Consulta de enfermagem de adolescentes: um recorte importante do cuidado prestado por enfermeiros em um Estado brasileiro

Objetivo: el cuidado de los adolescentes con o sin enfermedad crónica debe ser completo, estandarizado y centrado en las demandas individuales y en el proceso de transición a la atención para adultos y la adherencia al tratamiento. Este estudio tuvo como objetivo caracterizar los cuidados prestados por el personal de enfermería del estado de São Paulo que trabaja con adolescentes. Método: se trata de un estudio transversal y descriptivo sobre los cuidados prestados a los adolescentes por el personal de enfermería de São Paulo, a partir de las respuestas a un cuestionario autoadministrado, disponible en la herramienta REDCap entre agosto de 2018 y octubre de 2019. Resultados: los participantes respondieron a 1.632 cuestionarios. Solo el 38% del personal de enfermería trabaja con adolescentes, el 11,2% de forma exclusiva. Los profesionales se dividieron según la duración media de la experiencia profesional en los grupos A y B (≤5 años y >5 años). La drogadicción (p=0,01) y el trabajo con un equipo multidisciplinar (p=0,04) fueron significativamente más reportados en el grupo B. El seguimiento rutinario (p=0,02) y las preguntas sobre violencia sexual o física (p=0,03) fueron significativamente más realizadas por los profesionales del grupo A. Conclusión: este estudio identificó la necesidad de un protocolo de atención que pueda ser replicado a gran escala y que incluya el tratamiento y las particularidades de los adolescentes para mejorar la adherencia y la transición a la atención de adultos.Objective: the care of adolescents with or without a chronic disease must complete, standardized and focused on individual demands and the transition process to adult care and adherence to treatment. This study aimed to characterize the care provided by nurses from the state of São Paulo who work with adolescents. Method: this is a cross-sectional and descriptive study on the care provided to adolescents by nurses in São Paulo, based on the answers to a self-administered questionnaire, available in the REDCap tool between August 2018 and October 2019. Results: participants answered 1632 questionnaires. Only 38% of nurses work with adolescents, 11.2% exclusively. Professionals were divided according to the median length of professional experience in groups A and B (≤5 years and >5 years). Drug addiction (p=0.01) and working with a multidisciplinary team (p=0.04) were significantly more reported in group B. Routine follow-up (p=0.02) and questioning about sexual or physical violence (p=0.03) were significantly more performed by professionals from group A. Conclusion: this study identified the need for a care protocol that can be replicated on a large scale and that includes the treatment and the particularities of adolescents to improve adherence and the transition into adult care.Objetivo: o cuidado de adolescentes com ou sem doença crônica deve ser completo, padronizado e focado nas demandas individuais e no processo de transição para a assistência ao adulto e adesão ao tratamento. Este estudo teve como objetivo caracterizar a assistência prestada por enfermeiros do estado de São Paulo que atuam com adolescentes. Método: trata-se de um estudo transversal e descritivo sobre a assistência prestada a adolescentes por enfermeiros de São Paulo, a partir das respostas a um questionário autoaplicável, disponível no instrumento REDCap entre agosto de 2018 e outubro de 2019. Resultados: os participantes responderam a 1632 questionários. Apenas 38% dos enfermeiros trabalham com adolescentes, e 11,2% deles de forma exclusiva. Os profissionais foram divididos de acordo com a mediana de tempo de experiência profissional nos Grupos A e B (≤ 5 anos e > 5 anos). A dependência de drogas (p=0,01) e o trabalho com uma equipe multidisciplinar (p=0,04) foram significativamente mais relatados no Grupo B. O acompanhamento rotineiro (p=0,02) e o questionamento sobre violência sexual ou física (p=0,03) foram significativamente mais realizados pelos profissionais do Grupo A. Conclusão: este estudo identificou a necessidade de um protocolo de assistência que possa ser replicado em larga escala e que inclua o tratamento e as particularidades dos adolescentes para melhorar a adesão e a transição para o cuidado do adulto

Prospective cohort studies to evaluate the safety and immunogenicity of the 2013, 2014, and 2015 seasonal influenza vaccines produced by Instituto Butantan

Annual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Fortyseven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA)

Characterization of the profile of professional capacitation program for nurses in a teaching hospital complex

No âmbito hospitalar o número de enfermeiros é significativo, atuando desde o âmbito assistencial até cargos de chefia e participação em assessorias. Todavia, para essa atuação, o conhecimento não é definitivo, sendo necessário que o profissional desenvolva aprendizagem contínua e atualizada. A presente pesquisa qualitativa teve como objetivo geral caracterizar um perfil de capacitação profissional do enfermeiro de um Complexo Hospitalar de ensino a partir da percepção das Diretoras de Divisão de Enfermagem dos Institutos que compõem o pólo central do Complexo Hospitalar do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e como objetivos específicos: identificar a percepção das colaboradoras acerca do perfil de capacitação dos enfermeiros; conhecer as propostas que orientam essa capacitação; e analisar os elementos institucionais necessários para a efetivação desse processo. Optou-se pelo método do Estudo de Caso, cuja flexibilidade permite confirmar, modificar, ou ampliar o conhecimento sobre o objeto que estuda, contribuindo assim para a construção teórica do respectivo domínio do conhecimento. Foram colaboradoras do estudo as seis Diretoras de Divisão de Enfermagem do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e suas substitutas, totalizando doze colaboradoras. A coleta de dados foi realizada por meio de entrevistas semiestruturadas, após aprovação do estudo pelo Comitê de Ética em Pesquisa da EEUSP e da Comissão de Ética para Análise de Projetos de Pesquisa - CAPPesq do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e assinatura do Termo de Consentimento Livre e Esclarecido pelas colaboradoras. Para análise dos dados foi adotada a técnica da Análise de Conteúdo de Bardin, que possibilitou o resgate das Categorias Política Institucional, Política de Gerenciamento de Recursos Humanos e Elementos Intervenientes do Processo de Capacitação Profissional do Enfermeiro. Os resultados mostraram que não há uma política institucional formalizada para a capacitação do enfermeiro em todos os Institutos; que a contratação de enfermeiros recém-formados e a questão salarial são elementos dificultadores para a capacitação; a contrapartida das instituições de ensino aparece como um recurso para atender às necessidades de capacitação do enfermeiro; dois Institutos não possuem Serviço de Educação Continuada; o perfil do profissional demandado, na concepção semelhante das colaboradoras, é de um profissional com postura ética, conhecimento técnico-científico, capacidade de gerenciar sua equipe, assíduo, pontual e comprometido com a Instituição. A Coordenação das Atividades de Enfermagem (CAENF), composta pelas diretoras de Divisão de Enfermagem dos Institutos, tem entre seus objetivos a proposta de montar um grupo/recurso para a capacitação e desenvolvimento do pessoal. Dessa forma depreende-se que existe empenho dos enfermeiros e das chefias de enfermagem no desenvolvimento da capacitação profissional. Entretanto, essa disposição não tem sido elemento suficiente para superar as dificuldades de ordem política e econômica que perpassam um Complexo Hospitalar PúblicoIn a hospital complex is significant the number of nurses working to assist people and also in the leadership jobs and participating in advisory tasks. However, for this type of work, knowledge is not definitive and the professional needs to develop continuous and updating learning. The present qualitative research had the general objective to characterize the profile of the professional capacitating program for nurses in a Teaching Hospital Complex, based on the six directors´ and their six substitutes\' perception of the Nursing Division of the Institutes which take part of the central pole of the Hospital Complex of the Clinicas Hospital of the Faculty of Medicine of the São Paulo University (USP), totaling 12 collaborators. The specific objectives were to identify the collaborators\' perception about the nurse\'s profile in the capacitating program and to know the proposals which oriented this process. The Study of a Case was the method of choice whose flexibility allowed to confirm, modify or to improve the knowledge on the studied object thus contributing for the theoretical construction of the respective knowledge domain. Data collection was carried out by means of semi-structured interviews after approval of the study made by the Ethic Committee in Research of the Nursing School at USP and of the Ethic Committee for Analysis of Research Projects of the Clinicas Hospital of the Faculty of Medicine of the São Paulo University and also the signature of the Free Informed Consent by the collaborators. For analysis of data, the Bardin\'s Content Analysis was used which allowed to rescue the Institutional Policy Categories, Policy of Human Resources Management and the Intervening Elements of the Nurse\'s Professional Capacitating Program. The results showed that there is no formal institutional policy to capacitate the nurse in all the Institutes; employment of fresh graduate nurses and the remuneration policy are difficult elements in the capacitating program. The counterpart of the teaching institutions appears as a resource to assist the needs of the nurse capacitating program; two Institutes do not have a Continuing Education Program; the demanding profile according to the similar conception of the collaborators is a professional with ethic posture, scientifictechnical knowledge, and ability to deal with the team, assiduous, punctual and engaged with the Institution. The Coordination of the Nursing Activities composed by the directors of the Nursing Division of the Institutes aims to create a group/resource to capacitate and develop the personnel into the institution. Thus, we concluded that there is an effort by the nurses and nursing leadership to professional capacitate their staff, but this effort has not been a sufficient element to surpass their economic and political difficulties inherent to a Public Hospital Comple

Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study

Introdução: A reativação do vírus latente da varicela-zoster ocasiona infecção por herpes zoster tanto em pacientes hígidos quanto em portadores de doenças crônicas e autoimunes, como lúpus eritematoso sistêmico juvenil (LESJ). As informações sobre infecção por herpes zoster (HZ), seus fatores de risco e desfecho no LESJ são limitadas devido à pequena representação desta complicação em publicações anteriores, e revela a necessidade de mais estudos visando contribuir para o melhor cuidado aos pacientes. Objetivos: Avaliar a prevalência de infecção por HZ em uma população expressiva de pacientes com LESJ, e sua possível associação com dados clínicos, demográficos, manifestações clínicas, alterações laboratoriais, atividade/dano cumulativo da doença, tratamento e evolução. Métodos: Estudo de coorte multicêntrico retrospectivo realizado em 10 serviços de Reumatologia Pediátrica do Grupo Brasileiro de Lúpus que incluiu 852 pacientes com LESJ. Os pacientes foram divididos em dois grupos: pacientes que tiveram infecção por HZ (avaliados durante episódio da infecção por herpes zoster) e pacientes sem infecção por HZ (avaliados na última consulta). Resultados: A frequência de infecção por herpes zoster foi 14,1% nos pacientes com LESJ, enquanto neuralgia pós-herpética e recorrência foram observadas em 5% dos pacientes. Ocorreu hospitalização em 61% dos pacientes e infecção bacteriana secundária em 13% dos pacientes. Quanto ao tratamento, 94% dos pacientes com LESJ recebeu aciclovir via intravenosa ou oral ao diagnóstico de infecção por HZ e nenhum deles teve complicação oftalmológica nem evoluiu para óbito. Após correção de Holm-Bonferroni para múltiplas comparações, duração da doença (1,58 vs. 4,41 anos, p<0,0001) e idade atual (13,9 vs. 17,0 anos, p < 0,0001) foram significantemente menores nos pacientes com infecção por HZ comparados aos pacientes sem esta complicação. As frequências de nefrite (37% vs. 18%, p < 0,0001), linfopenia (32% vs. 17%, p < 0,0001), hipertensão arterial (27% vs. 13%, p=0,001) e febre (35,5% vs. 5%, p < 0,0001), foram significantemente maiores nos pacientes com infecção por HZ. As medianas do score de atividade da doença/SLEDAI-2K [6,0 (0-35) vs. 2 (0-45), p < 0,0001], VHS [30 (3-120) vs. 18 (1-135) mm/1a hora, p < 0,0001] e PCR [3,05 (0-103) vs. 0,70 (0-364)mg/dL, p < 0,0001] foram significantemente maiores nos pacientes com infecção por HZ. Quanto ao tratamento, frequências do uso de prednisona (97% vs. 77%, p < 0,0001) e ciclofosfamida (20% vs. 5%, p < 0,0001) foram significantemente maiores nos pacientes com infecção por HZ, assim como medianas da dose atual de prednisona [20 (3 - 80) vs. 12,5 (1- 90) mg/dia, p<0,0001] e em mg/kg/dia [0,44 (0,5 - 3,8) vs. 0,24 (0,02 - 3,0), p < 0,0001]. A regressão logística mostrou quatro variáveis independentes associadas à infecção por HZ: duração da doença menor de 1 ano [OR 2.893 (IC 1.821-4.597), p < 0.0001], linfopenia < 1,500/mm3 [OR 1.931 (IC 1.183-3.153), p=0.009], uso de prednisona [OR 6.723 (IC 2.072-21.815), p=0.002] e uso de ciclofosfamida [OR 4.060 (IC 2.174-7.583), p < 0.0001]. Conclusões: A infecção por HZ foi evidenciada em 14% dos pacientes com LESJ. Este foi o primeiro estudo que identificou atividade da doença e tratamento do LESJ como principais fatores associados para infecção por HZ nos pacientes, que apresentou-se com distribuição típica dermatomal, baixa taxa de recorrência e complicaçõesIntroduction: The latent varicella-zoster virus reactivation causes herpes zoster infection in healthy patients and patients with chronic and autoimmune diseases, such as childhood-onset systemic lupus erythematosus (cSLE). However, information about herpes zoster infection (HZI), risk factors and outcome in cSLE are limited due to the small representation of this complication in previous studies, and reveals the need for more studies to driving better treatments to affected patients. Objective: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory, treatment and outcome. Methods: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services in São Paulo State, Brazil and included 852 cSLE patients. Patients were divided in two groups: patients with HZI (evaluated at the first HZI episode) and patients without HZI (evaluated at the last visit). Results: The frequency of HZI in cSLE patients was 14%. Hospitalization occurred in 61% and secondary bacterial infection in 13%. Intravenous or oral aciclovir was administered in 94% cSLE patients at HZI diagnosis. None of them had ophthalmic complication and death. Postherpetic neuralgia and recurrence rate occurred in 5%. After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs. 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs. 18%, p < 0.0001), lymphopenia (32% vs. 17%, p < 0.0001) prednisone (97% vs. 77%, p < 0.0001), cyclophosphamide (20% vs. 5%, p < 0.0001) and SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001] were significantly higher in the former group. The median activity score of disease / SLEDAI-2K [6.0 (0-35) vs. 2 (0-45), p < 0.0001], ESR [30 (3-120) vs. 18 (1-135) mm/1st hour, p < 0.0001] and PCR [3.05 (0-103) vs. 0.70 (0-364) mg/dL, p < 0.0001] were significantly higher in patients with HZ infection. As for treatment, the frequency of prednisone use (97% vs. 77%, p <0.0001) and cyclophosphamide (20% vs. 5%, p < 0.0001) were significantly higher in patients with HZI, as well as the medians of the current dose of prednisone [20 (3-80) vs. 12.5 (1- 90) mg/day, p < 0.0001] and in mg/kg/day [0.44 (0.5 to 3.8) vs. 0.24 (0.02 to 3.0), P < 0.0001]. Logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year [OR 2.893 (CI 1.821-4.597), p < 0.0001], lymphopenia < 1,500/mm3 [OR 1.931 (CI 1.183-3.153), p=0.009], prednisone [OR 6.723 (CI 2.072-21.815), p=0.002] and cyclophosphamide use [OR 4.060 (CI 2.174-7.583), p < 0.0001]. Conclusion: HZI was identified in 14% of cSLE population. This was the first study that identified disease activity and treatment of cSLE as main factors associated to HZI, that presented as an early viral infection with a typical dermatomal distribution, low rate of recurrence and complication

Impacto na saúde mental de enfermeiros pediátricos: um estudo transversal em hospital pediátrico terciário durante a pandemia de COVID-19

Objetivo: evaluar los problemas de salud mental en enfermerospediátricos durante la pandemia del coronavirus 2019. Método:estudio transversal realizado con enfermeros pediátricos del Institutoda Criança e do Adolescente mediante una encuesta de autoevaluaciónen línea sobre la práctica clínica y el impacto en la salud mental durantela pandemia de COVID-19. Se evaluaron escalas de autoevaluaciónvalidadas para ansiedad, depresión y burnout. Resultados: respondieron107/298 (36%) de los enfermeros, de los cuales 90% eran del sexofemenino, la mediana de edad actual fue de 41 (23-64) años, 68%trabajaban con adolescentes, 66% trabajaban en primera línea. Burnout,ansiedad y depresión moderada/grave ocurrieron en 65%, 72% y 74%de los enfermeros, respectivamente. Falta de protocolo de tratamientoestandarizado en las enfermerías (27% vs. 10%, p=0,049), depresiónmoderada/grave (74% vs. 16%, p=0,002) y burnout (82% vs. 58%,p=0,01) fueron significativamente mayores en enfermeros pediátricoscon ansiedad en comparación con enfermeros sin esta condición. Losenfermeros pediátricos que trabajaban con adolescentes presentaronmayor frecuencia de burnout en comparación con los que no trabajabancon adolescentes (77% vs. 32%, p=0,0001). El análisis multivariadoreveló que el adecuado cumplimiento de la cuarentena aumentó4,6 veces la presencia de ansiedad [OR 4.6(IC 1,1-20,2), p=0,04].Conclusión: La mayoría de los enfermeros pediátricos trabajaban enla primera línea de la COVID-19, en condiciones precarias, trabajandocon un equipo reducido y enfrentando importantes pérdidas de ingresos.La ansiedad actual fue un tema relevante y el burnout también fueuna condición mental importante para estos profesionales, reforzandola cultura del buen trabajo en equipo, las prácticas colaborativas y laatención psicológica/psiquiátrica.Objective: to assess mental health issues in pediatric nurses duringcoronavirus pandemic in 2019. Method: cross-sectional study wasconducted with pediatric nurses at the Instituto da Criança e doAdolescente based on online self-rated survey about clinical practiceand mental health impact during COVID-19 pandemic. Validatedself-reported scales for anxiety, depression and burnout were usedfor assessing these professionals. Results: 107/298 (36%) nursesanswered, 90% were female, median age was 41(23-64) years,68% worked with adolescents, 66% in frontline. Burnout, anxietyand moderate/severe depression occurred in 65%, 72% and 74%,respectively. Lack of standardized treatment protocol for nurses(27%vs.10%, p=0.049), moderate/severe depression (74% vs. 16%,p=0.002) and burnout (82% vs. 58%, p=0.01) were significantlyhigher in pediatric nurses with anxiety compared to those without.Pediatric nurses that worked with adolescents compared to those thatdid not showed higher frequency of burnout in the former group (77%vs. 32%, p=0.0001). Multivariable analysis revealed that adequatequarantine adherence increased the presence of anxiety in 4.6 times[OR4.6(CI 1.1-20.2), p=0.04]. Conclusion: most pediatric nurseswho had worked in the frontline of COVID-19 were under precariousconditions, working with reduced team, and with an expressivechanges in their monthly income. Current anxiety was a relevantissue, burnout was also an important mental condition for theseprofessionals, reinforcing culture of good teamwork, collaborationpractices and psychological/psychiatric approach.Objetivo: avaliar problemas de saúde mental em enfermeiros pediátricosdurante a pandemia causada pelo coronavírus 2019. Método: estudotransversal realizado com enfermeiros pediátricos do Instituto da Criançae do Adolescente, por meio de uma pesquisa online de autoavaliaçãosobre prática clínica e impacto na saúde mental, durante a pandemiade COVID-19. Foram avaliadas escalas de autoavaliação validadaspara ansiedade, depressão e burnout. Resultados: 107/298(36%)enfermeiros responderam, dos quais 90% eram do sexo feminino,a mediana de idade atual era 41(23-64) anos, 68% trabalhavamcom adolescentes, 66% trabalhavam na linha de frente. Burnout,ansiedade e depressão moderada/grave ocorreram em 65%, 72%e 74% dos enfermeiros, respectivamente. Falta de protocolo detratamento padronizado nas enfermarias (27% vs. 10%, p=0,049),depressão moderada/grave (74% vs. 16%, p=0,002) e burnout (82%vs. 58%, p=0,01) foram significativamente maiores em enfermeirospediátricos com ansiedade, em comparação com enfermeiros sem essacondição. Os enfermeiros pediátricos que trabalhavam com adolescentesapresentaram maior frequência de burnout, quando comparados aos quenão trabalhavam com esse grupo (77% vs. 32%, p=0,0001). A análisemultivariada revelou que o cumprimento adequado da quarentenaaumentou a presença de ansiedade em 4,6 vezes [OR 4.6(IC 1,1-20,2),p=0,04]. Conclusão: A maioria dos enfermeiros pediátricos atuavana linha de frente da COVID-19, em condições precárias, trabalhandocom equipe reduzida e enfrentando perdas expressivas de renda. Aansiedade atual foi um tema relevante e o burnout também foi umacondição mental importante para esses profissionais, reforçando acultura do bom trabalho em equipe, das práticas de colaboração e docuidado psicológico/psiquiátrico

Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case

Prospective cohort studies to evaluate the safety and immunogenicity of the 2013, 2014, and 2015 seasonal influenza vaccines produced by Instituto Butantan

ABSTRACT Annual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Forty-seven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA)

Risdiplam in Type 1 Spinal Muscular Atrophy

BackgroundType 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein.MethodsWe report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds.ResultsA total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study.ConclusionsIn infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)The small molecule risdiplam increased the expression of SMN protein in blood in 21 infants with type 1 spinal muscular atrophy. Post hoc clinical features of sitting ability and respiratory status were reported

Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls

Background Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. Methods We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. Results A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P&lt;0.001 for all comparisons). The most common serious adverse events were pneumonia, bronchiolitis, hypotonia, and respiratory failure. Conclusions In this study involving infants with type 1 SMA, risdiplam resulted in higher percentages of infants who met motor milestones and who showed improvements in motor function than the percentages observed in historical cohorts. Longer and larger trials are required to determine the long-term safety and efficacy of risdiplam in infants with type 1 SMA. (Funded by F. Hoffmann-La Roche; FIREFISH ClinicalTrials.gov number, .)Small-Molecule SMN2 Modifier in Type 1 SMA The pre-mRNA SMN2 splicing modifier risdiplam was administered orally to 41 infants with type 1 spinal muscular atrophy. After 12 months of treatment, 12 infants were able to sit without support, and most had better scores on motor-performance scales than the upper limit of confidence intervals from historical controls