CLASSICAL SEROLOGICAL MARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE IN BRAZIL.

BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

Marcadores sorológicos clássicos na doença inflamatória intestinal pediátrica no Brasil / Classical serological markers in pediatric inflammatory bowel disease in brazil

ABSTRACT BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. OBJECTIVE: To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. METHODS: Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. RESULTS: A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). CONCLUSION: In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

RESUMO CONTEXTO: Os anticorpos citoplasmáticos anti-neutrófilos perinuclear (p-ANCA) e anticorpos anti-Saccharomyces cereviciae (ASCAs) são utilizados para diferenciar a doença de Crohn (DC) da colite ulcerativa (CU) e mais recentemente para correlacioná-los com o prognóstico da doença. OBJETIVO: 1) Determinar a acurácia diagnóstica dos marcadores sorológicos na identificação de DC e CU pediátrica em São Paulo, Brasil. 2) Correlacioná-los com as características demográficas e clínicas destas duas doenças. MÉTODOS: Estudo multicêntrico transversal em pacientes com diagnóstico estabelecido de doença inflamatória intestinal (DII) determinando a presença dos marcadores sorológicos ASCAs e p-ANCA, correlacionando seus resultados com os dados demográficos e clínicos, e também em pacientes controles isentos de doenças gastrointestinal. RESULTADOS: 122 pacientes, 74 com DII (46% masculinos) em quatro centros de referência em Gastroenterologia Pediátrica, média de idade 13±7 anos, 49 (66%) com DC e 25 (34%) com CU e 48 controles (54% masculinos). O marcador p-ANCA apresenta maior porcentagem de detecção na CU (69,6%), mas também na DC (30,4%) quando comparado ao grupo controle (P<0,001). Os marcadores ASCA IgA (76,2%) e IgG (94,4%) apresentam maiores porcentagens de detecção na DC, quando comparada ao controle (P<0,001) e que a positividade do marcador esteve relacionada ao uso de medicações em pacientes portadores de DC que realizaram cirurgia (26,86±17,99; P=0,032). CONCLUSÃO: Os resultados dos testes sorológicos em crianças com DII em São Paulo, Brasil, foram altamente específicos, mas pouco sensíveis para auxiliar no diagnóstico, embora com correlação positiva com a gravidade da doença.

The first five-year evaluation of cystic fibrosis neonatal screening program in São Paulo State, Brazil.

The Hospital of the Ribeirão Preto Medical School, University of São Paulo is one of the three screening centers in São Paulo State, Brazil, and has included a test for cystic fibrosis (CF) since February 6, 2010, by a court order. We evaluated the first five years of this CF-newborn screening program. The original immunoreactive trypsinogen (IRT)/IRT screening protocol was adopted in Brazil. A total of 173,571 newborns were screened, 1,922 (1.1%) of whom showed IRT1 ≥ 70ng/mL. Of these, 1,795 (93.4%) collected IRT2, with elevated results (IRT2 ≥ 70ng/mL) in 102 of them (5.2%). We identified a total of 26 CF cases during this period, including three CF cases that were not detected by the CF-newborn screening. The incidence of the disease among the screened babies was 1:6,675 newborns screened. Median age at the initial evaluation was 42 days, comparable to that of neonates screened with the IRT/DNA protocol. Almost all infants with CF already exhibited some manifestations of the disease during the neonatal period. The mutation most frequently detected in the CF cases was F508del. These findings suggest the early age at the beginning of treatment at our center was due to the effort of the persons involved in the program regarding an effective active search. Considering the false negative results of CF-newborn screening and the early onset of clinical manifestations of the disease in this study, pediatricians should be aware of the diagnosis of CF even in children with negative test.

The first five-year evaluation of cystic fibrosis neonatal screening program in São Paulo State, Brazil / Uma avaliação dos primeiros cinco anos do programa de triagem neonatal da fibrose cística no Estado de São Paulo, Brasil / Una evaluación de los primeros cinco años del programa de cribado neonatal de fibrosis cística en el Estado de São Paulo, Brasil

The Hospital of the Ribeirão Preto Medical School, University of São Paulo is one of the three screening centers in São Paulo State, Brazil, and has included a test for cystic fibrosis (CF) since February 6, 2010, by a court order. We evaluated the first five years of this CF-newborn screening program. The original immunoreactive trypsinogen (IRT)/IRT screening protocol was adopted in Brazil. A total of 173,571 newborns were screened, 1,922 (1.1%) of whom showed IRT1 ≥ 70ng/mL. Of these, 1,795 (93.4%) collected IRT2, with elevated results (IRT2 ≥ 70ng/mL) in 102 of them (5.2%). We identified a total of 26 CF cases during this period, including three CF cases that were not detected by the CF-newborn screening. The incidence of the disease among the screened babies was 1:6,675 newborns screened. Median age at the initial evaluation was 42 days, comparable to that of neonates screened with the IRT/DNA protocol. Almost all infants with CF already exhibited some manifestations of the disease during the neonatal period. The mutation most frequently detected in the CF cases was F508del. These findings suggest the early age at the beginning of treatment at our center was due to the effort of the persons involved in the program regarding an effective active search. Considering the false negative results of CF-newborn screening and the early onset of clinical manifestations of the disease in this study, pediatricians should be aware of the diagnosis of CF even in children with negative test.

O Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo é um dos três centros de triagem da fibrose cística (FC) no estado de São Paulo, tendo incluído esse teste desde 6 de fevereiro de 2010, a partir de uma liminar judicial. O estudo avalia os primeiros cinco anos desse programa de triagem neonatal da FC. O Brasil adota o protocolo de triagem original, com o tripsinogênio imunorreativo (IRT)/IRT. Foram triados um total de 173.571 recém-nascidos, dos quais 1.922 (1,1%) mostraram IRT ≥ 70ng/mL. Destes, 1.795 (93,4%) tiveram amostras coletadas para IRT2, com resultados elevados (IRT2 ≥ 70ng/mL) em 102 deles (5,2%). Identificamos um total de 26 casos de FC durante esse período, inclusive 3 casos de FC que não foram detectados com a triagem neonatal. A incidência da FC foi de 1 caso em cada 6.675 recém-nascidos triados. A idade mediana na avaliação inicial foi 42 dias, comparável à idade de recém-nascidos triados com o protocolo IRT/DNA. Quase todos os lactentes com FC já exibiam algumas manifestações da doença durante o período neonatal. A mutação mais comum nos casos de FC foi a F508del. Os resultados em nosso centro indicam que a idade precoce no início do tratamento foi devido aos esforços do programa na implementação de uma busca ativa eficaz. Considerando os resultados falsos-negativos no programa de triagem neonatal para FC e o início precoce das manifestações clínicas da doença neste estudo, os pediatras devem estar cientes da possibilidade de diagnóstico de FC, mesmo em crianças com teste negativo.

El Hospital das Clínicas de la Facultad de Medicina de Ribeirão Preto, São Paulo Universidad es uno de los tres centros de cribado de fibrosis cística (FC) en el estado de São Paulo, incluyendo este test desde el 6 de febrero de 2010, debido a una medida cautelar judicial. El estudio evalúa los primeros cinco años de este programa de cribado neonatal de FC. Brasil adopta el protocolo de cribado original, con el tripsinógeno inmunorreactivo (TIR)/IRT. Se cribaron un total de 173.571 recién nacidos, de los cuales 1.922 (1,1%) mostraron IRT ≥ 70ng/mL. De estos, se obtuvieron 1.795 (93,4%) muestras recogidas para IRT2, con resultados elevados (IRT2 ≥ 70ng/mL) en 102 de ellos (5,2%). Identificamos un total de 26 casos de FC durante ese período, inclusive 3 casos de FC que no fueron detectados con el cribado neonatal. La incidencia de la FC fue de 1 caso por cada 6.675 recién-nacidos cribados. La edad media en la evaluación inicial fue 42 días, comparable a la edad de recién nacidos cribados con el protocolo IRT/DNA. Casi todos los lactantes con FC ya manifestaban algunos síntomas de la enfermedad durante el período neonatal. La mutación más común en los casos de FC era el F508del. Los resultados en nuestro centro indican que la edad precoz en el inicio del tratamiento se debía a los esfuerzos del programa en la implementación de una búsqueda activa eficaz. Considerando los resultados falsos-negativos en el programa de cribado neonatal para FC, y el inicio precoz de las manifestaciones clínicas de la enfermedad en este estudio, los pediatras deben ser conscientes de la posibilidad de diagnóstico de FC, incluso en niños con test negativo.

Acrodermatite enteropática: manifestações clínicas e diagnóstico pediátrico / Acrodermatitis enteropathica: clinical manifestations and pediatric diagnosis

RESUMO Objetivo: Relatar um caso de acrodermatite enteropática, doença rara com herança autossômica recessiva. Relato de caso: Menino de 11 meses de idade apresentava lesões eritematosas simétricas na face, pés, mãos e joelhos, diarreia intermitente, febre e infecções recorrentes desde os seis meses de idade. Ele estava emagrecido e tinha cabelos escassos no couro cabeludo. Foi solicitada a avaliação da concentração sérica de zinco e identificado um nível reduzido de 27,0 mcg/dL (valores de referência: 50,0-120,0). Foi iniciada a suplementação oral com 2,0 mg/kg/dia de sulfato de zinco. Houve melhora rápida e progressiva dos sintomas. Os sintomas reapareceram quando houve uma tentativa de descontinuar a suplementação. Comentários: Reconhecer e tratar adequadamente a acrodermatite enteropática é importante para evitar as complicações da doença.

ABSTRACT Objective: To report a case of acrodermatitis enteropathica, a rare disease with autosomal recessive inheritance. Case description: An 11-month-old boy was presenting symmetrical erythematous and yellowish-brownish crusted lesions on his face, feet, hands and knees, intermittent diarrhea, fever, and recurrent infections since the age of six months. He was thin and had scarce hair on the scalp. The serum zinc level was measured and a reduced level of 27.0 mcg/dL (normal range: 50.0-120.0) was identified. Oral supplementation with 2.0 mg/kg/day of zinc sulfate was immediately initiated. A rapid and progressive improvement of symptoms was observed. The symptoms reappeared with an attempt to stop supplementation. Comments: Recognizing and properly treating acrodermatitis enteropathica is important to prevent complications.

ACRODERMATITIS ENTEROPATHICA: CLINICAL MANIFESTATIONS AND PEDIATRIC DIAGNOSIS. / ACRODERMATITE ENTEROPÁTICA: MANIFESTAÇÕES CLÍNICAS E DIAGNÓSTICO PEDIÁTRICO.

OBJECTIVE: To report a case of acrodermatitis enteropathica, a rare disease with autosomal recessive inheritance. CASE DESCRIPTION: An 11-month-old boy was presenting symmetrical erythematous and yellowish-brownish crusted lesions on his face, feet, hands and knees, intermittent diarrhea, fever, and recurrent infections since the age of six months. He was thin and had scarce hair on the scalp. The serum zinc level was measured and a reduced level of 27.0 mcg/dL (normal range: 50.0-120.0) was identified. Oral supplementation with 2.0 mg/kg/day of zinc sulfate was immediately initiated. A rapid and progressive improvement of symptoms was observed. The symptoms reappeared with an attempt to stop supplementation. COMMENTS: Recognizing and properly treating acrodermatitis enteropathica is important to prevent complications.

OBJETIVO: Relatar um caso de acrodermatite enteropática, doença rara com herança autossômica recessiva. RELATO DE CASO: Menino de 11 meses de idade apresentava lesões eritematosas simétricas na face, pés, mãos e joelhos, diarreia intermitente, febre e infecções recorrentes desde os seis meses de idade. Ele estava emagrecido e tinha cabelos escassos no couro cabeludo. Foi solicitada a avaliação da concentração sérica de zinco e identificado um nível reduzido de 27,0 mcg/dL (valores de referência: 50,0-120,0). Foi iniciada a suplementação oral com 2,0 mg/kg/dia de sulfato de zinco. Houve melhora rápida e progressiva dos sintomas. Os sintomas reapareceram quando houve uma tentativa de descontinuar a suplementação. COMENTÁRIOS: Reconhecer e tratar adequadamente a acrodermatite enteropática é importante para evitar as complicações da doença.

Nutritional status of adolescents with cystic fibrosis treated at a reference center in the southeast region of Brazil.

BACKGROUND: Several factors can interfere with the full physical and emotional growth of adolescents, among them chronic diseases. The aim was to determine the nutritional status of adolescents and to associate it with puberty, pancreatic sufficiency, lung function and age range of Cystic Fibrosis (CF) diagnosis. METHODS: An observational, cross-sectional, retrospective and analytical study was conducted using the data of medical records. SETTING: Reference center in the northeastern region of the state of São Paulo - Brazil. PATIENTS: All adolescents with CF attended in 2010 were included. Some variables included: pancreatic sufficiency (steatocrit >2 %), pancreatic enzymes replacement (yes/no), pubertal status-Tanner criteria (prepubertal: M1/G1, pubertal: M2/G2 to M4/G4, postpubertal: M5/G5), age at CF diagnosis (<2 and ≥2 years of age), Lung function, measured as a predicted forced expiratory volume in 1 s (FEV1). Main outcome measures Nutritional indicators: body mass index for age (BMI/A) and height for age (H/A) with z-score calculated with Anthro Plus software. Cut-off reference points: ≥ z-score -3 and < z-score -2 (thinness); z-score -2 and ≤ z-score-z +1 (normal weight); >z-score +1 (overweight or obesity), and z-score <-2 (low or very low H/A). The groups were compared by the Kruskal-Wallis test. Level of significance: p<0.05. RESULTS: Thirty adolescents. Median (min;max) age: 14.4 (10.1;19.8) years. BMI/A and H/A z-score, respectively: early diagnosis of CF (-0.8; -1.1) or late diagnosis of CF (-0.5;-0.8); with pancreatic insufficiency (-0.7; -0.8) or without pancreatic insufficiency (-0.8; -0.5) and prepubertal (-0.8; -0.7) pubertal (-0.2; -1.5) or postpubertal (-0.7; -0.5). No significant difference (p>0.05) was observed. Patients with and without pancreatic insufficiency, presented H/A borderline z-score (p=0.05). Association between H/A and FEV1 was borderline (p=0.05). CONCLUSIONS: Adolescents presented adequate nutritional status, although with slightly lower values than those of developed countries. FEV1 lower levels occurred more frequently in adolescents with low H/A.

The ontogeny of saliva secretion in infants and esophagoprotection.

BACKGROUND: Several studies have reported that severe reflux esophagitis is rare in infants despite the well known high occurrence of regurgitation in early infancy. There is evidence of the importance of saliva for the pre-epithelial protection of the esophageal mucosa. RESULTS: A longitudinal study conducted on healthy infants indicated that the stimulated capacity of saliva secretion (saliva output per kg of body weight) was significantly higher during their first year of age compared to older children and adults. In addition, this secretion pattern was also observed in low weight newborns during the first weeks of life and persisted in infants with severe protein-calorie malnutrition (marasmus). CONCLUSION: The greater ability to secrete saliva is an important physiological condition that may protect the infant from acid/pepsin aggression to the esophagus during early stages of development.

Early manifestations of cystic fibrosis in a premature patient with complex meconium ileus at birth / Manifestações precoces da fibrose cística em paciente prematuro com íleo meconial complexo ao nascimento

OBJECTIVE: To report a case of a preterm infant with complex meconium ileus at birth and cystic fibrosis. CASE DESCRIPTION: A male infant was born by vaginal delivery at 33 weeks and 5 days of gestational age with respiratory distress and severe abdominal distension. The exploratory laparotomy in the first day of life identified meconium ileus and secondary peritonitis. Ileal resection and ileostomy were performed, followed by reconstruction of the bowel transit at 20 days of life. At 11 days of life, the first immunoreactive trypsinogen (IRT) was 154 ng/mL (reference value = 70), and oral pancreatic enzymes replacement therapy was started. After 23 days, the second IRT was 172ng/mL (reference value = 70). At 35 days of age he was discharged with referrals to primary care and to a special clinic for CF for the determination of sweat chloride. He was received in the outpatient clinic for neonatal screening for CF at 65 days of life presenting malnutrition and respiratory distress. The sweat chloride test was performed, with a positive result (126mEq/L). COMMENTS: This case illustrates the rapid evolution of CF in a premature patient with complex meconium ileus as the first clinical manifestation.

OBJETIVO: Relatar o caso de um recém-nascido prematuro com íleo meconial complexo e fibrose cística. DESCRIÇÃO DO CASO: Recém-nascido do sexo masculino nasceu de parto vaginal com 33 semanas e cinco dias de idade gestacional e apresentou desconforto respiratório e distensão abdominal grave. Foi submetido à laparotomia exploratória no primeiro dia de vida e identificado íleo meconial com peritonite secundária. Foram feitas ressecção ileal e ileostomia, com reconstrução do trânsito intestinal aos 20 dias de vida. Com 11 dias de idade, a primeira dosagem sérica de tripsina imunorreativa (TIR) foi 154ng/mL (valor de referência = 70) e optou-se pelo início da terapia de reposição oral de enzimas pancreáticas. Após 23 dias, a segunda TIR foi 172ng/mL (valor de referência = 70). Recebeu alta com 35 dias de vida com encaminhamentos à rede básica de saúde e ao serviço de referência para a detecção de fibrose cística. Foi atendido no ambulatório de triagem neonatal para fibrose cística aos 65 dias de vida e apresentava desnutrição e desconforto respiratório. O resultado do teste do cloro no suor foi positivo (126 mEq/L). COMENTÁRIOS: O caso ilustra a rápida evolução da fibrose cística em um paciente prematuro com íleo meconial complexo como primeira manifestação clínica.

The ontogeny ofssaliva secretion in infants and esophagoprotection / A ontogenia da secreção de saliva em lactentes e a proteção pré-epitelial do esôfago

Background Several studies have reported that severe reflux esophagitis is rare in infants despite the well known high occurrence of regurgitation in early infancy. There is evidence of the importance of saliva for the pre-epithelial protection of the esophageal mucosa. Results A longitudinal study conducted on healthy infants indicated that the stimulated capacity of saliva secretion (saliva output per kg of body weight) was significantly higher during their first year of age compared to older children and adults. In addition, this secretion pattern was also observed in low weight newborns during the first weeks of life and persisted in infants with severe protein-calorie malnutrition (marasmus). Conclusion The greater ability to secrete saliva is an important physiological condition that may protect the infant from acid/pepsin aggression to the esophagus during early stages of development. .

Contexto Vários estudos têm indicado que a esofagite de refluxo é rara em lactentes no primeiro ano de vida a despeito da elevada ocorrência de regurgitação nesta fase da vida. Há evidências da importância da saliva para a proteção pré-epitelial da mucosa esofágica. Resultados Um estudo longitudinal conduzido em lactentes saudáveis indicou que a capacidade estimulada da secreção de saliva (volume de saliva/kg de peso) foi significativamente elevada no primeiro ano de vida comparada com crianças com mais idade e adultos jovens. Este padrão também foi observado nas primeiras semanas de vida de recém-nascidos com baixo peso e persistiu em lactentes com desnutrição proteico-calórica grave (marasmo) Conclusão A grande habilidade para secretar saliva é uma importante condição fisiológica que pode proteger o lactente da agressão ácido/péptica do esôfago durante os primeiros estágios do seu desenvolvimento. .

[Early manifestations of cystic fibrosis in a premature patient with complex meconium ileus at birth]. / Manifestações precoces da fibrose cística em paciente prematuro com íleo meconial complexo ao nascimento.

OBJECTIVE: To report a case of a preterm infant with complex meconium ileus at birth and cystic fibrosis. CASE DESCRIPTION: A male infant was born by vaginal delivery at 33 weeks and 5 days of gestational age with respiratory distress and severe abdominal distension. The exploratory laparotomy in the first day of life identified meconium ileus and secondary peritonitis. Ileal resection and ileostomy were performed, followed by reconstruction of the bowel transit at 20 days of life. At 11 days of life, the first immunoreactive trypsinogen (IRT) was 154 ng/mL (reference value=70), and oral pancreatic enzymes replacement therapy was started. After 23 days, the second IRT was 172 ng/mL (reference value=70). At 35 days of age he was discharged with referrals to primary care and to a special clinic for CF for the determination of sweat chloride. He was received in the outpatient clinic for neonatal screening for CF at 65 days of life presenting malnutrition and respiratory distress. The sweat chloride test was performed, with a positive result (126mEq/L). COMMENTS: This case illustrates the rapid evolution of CF in a premature patient with complex Meconium ileus as the first clinical manifestation.

[Newborn screening for galactosemia: a health economics evaluation]. / Avaliação econômica em saúde: triagem neonatal da galactosemia.

This study assesses the efficiency of the galactosemia add-on test in neonatal screening performed on regular Guthrie card blood spots. Based on estimated average incidence of galactosemia (1:19,984 newborns) in São Paulo State, Brazil, the study develops a cost-benefit analysis model, using a B/C ratio and a 9.25% annual interest rate in order to decapitalize the results. Sensitivity analysis is also performed, varying (as a function of the interest or discount rate) from 0 and 20% and according to the 95% confidence interval (1:7,494-1:59,953 newborns). The results show that the savings obtained by improved health of galactosemic patients detected early by add-on neonatal screening is superior to the costs (B/C=1.33), characterizing galactosemia add-on testing in neonatal screening as an efficient policy. The lower the prevailing interest rate in the economy, the more efficient the neonatal screening policy.

Avaliação econômica em saúde: triagem neonatal da galactosemia / Newborn screening for galactosemia: a health economics evaluation

Este trabalho avalia a eficiência da adição do exame da galactosemia junto ao Teste do Pezinho. Baseado na incidência média estimada de galactosemia, de 1:19.984 recém-nascidos, no Estado de São Paulo, Brasil, este estudo desenvolve um modelo de análise de custo-benefício, utilizando a relação benefício/custo (B/C), a taxa de juros de 9,25 por cento ao ano para descapitalização dos resultados obtidos. Também se realiza uma análise de sensibilidade, em função da variação da taxa de juros entre 0 e 20 por cento e do intervalo de 95 por cento de confiança da incidência da galactosemia (1:7.494 a 1:59.953 recém-nascidos). A economia obtida com a melhora da saúde das crianças doentes identificadas precocemente é superior aos custos (B/C = 1,33), caracterizando como eficiente a política de adição do exame neonatal para galactosemia no Teste do Pezinho. Quanto menor a taxa de juros vigente na economia, mais eficiente é a política de triagem neonatal, não considerados os custos sociais intangíveis evitados.

This study assesses the efficiency of the galactosemia add-on test in neonatal screening performed on regular Guthrie card blood spots. Based on estimated average incidence of galactosemia (1:19,984 newborns) in São Paulo State, Brazil, the study develops a cost-benefit analysis model, using a B/C ratio and a 9.25 percent annual interest rate in order to decapitalize the results. Sensitivity analysis is also performed, varying (as a function of the interest or discount rate) from 0 and 20 percent and according to the 95 percent confidence interval (1:7,494-1:59,953 newborns). The results show that the savings obtained by improved health of galactosemic patients detected early by add-on neonatal screening is superior to the costs (B/C=1.33), characterizing galactosemia add-on testing in neonatal screening as an efficient policy. The lower the prevailing interest rate in the economy, the more efficient the neonatal screening policy.

Avaliação clínica, nutricional e espirométrica de pacientes com fibrose cística após implantação de atendimento multidisciplinar / Clinical, nutritional and spirometric evaluation of patients with cystic fibrosis after the implementation of multidisciplinary treatment

OBJETIVO: A fibrose cística (FC) é uma doença hereditária, multissistêmica e crônica, para a qual é importante uma abordagem multidisciplinar. O objetivo deste estudo foi mostrar a evolução de um grupo de pacientes com FC após a implantação desse tipo de atendimento. MÉTODOS: Foram analisados retrospectivamente 19 pacientes (idades entre 6 e 29 anos) em acompanhamento clínico no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, na cidade de Ribeirão Preto (SP). Os pacientes foram divididos em dois grupos: grupo 6-12 (6-12 anos) e grupo 13+ (> 12 anos). Dados referentes a índice de massa corporal (IMC), escore Z, escore de Shwachman (ES), número de exacerbações/ano, colonização crônica por Pseudomonas aeruginosa e medidas espirométricas (CVF, VEF1, VEF1 por cento e FEF25-75 por cento) foram obtidos. Os dados foram coletados em dois momentos (antes e após a implantação de atendimento multidisciplinar) e foram analisados com o teste dos postos sinalizados de Wilcoxon. RESULTADOS: A mediana de idade de início de sintomas foi de 10 meses. No grupo 6-12, houve somente um aumento significativo do IMC e da CVF. As outras medidas espirométricas aumentaram, mas não significativamente. No grupo 13+, não houve diferenças significativas entre os dois momentos, sendo que o ES apresentou uma diminuição com significância limítrofe. Houve diminuição não significativa das medidas espirométricas. Entretanto, o número de pacientes com volumes e fluxos alterados diminuiu nos dois grupos. CONCLUSÕES: Apesar do grupo pequeno, a manutenção dos parâmetros espirométricos pode significar estabilidade clínica e funcional. Os pacientes estudados mantiveram estabilidade clínica, funcional e nutricional durante o período, e a implantação de abordagem multidisciplinar pode ter contribuído nesse sentido.

OBJECTIVE: Cystic fibrosis (CF) is a chronic multisystemic hereditary disease for which a multidisciplinary approach must be taken. The objective of this study was to show the evolution of a group of patients with CF after the implementation of multidisciplinary treatment. METHODS: A retrospective study involving 19 patients (6-29 years of age) under clinical follow-up treatment at the University of São Paulo at Ribeirão Preto School of Medicine Hospital das Clínicas, located in the city of Ribeirão Preto, Brazil. The patients were divided into two groups: 6-12 (6-12 years of age) and 13+ (> 12 years of age). We collected data regarding body mass index (BMI), Z score, Shwachman score (SS), number of exacerbations/year, chronic colonization by Pseudomonas aeruginosa, and spirometric measurements (FVC, FEV1, FEV1 percent, and FEF25-75 percent). Data were collected at two different time points (before and after the implementation of the multidisciplinary treatment) and were analyzed with the Wilcoxon signed rank test. RESULTS: The median age at the onset of symptoms was 10 months. In the 6-12 group, only BMI and FVC increased significantly. Although the other spirometric values increased, the differences were not significant. In the 13+ group, there were no significant differences between the two time points. There was a borderline significant decrease in SS and less than significant decreases in the spirometric measurements. However, the number of patients with alterations in volumes and flows decreased in both groups. CONCLUSIONS: Although our patient sample was small, the lack of changes in the spirometric parameters might reflect clinical and functional stability. In all of the patients evaluated, clinical, functional, and nutritional parameters remained stable throughout the study period. The implementation of a multidisciplinary approach might have contributed to this result.

Clinical, nutritional and spirometric evaluation of patients with cystic fibrosis after the implementation of multidisciplinary treatment.

OBJECTIVE: Cystic fibrosis (CF) is a chronic multisystemic hereditary disease for which a multidisciplinary approach must be taken. The objective of this study was to show the evolution of a group of patients with CF after the implementation of multidisciplinary treatment. METHODS: A retrospective study involving 19 patients (6-29 years of age) under clinical follow-up treatment at the University of São Paulo at Ribeirão Preto School of Medicine Hospital das Clínicas, located in the city of Ribeirão Preto, Brazil. The patients were divided into two groups: 6-12 (6-12 years of age) and 13+ (> 12 years of age). We collected data regarding body mass index (BMI), Z score, Shwachman score (SS), number of exacerbations/year, chronic colonization by Pseudomonas aeruginosa, and spirometric measurements (FVC, FEV1, FEV1%, and FEF25-75%). Data were collected at two different time points (before and after the implementation of the multidisciplinary treatment) and were analyzed with the Wilcoxon signed rank test. RESULTS: The median age at the onset of symptoms was 10 months. In the 6-12 group, only BMI and FVC increased significantly. Although the other spirometric values increased, the differences were not significant. In the 13+ group, there were no significant differences between the two time points. There was a borderline significant decrease in SS and less than significant decreases in the spirometric measurements. However, the number of patients with alterations in volumes and flows decreased in both groups. CONCLUSIONS: Although our patient sample was small, the lack of changes in the spirometric parameters might reflect clinical and functional stability. In all of the patients evaluated, clinical, functional, and nutritional parameters remained stable throughout the study period. The implementation of a multidisciplinary approach might have contributed to this result.

Impairment of bone mass development in children with chronic cholestatic liver disease.

OBJECTIVE: To analyse aspects of mineral metabolism, bone mineral density (BMD), bone remodelling activity and serum IGF-1 levels in children with chronic cholestatic disease (CCLD). PATIENTS AND MEASUREMENTS: A total of 13 children with chronic cholestatic liver disease (CCLD; mean age 7.2 +/- 4.8 years) and 22 control subjects (mean age 7.6 +/- 4.5 years) were studied. Serum osteocalcin, bone alkaline phosphatase (BAP), 25-hydroxyvitamin D, PTH and IGF-1 levels and urinary deoxypyridinoline were determined. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine, total hip and whole body. Lumbar spine areal BMD was converted mathematically to apparent volumetric BMD (aBMD) and corrected for the bone age of the patient. RESULTS: Z-score of lumbar spine BMD was lower in CCLD patients than in controls and the difference was maintained when BMD was expressed as aBMD (control = 0.107 +/- 0.02 vs. CCLD = 0.092 +/- 0.02 g/cm(3), P < 0.05) and after conversion for bone age. All participants showed normal 25-hydroxyvitamin D levels, with no significant differences in serum levels of 25-hydroxyvitamin D and PTH between groups. IGF-1 levels were significantly lower in the CCLD group (control = 19.6 +/- 16.8 vs. CCLD = 6.4 +/- 7.6 nmol/l, P < 0.05) and a positive correlation was observed between whole body BMD and IGF-1 in this group. CONCLUSIONS: These results indicate that CCLD limits bone mass gain in children. A reduction in hepatic IGF-1 production might be responsible, at least in part, for the low bone mass of these patients.

Prevalence and demographic characteristics of celiac disease among blood donors in Ribeirão Preto, State of São Paulo, Brazil.

Celiac disease (CD) is an underdiagnosed disease occurring in different clinical forms. This study aimed to determine the prevalence of CD among blood donors from Ribeirão Preto, Brazil, and to study some demographic characteristics of celiac patients. Blood samples from 3000 blood donors were tested for the presence of tissue transglutaminase antibody and positive samples were tested for endomysial antibody. Donors positive to both tests were referred for clinical evaluation and for a jejunal biopsy. Twenty-four samples were moderately/strongly positive for transglutaminase, with 9 of them being endomysial negative and 15 positive. Of the 13 biopsies obtained from 12 females and 1 male, 1 was classified as Marsh grade IV, 4 as grade III, 2 as grade II, 4 as grade I, and 2 as grade 0. Estimated prevalence was therefore 1:273 (0.33%; 95% CI, 0.127 to 0.539). The 1:273 estimated prevalence of CD detected indicates that the disease is not rare in Brazil. The frequency was higher among females and among individuals of European descent, with a significantly higher frequency for a family history of digestive tract cancer or epilepsy.

Gastroesophageal reflux disease: its importance in ear, nose, and throat practice.

OBJECTIVE: Gastroesophageal reflux disease (GERD) has been implicated in various extra-gastroesophageal diseases, especially in the upper and lower airways (atypical GERD). The objective of the present study was to determine the frequency of gastroesophageal and extra-gastroesophageal symptoms in pediatric patients with GERD and their response to the general treatment. MATERIAL AND METHODS: A retrospective study was conducted on 45 children of both sexes aged 3 months-12 years with GERD diagnosed by clinical examination and 24h single-channel pHmetry. The gastroesophageal and extra-gastroesophageal symptoms, the treatment instituted and the response of the patients to the latter were determined. RESULTS: Five symptomatologic groups were identified: gastroesophageal (51.11%), pulmonary (recurrent pneumonia, 40%, and bronchial asthma, 46.67%), chronic cough (64.44%), rhinologic (chronic nasal obstruction, 68.88%, nasal secretion, 55.55%, and nose itching, 46.66%), and pharyngo-otologic (recurrent acute middle ear infection, 35.56%, and recurrent tonsillitis, 24.44%). The response to treatment (antireflux drugs, antiallergic drugs, and surgical procedures) resulted in cure in 24 patients (53.34%), while 21 continued to be symptomatic. The cure rate was 69.56% for the gastroesophageal group, 100% for the recurrent pneumonia group, 80.95% for the bronchial asthma group, 68.96% for the chronic cough group, 83.87% for the chronic nasal obstruction group, 80% for the nasal secretion group, 85.71% for the nose itching group, 100% for the recurrent acute middle ear infection group, and 90.90% for the recurrent tonsillitis group. Total treatment time was 1.8 times longer for the remission of extra-gastroesophageal symptoms. Exclusive antireflux treatment promoted full remission of the otorhinolaryngologic symptoms in 38.89% of patients (nasal-41.17%, recurrent acute middle ear infection-12.5%, and recurrent tonsillitis-18.18%). CONCLUSION: GERD can cause otorhinolaryngologic symptoms in children and remission of these symptoms can be obtained with antireflux therapy.

Anorectal manometry in children with chronic functional constipation.

BACKGROUND: The anorectal manometry is a very utilized and well recognized examination in children with chronic functional constipation. The major manometric findings in these children are: anal hypotonia, anal hypertonia, paradoxal contraction of the external anal sphincter, decreased ability of internal anal sphincter to relax during rectal distension and alterations in rectal contractility, sensibility and compliance. AIMS: To evaluate the anal basal pressure and the relaxation reflex before and after standard treatment for a better understanding of the physiopathologic mechanisms involved in pediatric chronic functional constipation. METHODS: Anorectal manometry was performed before treatment on 20 children with chronic functional constipation aged 4 to 12 years and the results were compared to those obtained after standard treatment, with a good outcome. RESULTS: There was a reduction in anal basal pressure after treatment, but no differences were detected between the anorectal manometries performed before and after treatment in terms of amplitude and duration of relaxation, residual pressure, latency time, or descent and ascent angle. CONCLUSIONS: We conclude that the anal basal pressure decreased in children recovering from chronic functional constipation, but the standard treatment did not provide all the conditions necessary for the relaxation reflex of constipated children to return to the values described in normal children.