Reducing public health costs with infant formulas: oral food challenge and misdiagnosed or outgrown cow's milk protein allergy

Background: Accurate diagnosis and appropriate management of cow's milk protein allergy (CMPA) are crucial for avoiding unnecessary prescription of infant formulas. Here, we aimed to use the oral food challenge (OFC) for CMPA confirmation and for assessing development of natural tolerance to milk, in children with clinical CMPA diagnosis. We also assessed the economic impact in public health-care costs of reducing the prescription of infant formulas (provided by the São Paulo State's public health service, in Brazil, until two years of age) after ruling out CMPA diagnosis in children with negative OFC results. Methods: We reviewed medical records of 76 children [41 males, median age = 2.0 years (0.8-5.0)] who underwent OFC from January 2016 to June 2018, 30 of whom were ≤2 years old. Results: Before OFC, 52 (68.4%), 20 (26.3%) and five (5.3%) children were diagnosed with non-IgE-mediated, IgE-mediated and mixed CMPA, respectively. Most children were fed with aminoacid-based formulas (n=29, 38%). OFC was negative in 58 (76%) children, thus ruling out CMPA diagnosis. Out of 18 (24%) OFC-positive children, most (n=10, 56%) had gastrointestinal symptoms. After ruling out CMPA diagnosis, a mean of 152.3 formula cans (2,161.14 US dollars) were saved per children by the public health service. The total amount saved was 64,834.27 US dollars. Conclusions: OFC proved important not only for ruling out misdiagnosed CMPA, but also for preventing the indiscriminate use of infant formulas, which, in turn, had positive consequences for public health costs.

Objetivos: O diagnóstico preciso e o manejo apropriado da alergia à proteína do leite de vaca (alergia ao leite, AL) são cruciais para evitar a prescrição desnecessária de fórmulas infantis. Aqui, tivemos o objetivo de usar o teste de provocação oral aberto (TPOA) para a confirmação do diagnóstico de AL e para avaliar o desenvolvimento de tolerância natural ao leite, em crianças com diagnóstico clínico de AL. Também avaliamos o impacto nos custos de saúde pública da redução da prescrição de fórmulas infantis (fornecidas pelo serviço de saúde do estado de São Paulo até os dois anos de idade) após descartar o diagnóstico de AL em crianças com TPOA negativo. Métodos: Revisamos prontuários de 76 crianças [41 do sexo masculino, mediana de idade = 2. anos (0,8-5,0)] submetidas ao TPOA de janeiro de 2016 a junho de 2018, 30 das quais tinham dois anos de idade ou menos. Resultados: Antes do TPOA, 52 (68.4%), 20 (26.3%) e cinco (5.3%) crianças foram diagnosticadas com AL não mediada por IgE, mediada por IgE e de mecanismo misto, respectivamente.  A maioria das crianças era alimentada com fórmulas baseadas em aminoácidos (n=29, 38%). O TPOA foi negativo em 58 (76%) crianças, descartando, assim, o diagnóstico de AL. De 18 (24%) crianças positivas para o TPOA, a maioria (n=10, 56%) tinha sintomas gastrointestinais. Após descartar o diagnóstico de AL, uma média de 152,3 latas de fórmula (R$ 8.644,57) foram economizadas, por criança, pelo serviço público de saúde. O montante total economizado foi de R$ 259.337,09. Conclusão: O TPOA se mostrou importante, não apenas para descartar o diagnóstico de AL, como também para evitar o uso indiscriminado de fórmulas infantis, o que, por sua vez, teve consequências positivas para os custos de saúde pública.

Preservation of cytotoxic granule production in response to mycobacterial antigens by T-lymphocytes from vertically HIV-infected Brazilian youth on effective combined antiretroviral therapy

ABSTRACT Background: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. Methods: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. Results: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. Conclusions: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.

Improving patient care trajectories: an innovative quasi-experimental research method for health services.

Scores to predict treatment outcomes have earned a well-deserved place in healthcare practice. However, when used to help achieve excellence in the care of a given disease, scores should also take into account organizational and social aspects. This article aims to create scores to obtain key variables and its application in the management of care of a given disease. We present a method called Epidemiological Planning for Patient Care Trajectory (PELC) and its application in a research of HIV pediatric patients. This case study is presented by means of two studies. The first study deals with the development of the method PELC. The second is HIV Pediatric case-control study based on PELC method. HIV pediatric research - the first practical PELC application - found these four key variables to the individual quality level care trajectories: adherence to ART, attending at least one appointment with the otolaryngologist, attending at least one appointment with social services, and having missed one or more routine appointments. We believe PELC method can be used in researches about any kind of care trajectories, contributing to quality level advancements in health services, with emphasis on patient safety and equity in healthcare.

Improving patient care trajectories: an innovative quasi-experimental research method for health services / Melhoria da linha de cuidado do paciente: um método de pesquisa quase-experimental inovador para serviços de saúde

Abstract Scores to predict treatment outcomes have earned a well-deserved place in healthcare practice. However, when used to help achieve excellence in the care of a given disease, scores should also take into account organizational and social aspects. This article aims to create scores to obtain key variables and its application in the management of care of a given disease. We present a method called Epidemiological Planning for Patient Care Trajectory (PELC) and its application in a research of HIV pediatric patients. This case study is presented by means of two studies. The first study deals with the development of the method PELC. The second is HIV Pediatric case-control study based on PELC method. HIV pediatric research - the first practical PELC application - found these four key variables to the individual quality level care trajectories: adherence to ART, attending at least one appointment with the otolaryngologist, attending at least one appointment with social services, and having missed one or more routine appointments. We believe PELC method can be used in researches about any kind of care trajectories, contributing to quality level advancements in health services, with emphasis on patient safety and equity in healthcare.

Resumo O uso de escores preditores ganhou merecido espaço nas práticas de saúde. Todavia, quando usados para alcançar a excelência do cuidado, os escores devem levar em conta também aspectos organizacionais e sociais. O objetivo deste artigo é criar escores para obter variáveis-chaves e sua aplicação na gestão do cuidado de uma determinada doença. Apresentamos um método chamado Planejamento Epidemiológico de Linha de Cuidado (PELC) e sua aplicação em pesquisa com pacientes HIV pediátricos. Este estudo de caso é apresentado por meio de dois estudos. O primeiro, sobre o desenvolvimento do método PELC. O segundo é um estudo de caso-controle em pacientes pediátricos com HIV, realizado com base no método PELC. A pesquisa HIV Pediátrico - primeira aplicação do método PELC - encontrou 4 variáveis chaves para o grau de qualidade da trajetoria de cuidado do paciente: aderência ao antirretroviral; ter pelo menos uma consulta no otorrinolaringologista; ter pelo menos uma consulta com assistente social; e ter faltado uma ou mais vezes a consulta de rotina. Acreditamos que o PELC pode ser aplicado em qualquer tipo de linha de cuidado, contribuindo para avanços na qualidade dos serviços de saúde, com ênfase na segurança do paciente e na equidade.

Endocarditis by Kocuria rosea in an immunocompetent child.

Kocuria rosea belongs to genus Kocuria (Micrococcaceae family, suborder Micrococcineae, order Actinomycetales) that includes about 11 species of bacteria. Usually, Kocuria sp are commensal organisms that colonize oropharynx, skin and mucous membrane; Kocuria sp infections have been described in the last decade commonly affecting immunocompromised patients, using intravenous catheter or peritoneal dialysis. These patients had mainly bacteremia/recurrent sepsis. We hereby describe the case of a 10-year-old girl, immunocompetent, who had endocarditis/sepsis by K. rosea which was identified in five different blood cultures by Vitek 2 ID-GPC card (BioMérieux, France). Negative HIV serology, blood count within normal range of leukocytes/neutrophils and lymphocytes, normal fractions of the complement, normal level of immunoglobulins for the age; lymphocyte immunophenotyping was also within the expected values. Thymus image was normal at chest MRI. No catheters were required. Identification of K. rosea was essential to this case, allowing the differentiation of coagulase-negative staphylococci and use of an effective antibiotic treatment. Careful laboratory analysis of Gram-positive blood-born infections may reveal more cases of Kocuria sp infections in immunocompetent patients, which may collaborate for a better understanding, prevention and early treatment of these infections in pediatrics.

Usefulness of pharmacy dispensing records in the evaluation of adherence to antiretroviral therapy in Brazilian children and adolescents.

INTRODUCTION: Adherence, which is crucial to the success of antiretroviral therapy (HAART), is currently a major challenge in the care of children and adolescents living with HIV/AIDS. OBJECTIVE: To evaluate the prevalence of nonadherence to HAART using complementary instruments in a cohort of children and adolescents with HIV/AIDS followed in a reference service in Campinas, Brazil. METHODS: The level of adherence of 108 patients and caregivers was evaluated by an adapted standardized questionnaire and pharmacy dispensing records (PDR). Non-adherence was defined as a drug intake lower than 95% (on 24-hour or seven-day questionnaires), or as an interval of 38 days or more for pharmacy refills. The association between adherence and clinical, immunological, virological, and psychosocial characteristics was assessed by multivariate analysis. RESULTS: Non-adherence prevalence varied from 11.1% (non-adherent in three instruments), 15.8% (24-hour self-report), 27.8% (seven-day self-report), 45.4% (PDR), and 56.3% (at least one of the outcomes). 24-hour and seven-day self-reports, when compared to PDR, showed low sensitivity (29% and 43%, respectively) but high specificity (95% and 85%, respectively). In multivariate analysis, medication intolerance, difficulty of administration by caregiver, HAART intake by the patient, lower socioeconomical class, lack of virological control, missed appointments in the past six months, and lack of religious practice by caregiver were significantly associated with non-adherence. CONCLUSION: A high prevalence of HAART non-adherence was observed in the study population, and PDR was the most sensitive of the tested instruments. The instruments employed were complementary in the identification of non-adherence.

Usefulness of pharmacy dispensing records in the evaluation of adherence to antiretroviral therapy in Brazilian children and adolescents

INTRODUCTION: Adherence, which is crucial to the success of antiretroviral therapy (HAART), is currently a major challenge in the care of children and adolescents living with HIV/AIDS. OBJECTIVE: To evaluate the prevalence of nonadherence to HAART using complementary instruments in a cohort of children and adolescents with HIV/AIDS followed in a reference service in Campinas, Brazil. METHODS: The level of adherence of 108 patients and caregivers was evaluated by an adapted standardized questionnaire and pharmacy dispensing records (PDR). Non-adherence was defined as a drug intake lower than 95% (on 24-hour or seven-day questionnaires), or as an interval of 38 days or more for pharmacy refills. The association between adherence and clinical, immunological, virological, and psychosocial characteristics was assessed by multivariate analysis. RESULTS: Non-adherence prevalence varied from 11.1% (non-adherent in three instruments), 15.8% (24-hour self-report), 27.8% (seven-day self-report), 45.4% (PDR), and 56.3% (at least one of the outcomes). 24-hour and seven-day self-reports, when compared to PDR, showed low sensitivity (29% and 43%, respectively) but high specificity (95% and 85%, respectively). In multivariate analysis, medication intolerance, difficulty of administration by caregiver, HAART intake by the patient, lower socioeconomical class, lack of virological control, missed appointments in the past six months, and lack of religious practice by caregiver were significantly associated with non-adherence. CONCLUSION: A high prevalence of HAART non-adherence was observed in the study population, and PDR was the most sensitive of the tested instruments. The instruments employed were complementary in the identification of non-adherence.

Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus.

OBJECTIVES: To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. METHODS: A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. RESULTS: A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. CONCLUSIONS: HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.

Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus / Qualidade do sono e qualidade de vida em adolescentes infectados pelo vírus da imunodeficiência humana

OBJECTIVES: To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. METHODS: A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. RESULTS: A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. CONCLUSIONS: HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.

OBJETIVOS: Avaliar as características do sono de adolescentes infectados pelo HIV e estudar se os aspectos psicossociais estão associados à qualidade do sono. MÉTODOS: Estudo transversal, que avaliou 102 adolescentes, com idades entre 10 e 20 anos, infectados pelo HIV, e 120 controles, de ambos os gêneros. Para a coleta de dados, aplicaram-se: a Sleep Disturbance Scale for Children, a Epworth Sleepiness Scale, e o Pediatric Quality of Life Inventory. RESULTADOS: Verificou-se prevalência de distúrbios do sono em 77,4% dos pacientes e em 75% nos controles, e houve correlação entre qualidade do sono e de vida. Adolescentes HIV-positivos apresentaram maior pontuação nos distúrbios respiratórios do sono e maior prevalência de sonolência diurna excessiva. CONCLUSÕES: Adolescentes infectados pelo HIV apresentaram qualidade de sono semelhante à da população saudável. Isso provavelmente decorre pela melhora de suas condições de vida resultante do sucesso da terapia antirretroviral em pacientes HIV-positivos e pelas vulnerabilidades que afetam adolescentes brasileiros de grandes centros urbanos.

Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing.

CONTEXT AND OBJECTIVE: Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. DESIGN AND SETTING: Retrospective study at Universidade Estadual de Campinas. METHODS: Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. RESULTS: A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3) teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7), or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22% and 21% of the total calls. CONCLUSION: Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing / Experiência inicial de um hospital universitário utilizando a telemedicina na promoção de educação através de vídeo-conferências

CONTEXT AND OBJECTIVE: Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. DESIGN AND SETTING: Retrospective study at Universidade Estadual de Campinas. METHODS: Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. RESULTS: A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3) teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7), or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22 percent and 21 percent of the total calls. CONCLUSION: Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

CONTEXTO E OBJETIVO: Serviços de telessaúde e telemedicina estão avançando rapidamente, com um espectro cada vez maior de tecnologias da informação e comunicação que podem ser aplicadas de forma ampla para a saúde da população, bem como para a educação médica. O objetivo deste artigo é relatar a experiência da nossa instituição com 100 reuniões por videoconferência entre cinco diferentes países das Américas no período de um ano. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo na Universidade Estadual de Campinas. MÉTODOS: Através de um banco de dados do Microsoft Excel, foram analisadas retrospectivamente todas as conferências realizadas em nossa instituição, de setembro de 2009 a agosto de 2010, em todas as especialidades. RESULTADOS: Um total de 647 alunos, médicos e professores participaram das reuniões de telemedicina. Em média, 8,3 (± 4,3) teleconferências foram realizadas mensalmente durante o período analisado. Excluindo os feriados e o mês de inauguração do anfiteatro de telemedicina, as nossas taxas de teleconferência atingiram a média de 10,3 (± 2,7), ou duas teleconferências sobre uma média semanal. Cirurgia do Trauma e reuniões sobre segurança dos pacientes foram, de longe, os temas mais comuns discutidos em nossas reuniões de teleconferência, correspondendo por 22 por cento e 21 por cento do total de chamadas. CONCLUSÃO: Nossa experiência com as reuniões de telemedicina aumentou o interesse dos alunos, ajudou a nossa instituição a acompanhar e discutir protocolos que já são aceitos em todo o mundo e estimulou nossos professores a promover pesquisas relacionadas à telemedicina em suas próprias especialidades, mantendo-os atualizados. Essas reuniões com envolvimento de alta tecnologia encurtaram as distâncias dentro de nosso país vasto e com outros centros de referência no exterior. Esta proximidade virtual permitiu discussões com alunos e residentes sobre estágios internacionais a fim de aumentar seu conhecimento global e melhorar a sua educação dentro da própria instituição.

Vírus respiratórios e ventilação mecânica em lactentes brasileiros / Respiratory virus and mechanical ventilation in Brazilian infants

Introdução: Entre lactentes, Vírus Sincicial Respiratório e Metapneumovírus são agentes importantes de infecção respiratória baixa com necessidade de ventilação mecânica. Índice de Ventilação e Relação PaO2/FiO2 podem ser fatores prognósticos do tempo de ventilação mecânica nestes casos. Métodos: Dentre 284 lactentes (zero a 12 meses), hospitalizados por infecção respiratória aguda baixa em 2004, 2007 e 2008, foram avaliados 20 que necessitaram de ventilação mecânica. Análise da secreção nas ofaríngea para vírus por Polimerase Chain Reaction foi realizada; o Índice de Ventilação Mecânica e a Relação PaO2/FiO2 foram obtidos nos primeiros cinco dias de ventilação mecânica; tempo prolongado de ventilação pulmonar mecânica foi considerado sete dias ou mais. Resultados: Dez em vinte lactentes foram identificados com Vírus Sincial Respiratório; 0/20 foram positivos para Metapneumovírus. A análise estatística comparativa não mostrou diferenças entre Índice de Ventilação Mecânica e Relação PaO2/FiO2 e tempo de ventilação pulmonar prolongada entre os grupos Vírus Sincicial Respiratório positivo e negativo. A identificação do genótipo foi realizada em 6 de 10 Vírus Sincicial Respiratórios encontrados; o pequeno número de casos não permitiu relacionar a apresentação clínica com as características virais (subgrupos e genótipos). Conclusão: Índice de Ventilação Mecânica e Relação PaO2/FiO2 não foram úteis como fatores prognósticos de tempo de ventilação mecânica prolongada para este grupo. De maneira ideal, estudo com maior número de lactentes, teste para vários vírus, e testes para a imunidade inata e adaptativa, poderia mostrar o impacto destes fatores na evolução dos lactentes em ventilação pulmonar mecânica. Infelizmente, recursos para pesquisas como esta não estão facilmente disponíveis.

Background: Among infants, respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are important agents of lower respiratory tract infection requiring mechanical ventilation. Ventilation index and PaO2/FiO2 ratio may be prognostic factors for duration of mechanical ventilation in these cases. Methods: From a population of 284 infants (aged zero to 12 months) hospitalized with lower respiratory tract infection in 2004, 2007, and 2008, 20 infants requiring mechanical ventilation were evaluated. Nasopharyngeal secretions were analyzed for virus detection using a polymerase chain reaction (PCR) test. Ventilation index and PaO2/FiO2 ratio were obtained during the first five days of mechanical ventilation. Prolonged mechanical ventilation was defined as required ventilatory support for 7 days or longer. Results: Out of 20 infants assessed, 10 were positive for RSV and none for HMPV. Comparative statistical analysis showed no difference in ventilation index, PaO2/FiO2 ratio, and prolonged mechanical ventilation between RSV-positive and –negative groups. Genotypic identification was performed in 6 of 10 RSV-positive infants. The small number of cases did not allow a statistical correlation between clinical presentation and viral characteristics (subgroups and genotypes). Conclusion: Ventilation index and PaO2/FiO2 were not useful as prognostic factors for prolonged mechanical ventilation in this group. Ideally, studies involving more infants and including tests for several viruses and for innate and adaptive immunity should be conducted to further evaluate the impact of these factors on the outcome of infants requiring mechanical ventilation. Unfortunately, resources for this type of research are not readily available.

O papel do hormônio de crescimento no tratamento dos distúrbios endócrino-metabólicos do paciente com a síndrome da imunodeficiência adquirida (Aids): [revisão] / The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (Aids) patients: [review]

As primeiras descrições da síndrome da imunodeficiência adquirida (Aids) associavam-se à síndrome de emaciamento, e os distúrbios metabólicos às alterações na composição corporal. Após a introdução da terapia anti-retroviral altamente ativa (HAART), houve declínio na desnutrição, e surge a lipodistrofia como importante distúrbio metabólico. A Aids também se caracteriza por distúrbios hormonais, principalmente no eixo hormônio de crescimento/fator de crescimento insulina-like tipo 1 (GH/IGF-1). O uso do GH recombinante humano (hrGH) foi inicialmente indicado na síndrome de emaciamento, a fim de aumentar a massa muscular. Embora também não existam dúvidas quanto aos efeitos do hrGH na lipodistrofia, a diminuição na sensibilidade à insulina limita o seu uso, o qual ainda não está oficialmente aprovado. A diversidade nos esquemas de tratamento é outro limitante do uso dessa medicação em pacientes com Aids. Esta revisão apresenta os principais distúrbios endócrino-metabólicos associados à Aids e ao uso do hrGH nessas condições.

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6 percent male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 percent (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95 percent confidence interval (CI), 1.50-8.70; aOR, 3.58; 95 percent CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95 percent CI, 1.60-53.08; aOR, 9.05; 95 percent CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

CONTEXTO E OBJETIVO: Reações adversas a drogas são um problema significativo em pacientes sob terapia antiretroviral (TARV). Determinamos a freqüência de valores elevados de enzimas hepáticas em um grupo de crianças e adolescentes infectados pelo HIV sob TARV e os fatores de risco associados. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado na Divisão de Imunodeficiência em Pediatria, Hospital das Clínicas, Universidade Estadual de Campinas. MÉTODOS: Foram analisados prontuários médicos de 152 crianças e adolescentes (54,6 por cento masculino) infectados pelo HIV sob TARV, com dosagens de enzimas hepáticas, em média, 2,6 exames por paciente. A mediana de idade foi 7,48 anos. Clinicamente os pacientes foram classificados nas categorias N (6), A (29), B (78) e C (39). Foram avaliados os níveis séricos de aspartato aminotransferase e alanina aminotransferase. O sistema de escore da hepatotoxicidade foi: grau 1 (1,1 a 4,9 x• limite superior ao normal, i.e., LSN), grau 2 (5,0 - 9,9 x LSN), grau 3 (10,0 - 15,0 x •LSN) e grau 4 (>15,0 x •LSN). Para determinar os fatores de risco de hepatotoxicidade, foram avaliados odds ratio (OR) e odds ratio ajustado (aOR) para idade, gênero, contagem de linfócitos TCD4+ e uso de medicações. RESULTADOS: Observamos hepatotoxicidade grau 1 em 19,7 por cento (30/152) pacientes. Não foi detectada hepatotoxicidade grau 2, 3 ou 4. Houve uma associação significativa entre a hepatotoxicidade e uso de sulfas (OR, 3,61; IC 95 por cento, 1,50 -8,70; ORajustado, 3,58; IC 95 por cento, 1,44 - 8,85) e agentes antituberculose (OR, 9,23; IC 95 por cento, 1,60 - 53,08; ORajustado, 9,05, IC 95 por cento, 1,48 - 55,25), mas não estava associada com TARV. CONCLUSÃO: Um quinto dos pacientes apresentaram hepatotoxicidade leve, atribuída ao uso de agentes antituberculose e sulfas. Nossos resultados sugerem que TARV foi bem tolerada.

Respiratory syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks

Respiratory syncytial virus (RSV) is one of the main causes of acute lower respiratory tract infections worldwide. We examined the incidence and associated risks for RSV infection in infants hospitalized in two university hospitals in the state of São Paulo. We made a prospective cohort study involving 152 infants hospitalized for acute lower respiratory tract infections (ALRTI) in two university hospitals in Campinas, São Paulo, Brazil, between April and September 2004. Clinical and epidemiological data were obtained at admission. RSV was detected by direct immunofluorescence of nasopharyngeal secretions. Factors associated with RSV infection were assessed by calculating the relative risk (RR). The incidence of RSV infection was 17.5 percent. Risk factors associated with infection were: gestational age less than 35 weeks (RR: 4.17; 95 percent confidence interval (CI) 2.21-7.87); birth weight less than or equal to 2,500 grams (RR: 2.69; 95 percent CI 1.34-5.37); mother's educational level less than five years of schooling (RR: 2.28; 95 percent CI 1.13-4.59) and pulse oximetry at admission to hospital lower than 90 percent (RR: 2.19; 95 percent CI 1.10-4.37). Low birth weight and prematurity are factors associated with respiratory disease due to RSV in infants. Low educational level of the mother and poor socioeconomic conditions also constitute risk factors. Hypoxemia in RSV infections at admission indicates potential severity and a need for early oxygen therapy.

Fatores prognósticos para ventilação mecânica em lactentes com doença respiratória aguda baixa / Prognostic factors for mechanical ventilation in infants with acute lower respiratory disease

OBJETIVO: Infecções respiratórias agudas são a causa mais comum de internação hospitalar em pediatria. Uma proporção de pacientes internados necessita de ventilação pulmonar mecânica invasiva (VPMI). Este estudo objetivou avaliar fatores prognósticos para VPMI em lactentes hospitalizados por infecção respiratória aguda baixa. MÉTODOS: Estudo de coorte prospectivo, realizado de abril a setembro de 2004, em dois hospitais universitários da região de Campinas, São Paulo, Brasil. Foram avaliados 152 lactentes internados, registrando-se dados epidemiológicos e clínicos na internação e no seguimento. Analisaram-se dois grupos, de acordo com a necessidade de VPMI, comparando-se os fatores prognósticos. A associação entre fatores de risco e desfecho estudado foi analisada por risco relativo (RR) e intervalos de confiança (IC 95 por cento). RESULTADOS: Vinte e um pacientes (13,81 por cento) necessitaram de VPMI. Fatores significativamente associados à VPMI na admissão foram: idade < 3 meses (RR=2,35, IC 95 por cento:1,06-5,22), aleitamento materno < 1 mês (RR=3,15, IC 95 por cento:1,35-7,35) e cianose (RR=7,55, IC 95 por cento:5,01-11,36). Observou-se risco aumentado no grupo de VPMI para internação > 10 dias (RR=13,69, IC 95 por cento:4,92-38,09), oxigenioterapia > 10 dias (RR=13,57, IC 95 por cento:5,41-34,03), uso de antibióticos (RR=3,03, IC 95 por cento:1,34-6,89) e reinternações (RR=5,23, IC 95 por cento:2,12-12,91). CONCLUSÃO: As associações entre a necessidade de VPMI e baixa idade, tempo curto de aleitamento materno e cianose à admissão demonstram as reduzidas reservas fisiológicas no lactente jovem com infecção respiratória baixa. Caracterizam este grupo de pacientes a necessidade de suporte hospitalar prolongado e intensivo e maior taxa de reinternações.

OBJECTIVE: Acute lower respiratory tract infections are the most common cause of hospital admission in pediatrics. A number of admitted patients need invasive mechanical pulmonary ventilation (IMPV). This study aimed to evaluate prognostic factors for IMPV in infants admitted due to acute lower respiratory infection. METHODS: A prospective cohort study was conducted from April to September, 2004, in two university hospitals of the Campinas metropolitan area, São Paulo, Brazil. One hundred, fifty-two infants were enrolled. Epidemiological and clinical data were recorded at admission and follow-up. Two groups were analyzed, according to the need of IMPV, with a comparison of prognostic factors. Association between risk factors and the outcome were studied and assessed by Relative Risk (RR), with confidence intervals of (95 percentCI). RESULTS: Twenty-one patients (13.81 percent) needed IMPV. Factors significantly associated with IMPV on admission were: age < 3 months (RR=2.35, 95 percentCI:1.06-5.22), breast feeding < 1 month (RR=3.15, 95 percentCI:1.35-7.35) and cyanosis (RR=7.55, 95 percentCI:5.01-11.36). In the IMPV group, increased risks for hospitalization > 10 days (RR=13.69, 95 percentCI:4.92-38.09), oxygen therapy > 10 days (RR=13.57, 95 percentCI:5.41-34.03), antibiotic usage (RR=3.03, 95 percentCI:1.34-6.89) and readmission (RR=5.23, 95 percentCI:2.12-12.91) were observed. CONCLUSION: The associations between need of IMPV and early age, reduced breast feeding and cyanosis demonstrate diminished physiological reserves in the young infant with lower respiratory infection. These patients require prolonged and intensive hospital support and readmission.

Respiratory syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks.

Respiratory syncytial virus (RSV) is one of the main causes of acute lower respiratory tract infections worldwide. We examined the incidence and associated risks for RSV infection in infants hospitalized in two university hospitals in the state of São Paulo. We made a prospective cohort study involving 152 infants hospitalized for acute lower respiratory tract infections (ALRTI) in two university hospitals in Campinas, São Paulo, Brazil, between April and September 2004. Clinical and epidemiological data were obtained at admission. RSV was detected by direct immunofluorescence of nasopharyngeal secretions. Factors associated with RSV infection were assessed by calculating the relative risk (RR). The incidence of RSV infection was 17.5%. Risk factors associated with infection were: gestational age less than 35 weeks (RR: 4.17; 95% confidence interval (CI) 2.21-7.87); birth weight less than or equal to 2,500 grams (RR: 2.69; 95% CI 1.34-5.37); mother's educational level less than five years of schooling (RR: 2.28; 95% CI 1.13-4.59) and pulse oximetry at admission to hospital lower than 90% (RR: 2.19; 95% CI 1.10-4.37). Low birth weight and prematurity are factors associated with respiratory disease due to RSV in infants. Low educational level of the mother and poor socioeconomic conditions also constitute risk factors. Hypoxemia in RSV infections at admission indicates potential severity and a need for early oxygen therapy.

Lack of association between nutritional status and change in clinical category among HIV-infected children in Brazil.

CONTEXT AND OBJECTIVE: Malnutrition is common among HIV-infected children. Our objective was to study the occurrence of malnutrition and its relationship with changes in clinical category among HIV-infected children. DESIGN AND SETTING: Longitudinal study, at the Pediatrics Department and Pediatrics Investigation Center (CIPED), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (Unicamp). METHODS: We reviewed the hospital records of 127 vertically HIV-infected children. Anthropometric measurements were obtained at the beginning of follow-up, at clinical category change and five months later. These were converted to z-scores of weight/age, height/age and weight/height. Data were presented as means, standard deviations, frequency counts and percentages. The Wilcoxon and Kruskal-Wallis tests and odds ratios were used in the analysis. RESULTS: We found that 51 (40.2%) were undernourished and 40 (31.5%) were stunted, with higher risk of being included in clinical category C. There was an association between nutritional condition and the clinical categories of the Centers for Disease Control classification (1994), and with age at symptom onset (except for height z-score). During follow-up, 36 patients (28.4%) changed their clinical category, which occurred early among the undernourished patients. The group that changed its clinical category maintained the same z-score distribution for weight, height and weight/height throughout follow-up. CONCLUSION: Aids manifestation severity was associated with nutritional status and with age at symptom onset, but change in clinical category was not followed by worsening of nutritional status.