RESUMO
BACKGROUND: The long-term effect of nutritional intervention with hydrolysate infant formulas on allergic manifestations in high-risk children is uncertain. OBJECTIVE: We sought to investigate the effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age. METHODS: We analyzed data from participants of the prospective German Infant Nutritional Intervention study after 10 years of follow-up. At birth, children were randomly assigned to receive, for the first 4 months, one of 4 blinded formulas as breast milk substitute, if necessary: partially hydrolyzed whey formula (pHF-W), extensively hydrolyzed whey formula (eHF-W), extensively hydrolyzed casein formula (eHF-C), or standard cow's milk formula. Outcomes were parent-reported, physician-diagnosed allergic diseases. Log-binomial regression models were used for statistical analysis. RESULTS: The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was 0.87 (95% CI, 0.77-0.99) for pHF-W, 0.94 (95% CI, 0.83-1.07) for eHF-W, and 0.83 (95% CI, 0.72-0.95) for eHF-C compared with standard cow's milk formula. The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis (n = 988) effects were stronger. The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis. CONCLUSION: The significant preventive effect on the cumulative incidence of allergic diseases, particularly AD, with pHF-W and eHF-C persisted until 10 years without rebound, whereas eHF-W showed no significant risk reduction. There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age.
Assuntos
Intervenção Médica Precoce , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Proteínas do Leite/imunologia , Animais , Bovinos , Criança , Pré-Escolar , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Proteínas do Leite/administração & dosagem , Avaliação de Resultados em Cuidados de Saúde , PrevalênciaRESUMO
OBJECTIVE: The German Infant Nutritional Intervention (GINI) trial, a prospective, randomized, double-blind intervention, enrolled children with a hereditary risk for atopy. When fed with certain hydrolyzed formulas for the first 4 months of life, the risk was reduced by 26-45% in PP and 8-29% in intention-to-treat (ITT) analyses compared with children fed with regular cow's milk at age 6. The objective was to assess the cost-effectiveness of feeding hydrolyzed formulas. PATIENTS AND METHODS: Cost-effectiveness was assessed with a decision tree model programmed in TreeAge. Costs and effects over a 6-yr period were analyzed from the perspective of the German statutory health insurance (SHI) and a societal perspective at a 3% effective discount rate followed by sensitivity analyses. RESULTS: The extensively hydrolyzed casein formula would be the most cost-saving strategy with savings of 478 per child treated in the ITT analysis (CI95%: 12 ; 852 ) and 979 in the PP analysis (95%CI: 355 ; 1455 ) from a societal perspective. If prevented cases are considered, the partially whey hydrolyzed formula is cost-saving (ITT -5404 , PP -6358 ). From an SHI perspective, the partially whey hydrolyzed formula is cost-effective, but may also be cost-saving depending on the scenario. An extensively hydrolyzed whey formula also included into the analysis was dominated in all analyses. CONCLUSIONS: For the prevention of AE, two formulas can be cost-effective or even cost-saving. We recommend that SHI should reimburse formula feeding or at least the difference between costs for cow's milk formula and the most cost-effective formula.
Assuntos
Dermatite Atópica/prevenção & controle , Fórmulas Infantis/economia , Hidrolisados de Proteína/economia , Absenteísmo , Animais , Caseínas/economia , Caseínas/uso terapêutico , Criança , Pré-Escolar , Dermatite Atópica/dietoterapia , Dermatite Atópica/economia , Método Duplo-Cego , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Leite/efeitos adversos , Proteínas do Leite/economia , Proteínas do Leite/uso terapêutico , Prevalência , Hidrolisados de Proteína/uso terapêutico , Risco , Proteínas do Soro do LeiteRESUMO
BACKGROUND: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. OBJECTIVE: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial. METHODS: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. RESULTS: In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. CONCLUSION: The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.
Assuntos
Hipersensibilidade/prevenção & controle , Fórmulas Infantis , Caseínas , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipersensibilidade/epidemiologia , Lactente , Recém-Nascido , Masculino , Proteínas do Leite , Prevalência , Hidrolisados de Proteína , Inquéritos e Questionários , Proteínas do Soro do LeiteRESUMO
OBJECTIVE: In 2002, the Medical Licensing Board prescribed fundamental changes in medical education. The reformed curriculum set its focus on bed-side teaching in small groups, problem-based courses, and training of communication skills. The previous curriculum did not include the teaching of communication skills to future physicians. Physicians thus felt unprepared for the doctor-patient communication. METHOD: Within the newly derived Medical Curriculum Munich (MeCuMLMU), the School of Medicine at the Ludwig-Maximilian-University of Munich implemented in 2005 a teaching unit named "Breaking Bad News" in order to train the students' communication skills. Its main elements are videotaped role-plays and the subsequent video-based analyses. In the role-plays, students experience the parts of a physician and a couple of parents. The task of the physician is to break the news of a severe condition to the parents of a child. The teaching units are held by members of the department of child psychiatry together with fifteen members of the department of paediatrics who had been instructed in analyzing videotaped role-plays. A manual was developed to facilitate a standardized approach. RESULTS AND CONCLUSIONS: The teaching units were evaluated by means of questionnaires filled in by students and tutors. The evaluation showed that "Breaking Bad News" was highly appreciated by both students and tutors. Our experience showed that this type of instruction is suitable to improve the communication skills of medical students, and it is feasible despite the relatively extensive technical and personnel resources needed.
Assuntos
Psiquiatria do Adolescente/educação , Psiquiatria Infantil/educação , Estágio Clínico , Comunicação , Aprendizagem Baseada em Problemas , Relações Profissional-Família , Gravação em Vídeo , Adolescente , Criança , Retroalimentação , Alemanha , Humanos , Pais/psicologia , Desempenho de PapéisRESUMO
BACKGROUND: Cystic fibrosis (CF) is characterized by chronic bacterial broncho-pulmonary infection. Although intravenous (i.v.) antibiotic therapy is regarded as standard treatment in CF, only few randomised trials comparing different antibiotic compounds exist. METHODS: We report on a prospective multicenter interventional trial of i.v. meropenem (120 mg/kg/day) or i.v. ceftazidime (200-400 mg/kg/day), each administered together with i.v. tobramycin (9-12 mg/kg/day). Outcome measures were changes in lung function, microbiological sputum burden and blood inflammatory marker. Liver and renal function values were measured to assess safety. RESULTS: One hundred eighteen patients (59/59) were included into the study with the following indications: first infection of P. aeruginosa (n=6), acute pulmonary exacerbation (n=34) and suppression therapy of chronic P. aeruginosa colonization (n=78). Both treatments improved lung function measures, bacterial sputum burden and CRP levels with no differences between treatment groups observed. A significant higher elevation for alkaline phosphatase (p<0.0001) was observed for patients in the meropenem/tobramycin group. CONCLUSIONS: i.v. antibiotic therapy in CF patients with meropenem/tobramycin is as effective as with ceftazidime/tobramycin regarding lung function, microbiological sputum burden and systemic inflammatory status. Hepato-biliary function should be monitored carefully during i.v. treatment, possibly important in CF patients with pre-existing liver disease.
Assuntos
Antibacterianos/administração & dosagem , Ceftazidima/administração & dosagem , Fibrose Cística/tratamento farmacológico , Tienamicinas/administração & dosagem , Tobramicina/administração & dosagem , Adolescente , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Fibrose Cística/sangue , Fibrose Cística/complicações , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Meropeném , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the association between the introduction of solid foods in the first 12 months and the occurrence of eczema during the first 4 years of life in a prospective study of newborns. STUDY DESIGN: Data were taken from annually administered questionnaires from a large birth cohort (recruited 1995-1998) comprised of an intervention and a nonintervention group. Outcomes were doctor-diagnosed and symptomatic eczema. Multiple generalized estimation equation models were performed for the 2 study groups. RESULTS: From the 5991 recruited infants, 4753 (79%) were followed up. The 2 study groups were different in their family risk of allergies and feeding practices. No association was found between the time of introduction of solids or the diversity of solids and eczema. In the nonintervention group, a decreased risk was observed for avoidance of soybean/nuts, but an increased risk was seen in doctor-diagnosed eczema for the avoidance of egg in the first year. CONCLUSION: The evidence from this study supports neither a delayed introduction of solids beyond the fourth month nor a delayed introduction of the most potentially allergenic solids beyond the sixth month of life for the prevention of eczema. However, effects under more extreme conditions cannot be ruled out.
Assuntos
Dermatite Atópica/prevenção & controle , Dieta , Alimentos Infantis , Dermatite Atópica/epidemiologia , Eczema/epidemiologia , Eczema/prevenção & controle , Saúde da Família , Feminino , Hipersensibilidade Alimentar/prevenção & controle , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
INTRODUCTION: Gastroesophageal reflux has been suggested as an underlying cause of chronic lung disease. The aim of this study was to assess the value of pepsin and bile acids, both components of GI secretions, in the lungs of children with chronic lung diseases as possible markers for gastroesophageal reflux disease and their relation to oxidation and inflammation. MATERIALS AND METHODS: BAL was performed in 96 children with different chronic lung diseases. Gastroesophageal reflux was analyzed by two-channel, 24-h esophageal pH measurements. Lung pepsin and bile acids were measured in BAL enzymatically, interleukin (IL)-8 by enzyme-linked immunosorbent assay, and protein carbonyls by slot blot immunoassay. RESULTS: Sixty-five of the 96 children (68%) had an extensive proximal acidic reflux index. Children with reflux had higher pepsin concentrations in their BAL fluid (BALF), compared to children without reflux despite low specificity. No differences were observed for bile acids. Percentages of neutrophils, levels of protein carbonyls, and levels of IL-8 in BALF correlated with the number of proximal reflux events. CONCLUSIONS: Pulmonary microaspiration as demonstrated by pepsin detection in BALF is common in children with chronic lung diseases, suggesting that gastroesophageal reflux may contribute significantly to the disease pathogenesis. BALF pepsin concentration correlates positively with the number of proximal reflux events. Protein oxidation in BALF is higher in children with extensive proximal acidic reflux, suggesting that pulmonary microaspirations contribute to lung damage.
Assuntos
Ácidos e Sais Biliares/metabolismo , Líquido da Lavagem Broncoalveolar/química , Refluxo Gastroesofágico/metabolismo , Pneumopatias/metabolismo , Pepsina A/metabolismo , Biomarcadores/metabolismo , Lavagem Broncoalveolar , Criança , Pré-Escolar , Doença Crônica , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Concentração de Íons de Hidrogênio , Inflamação/metabolismo , Pneumopatias/etiologia , Masculino , Oxirredução , Estudos Retrospectivos , Fatores de Risco , Estatísticas não ParamétricasAssuntos
Dieta , Proteínas do Leite , Leite , Animais , Aleitamento Materno , Feminino , Humanos , Imunoglobulina E/metabolismo , Lactente , Recém-Nascido , Masculino , Leite/efeitos adversos , Proteínas do Leite/imunologia , PartoAssuntos
Antiasmáticos , COVID-19 , Administração por Inalação , Antiasmáticos/uso terapêutico , HumanosAssuntos
Transtorno do Deficit de Atenção com Hiperatividade , Doenças Autoimunes , Criança , Família , Feminino , Humanos , Gravidez , GestantesAssuntos
Influenza Humana , Gestantes , Família , Feminino , Humanos , Influenza Humana/prevenção & controle , Gravidez , VacinaçãoRESUMO
Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis.
Assuntos
Antineoplásicos/efeitos adversos , Hidratação/métodos , Nutrição Parenteral/métodos , Estomatite/terapia , Adolescente , Composição Corporal , Água Corporal , Criança , Pré-Escolar , Feminino , Humanos , Infecções/etiologia , Masculino , Estudos Prospectivos , Estomatite/induzido quimicamenteRESUMO
In this study, we investigated galacturonic (GalAc)- and mannuronic (ManAc) acids as novel targeting ligands for receptor-mediated gene delivery. GalAc and ManAc were coupled to either polyethyleneimine (PEI) or PEI-polyethyleneglycol (PEG). Furthermore, lactobionic acid (LacAc), which comprises a GalAc-related carbohydrate ring, was coupled to each of the polymers through its open-chain gluconic acid moiety. The molar mass distributions of the polymers were characterized by analytical ultracentrifugation and size exclusion chromatography. PEI-conjugate-pDNA complexes were transfected into HepG2-, HeLa-, and 16HBE14o(-)-cells. Gene expression mediated by GalAc- and LacAc-functionalized PEI-conjugates was lower than for PEI. In contrast, gene expression mediated by ManAc-functionalized PEI-conjugates was up to three orders of magnitude higher than for the other tested PEI-conjugates, in particular for negatively charged gene vectors at low N/P ratios, independent of the cell line. Pre-incubation of cells with an excess of ManAc before transfection significantly inhibited transfection rates only for ManAc-functionalized PEI-conjugates. Coupling of methyl-alpha-d-mannuronic acid to PEI resulted in significantly lower transfection rates than for ManAc-PEI based complexes. Together with fluorescence microscopy images of fluorescein-labelled ManAc-functionalized dextrans and FACS analyses of cells, these results demonstrate that receptor-mediated endocytosis of ManAc-PEI-conjugate-pDNA complexes via ManAc-specific receptors was involved in gene transfer. In conclusion, ManAc-modification of PEI-polymers represents a novel strategy for receptor-mediated gene delivery which could be promising for in vivo application.