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1.
J Pediatr Gastroenterol Nutr ; 55(5): 534-40, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22684351

RESUMO

OBJECTIVES: Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database. METHODS: Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging. RESULTS: Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 ±â€Š4.4 years in both boys and girls. Average follow-up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio [HR] 2.55, 99% confidence interval [CI] 1.21-5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15-17.04) at time of diagnosis and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25-2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90-9.57) or tacrolimus (HR 3.66, 99% CI 1.60-8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery. CONCLUSION: Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.


Assuntos
Colite Ulcerativa/cirurgia , Hipoalbuminemia/complicações , Imunossupressores/uso terapêutico , Proctocolectomia Restauradora , Albumina Sérica/metabolismo , Redução de Peso , Inibidores de Calcineurina , Criança , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Ciclosporina/uso terapêutico , Família , Feminino , Predisposição Genética para Doença , Humanos , Hipoalbuminemia/sangue , Incidência , Masculino , Medição de Risco , Tacrolimo/uso terapêutico , Fatores de Tempo
2.
J Pediatr Gastroenterol Nutr ; 50(1): 27-31, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19934770

RESUMO

OBJECTIVE: Data suggest an increase in the incidence of pediatric inflammatory bowel disease (IBD). We examined the trend of the incidence of IBD in children. PATIENTS AND METHODS: A retrospective investigation was conducted on a cohort of children diagnosed with IBD between 1991 and 2002 who were registered in the IBD center at Texas Children's Hospital. The diagnosis of IBD was based on clinical, radiological, endoscopic, and histological examinations. RESULTS: There were 272 children eligible for the analysis; 56% diagnosed with Crohn disease (CD), 22% with ulcerative colitis (UC), and 22% with indeterminate colitis. The male-to-female ratio was 1.2:1 in CD, 0.6:1 in UC, and 0.8:1 in indeterminate colitis. From 1991 to 2002, the incidence rate has doubled from 1.1/100,000/year (95% confidence interval [CI] 0.85-1.36) to 2.4/1001,000/year (95% CI 2.10-2.77). This trend was valid for CD but not for UC. Whites had higher incidence rate of IBD than African Americans or Hispanics: 4.15/100,000/year (95% CI 3.48-4.82) versus 1.83/100,000/year (95% CI 1.14-2.51), and 0.61/100,000/year (95% CI 0.33-0.89), respectively. African Americans were predominantly diagnosed with CD. CONCLUSIONS: The results demonstrate the rising incidence of IBD among children with evidence of more CD than UC. Recognition of these results will have important implications for diagnosis and management of IBD in children.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Criança , Pré-Escolar , Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores Sexuais , Texas/epidemiologia , População Branca/estatística & dados numéricos
3.
Am J Gastroenterol ; 104(3): 722-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19209163

RESUMO

OBJECTIVES: Endoscopy is commonly performed in the diagnosis of children with inflammatory bowel disease (IBD). The utility of repeat endoscopy for the management of pediatric IBD has not been subject to investigation. The frequency and determinants of changes in medical management resulting from endoscopy are unknown. METHODS: We conducted a cross-sectional cohort study to assess the frequency and determinants of management change in all children (0-21 years) who underwent endoscopy for the surveillance or evaluation of established IBD between July 2002 and July 2006 at 2 referral centers in the United States. Patients were sampled from the Pediatric Endoscopy Database System Clinical Outcomes Research Initiative and a chart review was performed to identify demographic features (age, gender), blood work (hemoglobin, albumin, erythrocyte sedimentation rate, C-reactive protein), and endoscopy results (endoscopic and histologic). An endoscopic score was used to assess mucosal injury. Subjects were divided into two groups for comparative analysis: (i) patients with management changes based on endoscopic or histologic findings, and (ii) patients without changes. RESULTS: We analyzed 285 endoscopic procedures (137 colonoscopies, 109 esophagogastroduodenoscopy (EGD) with colonoscopy, 25 sigmoidoscopies, 8 EGDs, 6 EGDs with sigmoidoscopy) performed in 230 children (mean age 14.5) with established IBD, including 147 with Crohn's disease, 80 with ulcerative colitis, and 3 with indeterminant colitis. Management changes were documented in 119 (42%) procedures, including 58 (20%) immediately after endoscopy, 52 (18%) after histology review, and 9 (3%) after both. Management changes included new medications in 86 cases, discontinuation of a medication in 3 cases, hospital admission in 11, and surgical consult in 14. No significant differences between groups occurred with regard to age, gender, endoscopy type, or infliximab use. The presence of anemia, hypoalbuminemia, or elevated markers of inflammation (ESR, CRP) did not correlate with management outcome. Management changes after endoscopy were more frequent in patients with Crohn's disease as compared to patients with ulcerative colitis. Patients with mucosal injury were more likely to have a management change than those with mucosal healing (80% vs. 20%; P<0.001). CONCLUSIONS: The overall rate of management change after endoscopic evaluation in children with IBD is approximately 42%. Addition of a new medication is the most common intervention. Blood work and patient symptoms before the procedure did not predict management outcome; however, mucosal healing may be an important end point. Our findings suggest that endoscopy is valuable for the evaluation of children with IBD.


Assuntos
Endoscopia Gastrointestinal , Doenças Inflamatórias Intestinais/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Doenças Inflamatórias Intestinais/patologia , Masculino
4.
J Pediatr Gastroenterol Nutr ; 48(1): 55-60, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19172124

RESUMO

OBJECTIVES: We examined the use of complementary and alternative medicine (CAM) at 3 US pediatric medical centers, comparing a group of children with inflammatory bowel disease (IBD) with children presenting with chronic constipation. MATERIALS AND METHODS: Surveys were administered by postal mail and at pediatric IBD centers in San Francisco, Houston, and Atlanta from 2001 to 2003. A comparison group consisting of pediatric patients with chronic constipation also was surveyed. Data were analyzed by t tests and by exact tests of contingency tables. RESULTS: In all, 236 surveys were collected from the IBD group; 126 surveys were collected from the chronic constipation comparison group. CAM therapies were used by 50% in the IBD group and 23% in the chronic constipation group. The overall regional breakdown of CAM use in IBD revealed no differences, although the types of CAM therapy used varied by site. The most commonly used CAM therapies in the IBD group were spiritual interventions (25%) and nutritional supplements (25%). Positive predictors for CAM use in IBD include the patient's self-reported overall health, an increase in the number of side effects associated with allopathic medications, white ethnicity, and parental education beyond high school. CONCLUSIONS: This is the first US study to characterize CAM use in pediatric patients with IBD with another chronic gastrointestinal disorder. CAM use was twice as common with the IBD group compared with the chronic constipation group. Regional variations exist with the types of CAM therapy used. Practitioners should know that half of their pediatric patients with IBD may be using CAM in conjunction with or as an alternative to other treatments and that certain predictors can help identify those using CAM therapies.


Assuntos
Terapias Complementares/estatística & dados numéricos , Doenças Inflamatórias Intestinais/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Constipação Intestinal/terapia , Suplementos Nutricionais , Humanos , Lactente , Preparações de Plantas/uso terapêutico , Terapias Espirituais , Inquéritos e Questionários
5.
Clin Gastroenterol Hepatol ; 6(12): 1361-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18848910

RESUMO

BACKGROUND & AIMS: Few epidemiologic investigations characterize inflammatory bowel disease (IBD) in non-Caucasian children. Our study compared IBD characteristics between African Americans and non-African Americans enrolled in a multicenter pediatric IBD registry with endoscopic- and pathology-based diagnosis. METHODS: The study retrieved data entered from January 2000 to October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community US pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African Americans and non-African Americans in the following categories: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6 y, 6-12 y, or >12 y) at diagnosis or symptom onset; presence of extraintestinal manifestations, Z-scores for height and weight, immunomodulatory therapy, anatomic disease location, and abnormal hemoglobin, albumin, or sedimentation rate at diagnosis. RESULTS: A total of 1406 patients had complete data, 138 (10%) of whom were African American. African Americans more often were older than 12 years of age at diagnosis (52% vs 37%; odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.28-2.59) and symptom onset (46% vs 30%; OR, 1.99; 95% CI, 1.40-2.84); had Crohn's disease (78% vs 59%; OR, 2.36; 95% CI, 1.56-3.58); and had a low hemoglobin level at diagnosis (39% vs 17%; OR, 3.15; 95% CI, 1.92-5.17). CONCLUSIONS: IBD in African American children and adolescents presents more commonly with Crohn's disease and at older ages compared with non-African Americans. Racial/ethnic differences in the epidemiology of IBD, particularly Crohn's disease, among American youths require further investigation.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Fatores Etários , Anemia/epidemiologia , Criança , Pré-Escolar , Etnicidade , Feminino , Humanos , Lactente , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Estados Unidos/epidemiologia
6.
Am J Gastroenterol ; 103(8): 2092-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18796101

RESUMO

BACKGROUND: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis. METHODS: We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient. RESULTS: In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients. CONCLUSIONS: The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.


Assuntos
Doença de Crohn/epidemiologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos
7.
J Pediatr ; 153(5): 651-8, 658.e1-3, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18589450

RESUMO

OBJECTIVE: To investigate the effect of human growth hormone (GH) injections on growth velocity in growth-impaired children with Crohn's disease (CD). STUDY DESIGN: Ten children and adolescents (mean age, 12.6 +/- 4.5 years; 6 males) with CD and poor height growth were treated with open-label recombinant GH, 0.043 mg/kg/day administered via subcutaneous injection, for 1 year. Patients were retrospectively matched with untreated patients (3 comparisons per case) by race, age, sex, and baseline height. Primary endpoint was height velocity; secondary endpoints were disease activity, body composition, and bone density determined by dual-energy x-ray absorptiometry scan. RESULTS: Mean height velocity increased by 5.33 +/- 3.40 (mean +/- standard deviation) cm/year in the GH-treated patients during the year of GH treatment, compared with 0.96 +/- 3.52 cm/year in the comparison group (P = .03). Height z-score increased by 0.76 +/- 0.38 in the treated group, compared with 0.16 +/- 0.40 in the comparison group (P < .01), and weight z-score increased by 0.81 +/- 0.89 in the treated group, compared with 0.00 +/- 0.57 in the comparison group (P < .01). Bone density revealed an increase of 0.31 +/- 0.33 in the lumbar spine z-score (P = .03 vs baseline). CONCLUSIONS: GH treatment increases height velocity and may enhance bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is needed to evaluate the ultimate impact of GH treatment.


Assuntos
Doença de Crohn/terapia , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Adolescente , Adulto , Composição Corporal , Estatura , Densidade Óssea , Criança , Pré-Escolar , Doença de Crohn/metabolismo , Sistema Endócrino , Feminino , Humanos , Masculino , Proteínas Recombinantes/uso terapêutico
8.
J Pediatr Gastroenterol Nutr ; 46(2): 164-71, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18223375

RESUMO

OBJECTIVE: To extend development of a pediatric inflammatory bowel disease (IBD) health-related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables. PATIENTS AND METHODS: Cross-sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age-eligible subjects or visits to participating centers. The survey included generic (Pediatric Quality of Life Inventory) and IBD-specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures. RESULTS: We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well-being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children with higher disease activity scores and other indicators of clinical activity reported lower HRQoL. CONCLUSIONS: This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators.


Assuntos
Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida , Estresse Psicológico , Adolescente , Imagem Corporal , Criança , Doença Crônica , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Ajustamento Social , Inquéritos e Questionários
9.
J Pediatr Gastroenterol Nutr ; 45(1): 56-64, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17592365

RESUMO

BACKGROUND: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition launched a provider and public education campaign in 2002 to raise awareness of gastroesophageal reflux disease (GERD). To determine the effectiveness of campaign messages, we conducted a knowledge, attitudes, and practice styles (KAPS) survey of pediatric providers. Understanding the spectrum of management styles of GERD in children is critical to achieve better health outcomes and reduce health care costs. MATERIALS AND METHODS: The KAPS questionnaire was administered to 6000 randomly selected members of the American Academy of Pediatrics. RESULTS: A total of 1245 members responded; 82% worked in a primary care setting and 18% in subspecialty practices. Overall, 66% of the members order diagnostic testing in routine practice, 54% start testing for GERD in neonates, and 38% start testing after 1 month of age. The most common tests ordered were barium esophagram (45%) and esophageal pH monitoring (37%). GERD treatment with acid suppression before ordering diagnostic testing was a choice of 82% of the respondents. However, 19% believed acid suppression was best achieved by H2 blockers. If acid suppression was indicated, then only 36% followed guideline recommendations for therapy duration and 52% followed guideline recommendations for dosing. Antireflux surgery was recommended only as a last resort by 92%. Overall, 69% of providers believed the amount of GERD-related information available was not enough. Respondents who were not aware of available GERD practice guidelines ranged from 74% to 92%. CONCLUSIONS: Pediatric providers appear to frequently order diagnostic testing and treatment for GERD, yet knowledge about evidence-based GERD management among this random sample appeared limited. Moreover, a significant number of providers were not aware of different guideline publications.


Assuntos
Refluxo Gastroesofágico , Conhecimentos, Atitudes e Prática em Saúde , Pediatria , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Fatores Etários , Criança , Pré-Escolar , Coleta de Dados , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , América do Norte , Inquéritos e Questionários
10.
Cell Rep ; 14(4): 945-955, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26804920

RESUMO

The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Doença de Crohn/microbiologia , Disbiose/microbiologia , Microbiota , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Disbiose/complicações , Disbiose/diagnóstico , Fezes/microbiologia , Humanos , Lactente
11.
Inflamm Bowel Dis ; 11 Suppl 1: S22-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16254479

RESUMO

Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the differentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting. Validated, easy-to-use disease activity indices allow interpretation of results across trials. The use of biomarkers as surrogate clinical endpoints provides reproducibility, ease of statistical handling as a continuous variable, and consistent measurement of response to treatment. Despite these potential advantages, biomarkers of disease activity lack specificity and will need to be validated against clinically meaningful outcomes. Careful subject selection, standardization of disease activity indices, and precise outcome measurement are the keys to continued improvement of the inflammatory bowel disease research process.


Assuntos
Ensaios Clínicos como Assunto , Doenças Inflamatórias Intestinais/tratamento farmacológico , Biomarcadores/análise , Determinação de Ponto Final , Humanos , Fenótipo , Qualidade de Vida , Projetos de Pesquisa , Resultado do Tratamento
12.
Inflamm Bowel Dis ; 11(9): 833-9, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16116318

RESUMO

Probiotics are widely used by patients with Crohn's disease (CD) in an attempt to improve their health, but few controlled studies have been done to evaluate the efficacy of these therapies. We conducted a randomized, placebo-controlled trial of the probiotic Lactobacillus rhamnosus strain GG (LGG) to see if the addition of LGG to standard therapy prolonged remission in children with CD. Concomitant medications allowed in the study included aminosalicylates, 6-mercaptopurine, azathioprine, and low-dose alternate day corticosteroids. Seventy-five children (age range, 5-21 yr) with CD in remission were randomized to either LGG (n=39) or placebo (n=36) and followed for up to 2 years. The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group (P=0.24); 31% (12/39) of patients in the LGG group developed a relapse compared with 6/36 (17%) of the placebo group (P=0.18). The LGG was well tolerated, with a side effect profile comparable with placebo. This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to standard therapy.


Assuntos
Doença de Crohn/tratamento farmacológico , Lactobacillus , Probióticos/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Placebos , Recidiva , Fatores de Tempo , Resultado do Tratamento
14.
Inflamm Bowel Dis ; 10(6): 723-30, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15626889

RESUMO

OBJECTIVES: The objectives of this study were to evaluate the safety, pharmacokinetics, and immunogenicity of CDP571 in pediatric patients with Crohn's disease. METHODS: A single dose of CDP571, 10 mg/kg, was administered by infusion to pediatric patients (aged 6-17 years) with Crohn's disease in a 12-week open-label study. Adverse events were monitored during infusion and throughout the study. Plasma concentrations of CDP571 and standard clinical and laboratory values were assessed. Changes in disease activity were monitored using the Pediatric Crohn's Disease Activity Index (PCDAI). RESULTS: Twenty patients were enrolled and stratified by age: 6 to 13 (n = 9) and 14 to 17 years (n = 11). Fourteen patients experienced adverse events, which were mainly mild or moderate in intensity. The plasma concentration profile was consistent with a half-life of approximately 2 weeks. At Week 4, 4 patients in the 6- to 13-year-old group and 2 patients in the 14- to 17-year-old group had detectable anti-CDP571 antibodies. By Week 2, 7 patients in the 6- to 13-year-old group and 6 patients in the 14- to 17-year-old group had responded to treatment (reduction in PCDAI score >10 points). CONCLUSION: In conclusion, CDP571 was well tolerated among pediatric patients with Crohn's disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/farmacocinética , Criança , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/sangue , Fármacos Gastrointestinais/farmacocinética , Humanos , Masculino , Resultado do Tratamento , Estados Unidos
15.
Epigenetics ; 9(8): 1131-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24937444

RESUMO

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P<0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.


Assuntos
Colite Ulcerativa/genética , Colo/imunologia , Doença de Crohn/genética , Metilação de DNA/imunologia , Mucosa Intestinal/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Epigênese Genética , Feminino , Expressão Gênica , Humanos , Imunidade nas Mucosas , Masculino , Adulto Jovem
16.
Clin Exp Gastroenterol ; 6: 77-83, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23825926

RESUMO

BACKGROUND: The natural history of ulcerative colitis (UC) has been poorly studied in children. METHODS: We performed a retrospective study in children diagnosed with UC with a follow-up. The diagnosis of UC was based on clinical, radiologic, endoscopic, and histologic examinations. We estimated the occurrence of colectomy, proctitis, and extraintestinal manifestations (EIMs) at the onset of the diagnosis and at the end of the study period. RESULTS: We identified 115 UC patients between 1986 and 2003 with a mean age at diagnosis of 10.6 ± 5.1 years. The cumulative rate of colectomy was 4.1% at 1 year, and 16% at 10 years. EIMs were experienced by 20% of the children; 48% had arthritis, 35% had sclerosing cholangitis, and 17% had aphthous stomatitis. Proctitis was noted in 29 patients and it was not associated with an increased risk of colectomy (relative risk = 1.4; 95% CI = 0.7-4.5), and girls were twice more likely to develop proctitis. The pathologic reading for disease extensions was recorded for all children at entry and only 62 children had pathological results at maximum follow-up. At entry, 25% of the children only had ulcerative proctitis (E1) localization, 40% had left-sided UC (E2), and 35% had extensive UC (E3). Among the patients with E1 localization, 20% had progressed to E2 and 80% had progressed to E3; among the patients with E2 localization, 40% had progressed to E3. Age, gender, and EIMs at time of diagnosis were not associated with extension of disease at maximal follow-up. The Z score of body mass index (BMI) of children was significantly higher at the end of the study. At diagnosis, 85% of patients received 5-aminosalicyclic acid, 60% received steroids, and 11% received an immunomodulator. The majority of patients were still using systemic steroids at and after 5 years from their entry date. Only 32 of the 91 children on steroids did not receive an immunomodulator. CONCLUSION: Pediatric UC is associated with high rates of EIMs and colectomy that are not dependent on age, gender, or race, but is associated with a high rate of proctitis among girls. Understanding the clinical course of UC can optimize therapeutic interventions.

17.
Clin Exp Gastroenterol ; 6: 115-21, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23901288

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD)-indeterminate is a subgroup of IBD that has features of both ulcerative colitis (UC) and Crohn's disease (CD). AIMS: To determine the clinical course of IBD-indeterminate in children over a 25 year period. METHODS: We performed a retrospective investigation on children diagnosed with IBD. Diagnosis and disease distribution of IBD was based on clinical, radiologic, endoscopic, and histologic examinations. RESULTS: Four hundred and twenty children diagnosed with IBD between 1986 and 2003 were identified from the IBD registry, 78 (22%) of whom were diagnosed with IBD-indeterminate. The mean age at diagnosis was 9.2 ± 4 years and the mean follow-up period was 4.1 ± 2 years. In 2003, 18 of 78 children (23%) were reclassified by the same physician based on the endoscopic and pathologic findings as follows: eight children with CD, five children with UC, and five children with non-IBD (eg, eosinophilic colitis). During 2011, 20 of the 60 patients who had maintained an IBD-indeterminate diagnosis were located and contacted, and detailed telephone interviews were conducted by the corresponding author. Two patients were reclassified as having CD (10%), one patient was reclassified as having eosinophilic colitis (5%), six patients remained with IBD-indeterminate (30%), and eleven patients (55%) reported a complete resolution of their symptoms. The follow-up period ranged from 10-18 years (mean 12.5 ± 3 years). Children who were reclassified as having CD were significantly younger than those who maintained an IBD-indeterminate diagnosis (6.4 ± 4 years versus11.2 ± 3 years, respectively, P = 0.05). CONCLUSION: Children with IBD-indeterminate remain classified as IBD-indeterminate, or were clinically reclassified as CD or non-IBD, or became asymptomatic as they transitioned into adulthood. The need for IBD-indeterminate classification is of importance, especially when deciding on management and treatment.

18.
Inflamm Bowel Dis ; 18(3): 546-54, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21456045

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has a wide spectrum and variability among different ethnic groups. We aimed to evaluate disease characteristics in the pediatric Hispanic population, which has not been well studied. METHODS: We identified patients <18 years old seen at Texas Children's Hospital (TCH) and diagnosed with IBD between 2004 and 2009. We compared them with their White, African American, and "other" counterparts with regard to their demographics, disease characteristics, and initial therapy. RESULTS: There were a total of 399 patients with IBD: 211 (52.9%) White, 67 (16.8%) African American, 53 (13.3%) Hispanic, and 68 (17%) "other." Crohn's disease (CD) was the most common IBD type among all groups; however, Hispanics had the highest proportion of patients with ulcerative colitis (UC) and IBD-unclassified (IBD-U). There was male predominance in all groups except African Americans. Hispanics had the highest percentage of Medicaid coverage (P < 0.01) and none of the Hispanics had a first-degree relative with IBD. They had a younger age at diagnosis but a similar duration of symptoms prior to diagnosis. Hispanics had less failure to thrive and a higher body mass index (BMI) Z-score. Hispanics with CD more often received systemic steroids while those with UC and IBD-U were more often treated with local steroids (P < 0.01), oral 5-aminosalicylate (P < 0.01), and less often received immunomodulators or biologics (P = 0.05). CONCLUSIONS: We demonstrate differences in disease characteristics between Hispanics and other ethnicities with IBD. Further epidemiologic studies are needed, including longer-term follow-up, to better define the burden of illness in Hispanics.


Assuntos
Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Hispânico ou Latino/estatística & dados numéricos , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Anti-Inflamatórios não Esteroides/uso terapêutico , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Insuficiência de Crescimento/etnologia , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Lactente , Masculino , Medicaid , Mesalamina/uso terapêutico , Estatísticas não Paramétricas , Esteroides/uso terapêutico , Texas/epidemiologia , Estados Unidos , População Branca/estatística & dados numéricos
19.
Inflamm Bowel Dis ; 16(4): 638-44, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19760783

RESUMO

BACKGROUND: The development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD). METHODS: We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age 0-17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry. RESULTS: Mean age at diagnosis was 11.5 +/- 3.8 (standard deviation) years. Median follow-up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications). CONCLUSIONS: Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patient's risk for the development of complicated disease and to determine optimal treatment regimens.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Mucosa Intestinal/patologia , Complicações Pós-Operatórias , Adolescente , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Constrição Patológica , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Seguimentos , Humanos , Incidência , Lactente , Fístula Intestinal/etiologia , Obstrução Intestinal , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
20.
Inflamm Bowel Dis ; 15(1): 63-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18626963

RESUMO

BACKGROUND: Extraintestinal manifestations (EIMs) in pediatric patients with inflammatory bowel disease (IBD) are poorly characterized. We examined the prevalence of EIMs at diagnosis, subsequent incidence, and risk factors for EIMs. METHODS: Data for 1649 patients from the PediIBD Consortium Registry, diagnosed with IBD before 18 years of age (1007 [61%] with Crohn's disease, 471 [29%] with ulcerative colitis, and 171 [10%] with indeterminate colitis), were analyzed using logistic regression, Kaplan-Meier, log rank tests, and Cox models. RESULTS: EIMs were reported prior to IBD diagnosis in 97 of 1649 patients (6%). Older children at diagnosis had higher rates compared with younger children, and arthritis (26%) and aphthous stomatitis (21%) were most common. Among the 1552 patients without EIM at diagnosis, 290 developed at least 1 EIM. Kaplan-Meier estimates of cumulative incidence were 9% at 1 year, 19% at 5 years, and 29% at 15 years after diagnosis. Incidence did not differ by IBD type (P = 0.20), age at diagnosis (P = 0.22), or race/ethnicity (P = 0.24). Arthritis (17%) and osteopenia/osteoporosis (15%) were the most common EIMs after IBD diagnosis. CONCLUSIONS: In our large cohort of pediatric IBD patients, 6% had at least 1 EIM before diagnosis of IBD. At least 1 EIM will develop in 29% within 15 years of diagnosis. The incidence of EIMs both before and after diagnosis of IBD differs by type of EIM and may be slightly higher in girls, but is independent of the type of IBD, age at diagnosis, and race/ethnicity.


Assuntos
Artrite/etiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Estomatite Aftosa/etiologia , Adolescente , Artrite/patologia , Criança , Pré-Escolar , Estudos de Coortes , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Estomatite Aftosa/patologia
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