A experiência da vida real com complicações cardiovasculares na primeira dose de fingolimode

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.Fingolimode é um tratamento novo e eficaz para esclerose múltipla (EM). A administração desta droga requer atenção especial para a primeira dose, uma vez que eventos adversos cardiovasculares podem ser observados nas seis horas iniciais da ingestão de fingolimode. O presente estudo consistiu de uma revisão de dados cardiovasculares de 180 pacientes com EM ao receberem a primeira dose de fingolimode. A taxa de bradicardia nestes pacientes foi maior do que aquele observada em estudos clínicos que tem critérios de inclusão muito rigorosos para seleção de pacientes. Menos de 10% dos casos necessitou de atenção especial, mas não houve casos fatais. Todos os pacientes exceto por um continuaram o tratamento após esta dose inicial. Este é o primeiro relato de dados de administração de fingolimode na vida real de pacientes brasileiros com EM, e um dos poucos trabalhos com estas características no mundo.Universidade Metropolitana de Santos Departamento de NeurologiaUniversidade Positivo Departamento de NeurologiaUniversidade Federal do Paraná Departamento de NeurologiaUniversidade Estadual de Campinas Departamento de NeurologiaUniversidade Federal de Juiz de Fora Departamento de NeurologiaHospital de Clínicas de Porto Alegre Departamento de NeurologiaPontifícia Universidade Católica Sorocaba Departamento de NeurologiaClínica Holus MedServiceHospital Beneficência Portuguesa de São Paulo Departamento de NeurologiaCentro Hospitalar Unimed Departamento de NeurologiaUniversidade Federal Fluminense Departamento de NeurologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de NeurologiaHospital de Base do Distrito Federal Departamento de NeurologiaInstituto de Neurologia de Curitiba Departamento de NeurologiaUNIFESP, Depto. de NeurologiaSciEL

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis.

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.72712-

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Unfavorable Outcomes During Treatment Of Multiple Sclerosis With High Doses Of Vitamin D.

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Alternatives For Reducing Relapse Rate When Switching From Natalizumab To Fingolimod In Multiple Sclerosis.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Multiple sclerosis starting before the age of 18 years: the Brazilian experience

Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt