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1.
Lancet ; 384(9960): 2123-31, 2014 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-25145775

RESUMO

BACKGROUND: Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. METHODS: In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. FINDINGS: Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. INTERPRETATION: Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. FUNDING: Novartis Vaccines.


Assuntos
Portador Sadio/prevenção & controle , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Neisseria meningitidis Sorogrupo B , Neisseria meningitidis , Adolescente , Feminino , Humanos , Masculino , Método Simples-Cego , Adulto Jovem
2.
J Pediatr Gastroenterol Nutr ; 52(5): 595-600, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21464752

RESUMO

OBJECTIVE: The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. PATIENTS AND METHODS: : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN. RESULTS: Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. CONCLUSIONS: The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.


Assuntos
Enterocolite Necrosante/cirurgia , Intestino Delgado/cirurgia , Jejunostomia/efeitos adversos , Hepatopatias/etiologia , Nutrição Parenteral/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Bilirrubina/sangue , Enterocolite Necrosante/complicações , Feminino , Idade Gestacional , Humanos , Incidência , Lactente , Enteropatias/etiologia , Enteropatias/terapia , Hepatopatias/sangue , Hepatopatias/epidemiologia , Modelos Logísticos , Masculino , Razão de Chances , Complicações Pós-Operatórias/sangue , Fatores de Risco , Fatores Sexuais
3.
J Pediatr ; 157(2): 203-208.e1, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20447649

RESUMO

OBJECTIVE: To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN: Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS: Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION: The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.


Assuntos
Enterocolite Necrosante/complicações , Enterocolite Necrosante/diagnóstico , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/diagnóstico , Peso ao Nascer , Estudos de Coortes , Enterocolite Necrosante/cirurgia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Análise Multivariada , Razão de Chances , Pediatria/métodos , Gravidez , Estudos Prospectivos , Fatores de Risco , Síndrome do Intestino Curto/cirurgia
4.
Pediatr Blood Cancer ; 52(2): 259-62, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18937333

RESUMO

BACKGROUND: We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm(3) within the first 12 weeks. These patients were followed for the next year. METHODS: Platelet counts were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. RESULTS: Eight of the 11 initial responders maintained a platelet count over 150,000/mm(3) without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm(3) without the need for further intervention. CONCLUSIONS: Rituximab resulted in sustained efficacy with platelet counts of 50,000/mm(3) or higher in 11 of 36 patients (31%).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Murinos , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Hemorragia , Humanos , Lactente , Masculino , Contagem de Plaquetas , Recidiva , Indução de Remissão , Rituximab
5.
Vaccine ; 35(3): 427-434, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-27912986

RESUMO

BACKGROUND: University students have high rates of pharyngeal carriage of Neisseria meningitidis. Interruption of carriage acquisition is an important mechanism of vaccines for inducing herd protection. 4CMenB and MenACWY-CRM vaccines have been shown to be immunogenic against meningococcal serogroups B and ACWY respectively in younger age groups, and also to elicit a modest impact on meningococcal carriage in vaccinated students. However, vaccine responses in university students and the impact of serum bactericidal antibody (SBA) titers on meningococcal carriage are undetermined. METHODS: Immunogenicity of two 4CMenB doses or one MenACWY-CRM dose was measured in university students at Months 2, 4, 6 and 12 post-first vaccination. Immunogenicity of one MenACWY-CRM dose in students with previous meningococcal serogroup C conjugate vaccination was also assessed. Immune responses were measured with an SBA assay using human complement (hSBA) against three reference strains for serogroup B and against one strain for each for serogroups C and Y. Correlations between hSBA titers and meningococcal carriage were analyzed. RESULTS: All subjects demonstrated robust functional antibody responses to both vaccines at Month 2 and a high proportion maintained protective hSBA titers up to Month 12. At baseline, carriage of disease-associated serogroup B strains and serogroups C and Y were higher in subjects with already-protective hSBA titers. Post-vaccination, while both 4CMenB and MenACWY-CRM elicited robust immunogenicity in students, significant correlations between post-vaccination hSBA titers and carriage of disease-associated serogroups were not observed. CONCLUSIONS: 4CMenB and MenACWY-CRM were both highly immunogenic. There was no correlation between carriage and post-vaccination hSBA titers.


Assuntos
Portador Sadio/prevenção & controle , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Nasofaringe/microbiologia , Neisseria meningitidis/isolamento & purificação , Adolescente , Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Portador Sadio/microbiologia , Feminino , Humanos , Masculino , Infecções Meningocócicas/microbiologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/classificação , Método Simples-Cego , Estudantes , Universidades , Adulto Jovem
6.
Blood ; 107(7): 2639-42, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16352811

RESUMO

We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50,000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.


Assuntos
Anticorpos Monoclonais/toxicidade , Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/toxicidade , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Murinos , Criança , Pré-Escolar , Humanos , Hipotensão/induzido quimicamente , Seleção de Pacientes , Estudos Prospectivos , Rituximab , Doença do Soro/induzido quimicamente , Resultado do Tratamento
7.
Infect Immun ; 70(6): 2796-804, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12010965

RESUMO

The possibility of concomitant immunity and its potential mechanisms in Onchocerca volvulus infection were examined by analyzing cytokine and antibody responses to infective larval (third-stage larvae [L3] and molting L3 [mL3]), adult female worm (F-OvAg), and skin microfilaria (Smf) antigens in infected individuals in a region of hyperendemicity in Cameroon as a function of age. Peripheral blood mononuclear cell interleukin 5 (IL-5) responses to F-OvAg and Smf declined significantly with age (equivalent to years of exposure to O. volvulus). In contrast, IL-5 secretion in response to L3 and mL3 remained elevated with increasing age. Gamma interferon responses to L3, mL3, and F-OvAg were low or suppressed and unrelated to age, except for responses to Smf in older subjects. IL-10 levels were uniformly elevated, regardless of age, in response to L3, mL3, and F-OvAg but not to Smf, for which levels declined with age. A total of 49 to 60% of subjects had granulocyte-macrophage colony-stimulating factor responses to all O. volvulus antigens unrelated to age. Analysis of levels of stage-specific immunoglobulin G3 (IgG3) and IgE revealed a striking, age-dependent dissociation between antibody responses to larval antigens (L3 and a recombinant L3-specific protein, O. volvulus ALT-1) which were significantly increased or maintained with age and antibody responses to F-OvAg, which decreased. Levels of IgG1 to L3 and F-OvAg were elevated regardless of age, and levels of IgG4 increased significantly with age, although not to O. volvulus ALT-1, which may have unique L3-specific epitopes. Immunofluorescence staining of whole larvae showed that total anti-L3 immunoglobulin levels also increased with the age of the serum donor. The separate and distinct cytokine and antibody responses to adult and infective larval stages of O. volvulus which are age related are consistent with the acquisition of concomitant immunity in infected individuals.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-5/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Adolescente , Adulto , Fatores Etários , Animais , Anticorpos Anti-Helmínticos/sangue , Divisão Celular , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Larva , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/parasitologia , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/parasitologia , Masculino , Pessoa de Meia-Idade , Oncocercose/sangue , Oncocercose/parasitologia , Pele/parasitologia
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