Linguistic validation of cystic fibrosis quality of life questionnaires

OBJECTIVE: The purpose of this study was to validate the Portuguese translations of four cystic fibrosis quality of life questionnaires (CFQ). The first three were developed for patients with cystic fibrosis aged from 6 to 11 years, from 12 to 13 years and 14 years or more, while the fourth was developed for the parents of patients aged 6 to 13 years. MATERIAL AND METHODS: The four CFQ translations contained from 35 to 50 questions covering nine domains and were validated as follows: translation from English to Portuguese, pilot application, back translation and then approval by the author of the English versions. The four translations were applied to 90 stable patients (30 from each age group) and the parents of patients aged 6-13 years (n = 60), on two occasions with a 13 to 17 day interval. Intraclass Correlation Coefficients (ICC) were used to measure reproducibility. This study was approved by the Commission for Ethics in Research at the institution. RESULTS:Reproducibility was good (ICC = 0.62 to 0.99) for the four translations in all domains, with the exceptions of the Digestion domain for the 6 to 11 and 12 to 13 years age groups with ICC = 0.59 and 0.47, respectively and the Social Role domain for the 14 and over age group (ICC = -0.19 ) CONCLUSION: The translation and cultural adaptation for Brazil resulted in four CFQ versions that are easy to understand and offer good reproducibility.OBJETIVO: O propósito deste estudo foi validar em português as quatro versões de questionários de qualidade de vida em fibrose cística, desenvolvidos para pacientes com fibrose cística de 6 a 11 anos, de 12 a 13 e mais de 14 anos, e para os pais de pacientes de 6 a 13 anos. MATERIAL E MÉTODOS: A validação das quatro versões de questionários de qualidade de vida em fibrose cística (de 35 e 50 questões, abrangendo nove domínios) constou de: versão inglês-português, aplicação-piloto, tradução retrógrada e aprovação da autora da versão inglesa. As quatro versões foram aplicadas a 90 pacientes estáveis (30 de cada grupo etário) e aos pais de doentes de 6-13 anos (n = 60), em duas entrevistas, com intervalo de 13-17 dias. Foi avaliada a reprodutibilidade pelo coeficiente de correlação intraclasse (CCI). O estudo foi aprovado pela comissão de ética em pesquisa da instituição. RESULTADOS: A reprodutibilidade foi boa (CCI = 0,62 a 0,99) para as quatro versões, em todos os domínios, exceto o digestivo (CCI = 0,59 e CCI = 0,47) para os grupos etários de 6 a 11 e 12 a 13 anos, respectivamente, e domínio papel social (CCI = -0,19 ) para o grupo acima de 14 anos. CONCLUSÃO: A tradução e a adaptação à língua e à cultura brasileiras das quatro versões de questionários de qualidade de vida em fibrose cística mostraram-se de fácil entendimento e boa reprodutibilidade.Universidade de São Paulo Faculdade de Medicina Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFaculdade de Medicina do ABCUNIFESP-EPM Centro de Reabilitação PulmonarUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversity of Miami Department of PsychologyUNIFESP, EPM, Centro de Reabilitação PulmonarSciEL

Bronchopulmonary dysplasia

OBJECTIVE: To present a wide-ranging review of the literature on bronchopulmonary dysplasia, covering new definitions, pathophysiology, prevention, treatment, prognosis and progression. SOURCES OF DATA: The most relevant articles published on the subject since it was first described in 1967 were selected from MEDLINE search results. SUMMARY OF THE FINDINGS: Bronchopulmonary dysplasia is considered one of the primary causes of chronic lung disease among infants. It is associated with frequent and prolonged hospital admissions, in particular for pulmonary diseases, with high rates of mortality and alterations to neuropsychomotor development and pondero-statural growth. Pathogenesis is complex, being primarily influenced by prematurity, infection, supplementary oxygen and mechanical ventilation. Prevention involves appropriate prenatal care, the prevention of premature delivery, prenatal corticosteroids, surfactant replacement therapy and protective ventilatory strategies. Treatment of bronchopulmonary dysplasia patients demands a multidisciplinary team. When indicated, oxygen supplementation is extremely important. Despite increased risk of morbidity and mortality during the first years of life, long term progress is favorable in the majority of cases. CONCLUSIONS: Bronchopulmonary dysplasia has been and continues to be studied in great depth with the objective of identifying its causes and possible prevention and treatment strategies. Controversies remain with respect of these issues and also about the prognosis of these patients, in particular when the subject is long-term progress of new bronchopulmonary dysplasia patients.OBJETIVO: Apresentar uma ampla revisão da literatura sobre displasia broncopulmonar, abordando novas definições, fisiopatologia, prevenção, tratamento, prognóstico e evolução. FONTE DOS DADOS: Foram selecionados os artigos mais relevantes sobre o tema, desde a sua descrição inicial, em 1967, pesquisados na MEDLINE. SÍNTESE DOS DADOS: A displasia broncopulmonar é considerada uma das principais causas de doença pulmonar crônica em lactentes. Está associada a hospitalizações freqüentes e prolongadas, especialmente por doenças pulmonares, altos índices de mortalidade e alterações no desenvolvimento neuropsicomotor e no crescimento pôndero-estatural. A patogênese é complexa e influenciada principalmente por prematuridade, infecção, oxigênio suplementar e ventilação mecânica. A prevenção envolve o acompanhamento pré-natal adequado, a prevenção do parto prematuro, o uso pré-natal do corticosteróide, a terapia de reposição de surfactante e o uso de estratégias ventilatórias protetoras. O tratamento do paciente com displasia broncopulmonar demanda uma equipe multidisciplinar. Quando indicada, a suplementação de oxigênio é de extrema importância. Apesar de maior risco de morbimortalidade nos primeiros anos de vida, a evolução em longo prazo é favorável na maioria das vezes. CONCLUSÕES: A displasia broncopulmonar vem sendo profundamente estudada na tentativa de identificação das suas causas e possibilidades de prevenção e de tratamento. Ainda existem controvérsias quanto a esses assuntos e também em relação ao prognóstico desses pacientes, especialmente quando se trata da evolução tardia da nova displasia broncopulmonar.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaHospital e Maternidade Santa Joana Unidade de Terapia Intensiva NeonatalUniversidade de São Paulo Faculdade de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL

O impacto de primeiro ano de tratamento com dornase alfa nos parâmetros clínicos de pacientes com fibrose cística: estudo multicêntrico brasileiro

OBJECTIVE:To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients.METHODS:The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated.RESULTS:Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases.CONCLUSIONS:The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the intervention.OBJETIVO:Relatar el impacto clínico del primer año de tratamiento con dornasa alfa conforme a la franja de edad, en una cohorte de pacientes brasileños con fibrosis quística (FC).MÉTODOS:El presente estudio analizó datos de 152 pacientes elegibles, de 16 centros de referencia para FC, los que contestaron a los cuestionarios clínicos y realizaron pruebas laboratoriales, al inicio del tratamiento con la dornasa alfa (T0) y después de 6 (T2) y 12 (T4) meses de la intervención. Se analizaron 3 grupos etarios: 6-11, 12-13 e >14 años de edad. Se evaluaron las pruebas pulmonares, la microbiología de vías aéreas, las atenciones de emergencia, hospitalizaciones y tratamientos emergenciales y de rutina. Las estadísticas descriptivas, pruebas t y chi-cuadrado y ANOVA fueron usadas cuando pertinentes.RESULTADOS:El tratamiento regular se basó en la fisioterapia respiratoria, ejercicios regulares, encimas pancreáticas, vitaminas, broncodilatadores, corticosteroides y antibióticos. En los 6 meses anteriores al estudio (fase T0), las hospitalizaciones por exacerbación pulmonar ocurrieron en 38, 10 y 61,4%, respectivamente, para las tres franjas de edad analizadas. En el grupo 6-11 años, hubo reducción significativa de atenciones de emergencia después de 1 año de tratamiento. No hubo modificaciones significativas de volumen espiratorio forzado en el 1er segundo (VEF1), capacidad vital forzada (CVF), saturación de oxígeno (SpO)2 e índice de Tiffeneau, en todos grupos. El escore de Schwachman-Kulczychi mejoró significativamente en el grupo de más edad. Los últimos 6 meses de tratamiento, la colonización crónica o intermitente por P. aeruginosa fue detectada en el 75, 71,4 y 62,5%, respectivamente, mientras que por S. aureus ocurrió en 68,6, 66,6 y 41,9% de los casos en cada grupo de edad.CONCLUSIONES:La intervención con dornasa alfa resultó en mantenimiento de los parámetros pulmonares y fue asociada a la reducción significativa de visitas a la emergencia por exacerbación pulmonar en el grupo de 6 a 11 años de edad, con mejora del escore clínico en el grupo >14 años de edad, al final de un año de estudio.OBJETIVO:Relatar o impacto clínico do primeiro ano de tratamento com dornase alfa de acordo com a faixa etária, numa coorte de pacientes brasileiros com fibrose cística (FC).MÉTODOS:O presente estudo analisou dados de 152 pacientes elegíveis, de 16 centros de referência para FC, os quais responderam aos questionários clínicos e realizaram testes laboratoriais, ao início do tratamento com dornase alfa (T0) e após seis (T2) e 12 (T4) meses da intervenção. Analisaram-se três grupos etários: seis a 11, 12 a 13 e >14 anos de idade. Avaliaram-se os testes pulmonares, a microbiologia de vias aéreas, os atendimentos de emergência, as hospitalizações e os tratamentos emergenciais e rotineiros. O teste t de Student, o qui-quadrado e a análise de variância foram usados quando pertinentes.RESULTADOS:O tratamento baseou-se em fisioterapia respiratória, exercícios regulares, enzimas pancreáticas, vitaminas, broncodilatadores, corticosteroides e antibióticos. Nos seis meses anteriores ao estudo (fase T0), as hospitalizações por exacerbação pulmonar ocorreram em 38,0, 10,0 e 61,4%, respectivamente para as três faixas etárias analisadas. No grupo de seis a 11 anos, houve redução significativa de atendimentos de emergência após um ano de tratamento. Não houve modificações significativas de volume expiratório forçado no primeiro segundo (VEF1), capacidade vital forçada (CVF), saturação de oxigênio (SpO)2 e índice de Tiffeneau em todos os grupos. O escore de Shwachman-Kulczychi melhorou significativamente no grupo de mais idade. Nos últimos seis meses de tratamento, a colonização crônica ou intermitente por P.aeruginosa foi detectada em 75,0, 71,4 e 62,5%, respectivamente, enquanto a colonização por S.aureus ocorreu em 68,6, 66,6 e 41,9% dos casos em cada grupo etário.CONCLUSÕES:A intervenção com dornase alfa resultou em manutenção dos parâmetros pulmonares e associou-se à redução significativa de visitas à emergência por exacerbação pulmonar no grupo de seis a 11 anos de idade, com melhora do escore clínico no grupo >14 anos de idade ao final de um ano de estudo.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)Universidade Federal do Rio Grande do Sul Faculdade de MedicinaSecretaria da Saúde da Bahia Hospital Especializado Octávio MangabeiraUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasHospital de Base do Distrito FederalUNIFESP, EPMSciEL

Effects of Pilates mat exercises on muscle strength and on pulmonary function in patients with cystic fibrosis

Objective: To analyze the effects of Pilates mat exercises in patients with cystic fibrosis (CF). Methods: This was a clinical trial involving 19 CF patients recruited from either the CF Outpatient Clinic of the State University at Campinas Hospital de Clinicas or the Children's Institute of the University of So Paulo School of Medicine Hospital das Clinicas. All of the patients performed Pilates mat exercises for four months (one 60-min session per week). the variables studied (before and after the intervention) were respiratory muscle strength, MIP, MEP, FVC, and FEV1. Results: After the intervention, MIP was significantly higher in the male patients (p = 0.017), as were MIP and MEP in the female patients (p = 0.005 and p = 0.007, respectively). There were no significant differences between the pre- and post-intervention values of FVC or FEV1, neither in the sample as a whole nor among the patients of either gender. Conclusions: Our results show that Pilates mat exercises have beneficial effects on respiratory muscle strength in CF patients.Univ Estadual Campinas, Campinas, SP, BrazilUniv Estadual Campinas, Programa Posgrad Saude Crianca & Adolescente, Campinas, SP, BrazilUniv Estadual Campinas, Dept Pediat, Fac Ciencias Med, Campinas, SP, BrazilUniv São Paulo, Fac Med, Inst Crianca, Unidade Pneumol Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Programa Posgrad Reabilitacao, São Paulo, BrazilUniversidade Federal de São Paulo, Programa Posgrad Reabilitacao, São Paulo, BrazilWeb of Scienc

Fibrose cística com dosagem de cloro no suor normal: relato de caso

A fibrose cística é uma doença genética usualmente diagnosticada através de teste anormal de dosagem de cloro no suor. Os autores descrevem o caso de uma paciente de 18 anos com bronquiectasias e infecção crônica por P. aeruginosa mas com dosagens de cloro no suor normais que evoluiu com rápido declínio da função pulmonar e piora clínica, a despeito do tratamento. Dada a forte suspeita de fibrose cística, realizou-se um teste de genotipagem amplo, evidenciando a presença de mutações deltaF508 e 3849+10kb C->;T, deste modo confirmando o diagnóstico de fibrose cística . Apesar da dosagem de cloro no suor ainda ser considerada o padrão ouro para o diagnóstico de fibrose cística , testes diagnósticos alternativos como genotipagem e medidas eletrofisiológicas devem ser empregados se há suspeita de fibrose cística , mesmo com níveis normais ou limítrofes de níveis de cloro no suor.Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->;T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels

Temporal Logic for Programmable Logic Controllers

We address the formal verification of the control software of critical systems, i.e., ensuring the absence of design errors in a system with respect to requirements. Control systems are usually based on industrial controllers, also known as Programmable Logic Controllers (PLCs). A specific feature of a PLC is a scan cycle: 1) the inputs are read, 2) the PLC states change, and 3) the outputs are written. Therefore, in order to formally verify PLC, e.g., by model checking, it is necessary to describe the transition system taking into account this specificity and reason both in terms of state transitions within a cycle and in terms of larger state transitions according to the scan-cyclic semantics. We propose a formal PLC model as a hyperprocess transition system and temporal cycle-LTL logic based on LTL logic for formulating PLC property. A feature of the cycle-LTL logic is the possibility of viewing the scan cycle in two ways: as the effect of the environment (in particular, the control object) on the control system and as the effect of the control system on the environment. For both cases we introduce modified LTL temporal operators. We also define special modified LTL temporal operators to specify inside properties of scan cycles. We describe the translation of formulas of cycle-LTL into formulas of LTL, and prove its correctness. This implies the possibility ofmodel checking requirements expressed in logic cycle-LTL, by using well-known model checking tools with LTL as specification logic, e.g., Spin. We give the illustrative examples of requirements expressed in the cycle-LTL logic

Темпоральная логика для программируемых логических контроллеров

We address the formal verification of the control software of critical systems, i.e., ensuring the absence of design errors in a system with respect to requirements. Control systems are usually based on industrial controllers, also known as Programmable Logic Controllers (PLCs). A specific feature of a PLC is a scan cycle: 1) the inputs are read, 2) the PLC states change, and 3) the outputs are written. Therefore, in order to formally verify PLC, e.g., by model checking, it is necessary to describe the transition system taking into account this specificity and reason both in terms of state transitions within a cycle and in terms of larger state transitions according to the scan-cyclic semantics. We propose a formal PLC model as a hyperprocess transition system and temporal cycle-LTL logic based on LTL logic for formulating PLC property. A feature of the cycle-LTL logic is the possibility of viewing the scan cycle in two ways: as the effect of the environment (in particular, the control object) on the control system and as the effect of the control system on the environment. For both cases we introduce modified LTL temporal operators. We also define special modified LTL temporal operators to specify inside properties of scan cycles. We describe the translation of formulas of cycle-LTL into formulas of LTL, and prove its correctness. This implies the possibility ofmodel checking requirements expressed in logic cycle-LTL, by using well-known model checking tools with LTL as specification logic, e.g., Spin. We give the illustrative examples of requirements expressed in the cycle-LTL logic.Мы исследуем формальную верификацию управляющего программного обеспечения критических систем, т. е. проверку соответствия функционирования проектируемой системы предъявленным требованиям. Важнейший класс управляющего программного обеспечения составляют программы для программируемых логических контроллеров (ПЛК). Особенностью программ ПЛК является цикл управления: 1) считываются входы, 2) изменяются состояния ПЛК и 3) записываются выходы. Поэтому для формальной верификации программ ПЛК нужна возможность описывать учитывающие эту специфику системы переходов, а также определять свойства систем, моделирующих программы ПЛК, как относительно переходов внутри цикла, так и относительно более крупных переходов в соответствии с семантикой цикла управления. Мы предлагаем формальную модель программы ПЛК как систему переходов гиперпроцессов и темпоральную логику cycle-LTL для формализации свойств ПЛК. Особенностью логики cycle-LTL является возможность рассматривать свойства систем управления двояким образом: воздействие окружения на систему управления и воздействие системы управления на окружение. Мы определяем модификации стандартных темпоральных операторов логики LTL для каждого из этих случаев, а также для свойств внутри цикла управления. Рассмотрены примеры требований, определенных в нашей логике. Описана трансляция формул cycle-LTL в формулы LTL и показана её корректность. Доказана возможность сведения задачи верификации методом проверки моделей для требований, определенных в логике cycle-LTL, к задаче верификации требований, определенных в стандартной логике LTL

The recombinant fusion protein CFP10–ESAT6–dIFN has protective effect against tuberculosis in guinea pigs

Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10–ESAT6–dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response. Double intradermal immunization of guinea pigs with the tested fusion protein (2 × 0.5 µg) induces a protective effect against subsequent Mtb infection. The immunized guinea pigs do not develop the symptoms of acute TB and their body weight gain was five times more as compared with the non-immunized infected guinea pigs. The animal group immunized with this dose of antigen displays the minimum morphological changes in the internal organs and insignificant inflammatory lesions in the liver tissue, which complies with a decrease in the bacterial load in the spleen and average Mtb counts in macrophages