS: Of 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart failure-related AEs, demyelinating disease, lupus-like syndrome, malignancies, tuberculosis or deaths were reported. JIA ACR 30/50/70/90 responses and JADAS27 LDA were achieved in 66% to 96% of patients at week 104, and 63 (37%) patients achieved clinical remission (JADAS27 ID sustained for ≥6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis). CONCLUSIONS: Through 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.status: publishe

Simulation-Based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM)-A Prospective Single-Arm Multicenter Trial

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2-3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the door-to-needle time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three STREAM multipliers from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2-3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings

Float, explode or sink: postmortem fate of lung-breathing marine vertebrates

What happens after the death of a marine tetrapod in seawater? Palaeontologists and neontologists have claimed that large lung-breathing marine tetrapods such as ichthyosaurs had a lower density than seawater, implying that their carcasses floated at the surface after death and sank subsequently after leakage of putrefaction gases (or ‘‘carcass explosions’’). Such explosions would thus account for the skeletal disarticulation observed frequently in the fossil record. We examined the taphonomy and sedimentary environment of numerous ichthyosaur skeletons and compared them to living marine tetrapods, principally cetaceans, and measured abdominal pressures in human carcasses. Our data and a review of the literature demonstrate that carcasses sink and do not explode (and spread skeletal elements). We argue that the normally slightly negatively buoyant carcasses of ichthyosaurs would have sunk to the sea floor and risen to the surface only when they remained in shallow water above a certain temperature and at a low scavenging rate. Once surfaced, prolonged floating may have occurred and a carcass have decomposed gradually. Our conclusions are of significance to the understanding of the inclusion of carcasses of lung-breathing vertebrates in marine nutrient recycling. The postmortem fate has essential implications for the interpretation of vertebrate fossil preservation (the existence of complete, disarticulated fossil skeletons is not explained by previous hypotheses), palaeobathymetry, the physiology of modern marine lung-breathing tetrapods and their conservation, and the recovery of human bodies from seawater

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None