RESUMEN
Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.
Asunto(s)
Calbindina 2/genética , Predisposición Genética a la Enfermedad , Enfermedades Inflamatorias del Intestino/genética , Subtipo EP4 de Receptores de Prostaglandina E/genética , Negro o Afroamericano/genética , Anciano , Anciano de 80 o más Años , Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Enfermedades Inflamatorias del Intestino/patología , Masculino , Herencia Multifactorial/genética , Polimorfismo de Nucleótido Simple/genética , Población Blanca/genética , Secuenciación Completa del GenomaRESUMEN
BACKGROUND AND AIMS: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD. METHODS: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 U.S. sites from 2019-2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61-180 days, 181-365 days and >365 days. RESULTS: We enrolled 869 participants (mean age at diagnosis 13.1 years, 52% male, 57% Crohn's disease (CD), 34% ulcerative colitis (UC), 8% Hispanic, 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs. UC (OR 2.6, 95% CI 1.9-3.5), 2 or more other health conditions (OR 1.7, 95% CI 1.1-2.7), and longer travel time to clinic [(> 1 hour (OR 1.7, 95% CI 1.2-2.4), > 2 hours (OR 1.8, 95% CI 1.2-2.9) each vs<30 minute]. There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust. CONCLUSIONS: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.
RESUMEN
INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.
Asunto(s)
Adalimumab , Índice de Masa Corporal , Enfermedad de Crohn , Quimioterapia Combinada , Infliximab , Metotrexato , Factor de Necrosis Tumoral alfa , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Masculino , Femenino , Infliximab/uso terapéutico , Adalimumab/uso terapéutico , Niño , Adolescente , Metotrexato/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Insuficiencia del Tratamiento , Fármacos Gastrointestinales/uso terapéutico , Obesidad Infantil/complicaciones , Obesidad Infantil/tratamiento farmacológicoRESUMEN
OBJECTIVES: This study aims to characterize pediatric inflammatory bowel disease (IBD) patients who change diagnosis and describe the characteristics of that change. METHODS: A retrospective study was conducted on pediatric IBD patients from the ImproveCareNow (ICN) multicenter international cohort from 2007 to January 2019. Primary outcome was change in diagnosis after the first four visits. Other variables included demographics, diagnostics, disease characteristics, and timing. RESULTS: 6.1% of 18,055 patients aged 1-20 years changed diagnosis. Median time between the baseline visit and first diagnosis change was 0.9 years. Change in diagnosis occurred in 257/12,178 (2.1%) patients with Crohn's disease (CD), 347/4758 (7.3%) patients with ulcerative colitis (UC), and 495/1119 (44.2%) patients with IBD-Unclassified (IBD-U). In multivariable analysis, initial diagnosis of IBD-U and longer follow-up times were associated with greater odds of a diagnosis change. CONCLUSION: IBD-U initial diagnosis and longer follow-up were associated with increased diagnosis change risk. The most common change was reclassification to CD. Disease activity, moderate malnutrition, and presence of EIMs were not associated with change in diagnosis.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Desnutrición , Humanos , Niño , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Colitis Ulcerosa/diagnósticoRESUMEN
BACKGROUND: Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic. METHODS: We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation. RESULTS: Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8-3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC ( P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date. CONCLUSIONS: Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.
Asunto(s)
Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Adolescente , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Adalimumab/uso terapéutico , Factores Biológicos , Productos Biológicos/uso terapéuticoRESUMEN
INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.
Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Complejo de Antígeno L1 de Leucocito , Adolescente , Teorema de Bayes , Niño , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/dietoterapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/dietoterapia , Dieta , Heces/química , Humanos , Inflamación/complicaciones , Inflamación/dietoterapia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/dietoterapia , Complejo de Antígeno L1 de Leucocito/análisis , Medicina de PrecisiónRESUMEN
OBJECTIVE: Transition to adult IBD care continues to be a challenge. Efficacious models of improving transition to adult care in the United States are lacking. We present data from a pilot, prospective, non-randomized, intervention implemented at IBD centers in the Midwest and Southeast United States. DESIGN AND METHODS: Adolescents and young adults (AYAs; 16-20 years) with IBD and their parents completed a 4- to 5-month transition program (1 in-person group session; 4 individual telehealth sessions). Primary outcomes were feasibility (i.e., recruitment, retention, fidelity) and acceptability (i.e., program satisfaction). Secondary outcomes were changes in transition readiness, self-management skill acquisition, perceived readiness to transfer to adult care, and disease knowledge. RESULTS: The study exceeded goals for recruitment (target N = 20; actual: 36) and retention (target: 80%; actual: 86.11%). On average, it took participants 20.91 ± 3.15 weeks to complete our 4- to 5-month intervention and there were no deviations from the study protocol. Participant ratings for overall program satisfaction, perceived helpfulness, and program length and format were positive. Increases in transition readiness, t(30) = 8.30, d = 1.49, p < .001, self-management skill acquisition, t(30) = 3.93, d = 0.70, p < .001, and disease knowledge, t(30) = 8.20, d = 1.58, p < .001 were noted. AYA- and parent-perceived transfer readiness also improved (p's < .05; d's = 0.76-1.68). CONCLUSIONS: This article presents feasibility and acceptability data for a 4- to 5-month transition intervention. Improvements in AYA transition readiness, self-management skill acquisition, IBD knowledge, and AYA/parent perceived transfer readiness were also observed.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Telemedicina , Transición a la Atención de Adultos , Adolescente , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Estudios Prospectivos , Sudeste de Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Noninvasive and accurate methods to monitor inflammatory bowel disease are required. As a planned ancillary study of the prospective ImageKids cohort, we aimed to assess the performance of fecal calprotectin (FC) with comparison to 3 fecal inflammatory markers; S100A12 (FA12), tumor pyruvate kinase isoenzyme type M2 (FM2PK) and fecal osteoprotegerin (FOPG) as indicators of a number of disease characteristics. METHODS: The ImageKids study was a multicenter study designed to develop 2 magnetic resonance enterography-based measures for children with Crohn disease (6-18 years old). All patients underwent magnetic resonance enterography, a complete ileocolonoscopic evaluation and provided a fecal sample. Fecal samples were assay for FC, FA12, FM2PK, and FOPG by ELISA. RESULTS: One-hundred fifty-six children provided 190 fecal samples. Median (interquartile range) for fecal makers were FC, 602 (181-1185) µg/g; FA12, 21 (3-109) µg/g; FM2PK, 16 (2-20) U/mL; and FOPG, 125 (125-312) µg/g. All markers correlated with simple endoscopic severity index for Crohn disease and with other constructs of disease activity, but FC had the highest overall correlations. FA12, however, predicted mucosal healing with significantly higher specificity (87% vs 70%, Pâ=â0.004) and equivalent sensitivity (91% vs 90%) compared to FC. CONCLUSION: This study has confirmed that FC is useful, and overall best, marker to monitor mucosal inflammation in inflammatory bowel disease. FA12, however, appears to be a more suitable maker for prediction of mucosal healing in children.
Asunto(s)
Enfermedad de Crohn , Adolescente , Biomarcadores/análisis , Niño , Colonoscopía , Enfermedad de Crohn/diagnóstico , Heces/química , Humanos , Inflamación , Complejo de Antígeno L1 de Leucocito , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Deficits in the preparation of patients with inflammatory bowel disease (IBD) who are transitioning to adult care are known yet studies presenting outcome data of transition interventions in IBD are lacking. We present data evaluating the impact of a transition coordinator on behavioral and clinical transition outcomes. METHODS: A retrospective chart review identified 135 patients who had met with our transition coordinator and completed the Transition Readiness Assessment Questionnaire before, and 1 year after, the intervention. Changes in transition readiness, self-management skill acquisition, and clinical outcomes (eg, number of patients transferred vs "bounced back" to pediatrics, percentage of patients over age 21, changes in disease remission) were examined and compared with patients who received no intervention. RESULTS: Intervention participants demonstrated a significant increase in transition readiness, F(1, 134)â=â24.34, Pâ<â0.001, and self-management skill acquisition, F(1, 134)â=â5.61, Pâ<â0.05. The percentage of patients in remission significantly increased from pre- to post-intervention, χ(134)â=â9.03, Pâ<â0.01. There were no significant changes in the comparison population (Psâ>â0.05). Following implementation of our programming, the percentage of patients over age 21 decreased by 33.07%. CONCLUSIONS: A 1-time transition coordinator-led intervention improved adolescent transition readiness and acquisition of self-management skills. The proportion of young adult patients retained in pediatric care was reduced. Benefits of hiring a transition coordinator are discussed.
Asunto(s)
Enfermedades Inflamatorias del Intestino/terapia , Autocuidado , Transición a la Atención de Adultos , Adolescente , Femenino , Humanos , Masculino , Registros Médicos , Estudios Retrospectivos , Medicina Estatal , Encuestas y Cuestionarios , Reino Unido , Adulto JovenRESUMEN
OBJECTIVES: The gut microbiome is believed to play a role in the susceptibility to and treatment of Clostridium difficile infections (CDIs). It is, however, unknown whether the gut microbiome is also affected by asymptomatic C difficile colonization. Our study aimed to evaluate the fecal microbiome of children based on C difficile colonization, and CDI risk factors, including antibiotic use and comorbid inflammatory bowel disease (IBD). METHODS: Subjects with IBD and non-IBD controls were prospectively enrolled from pediatric clinics for a biobanking project (nâ=â113). A fecal sample was collected from each subject for research purposes only and was evaluated for asymptomatic toxigenic C difficile colonization. Fecal microbiome composition was determined by 16S rRNA sequencing. RESULTS: We found reduced bacterial diversity and altered microbiome composition in subjects with C difficile colonization, concurrent antibiotic use, and/or concomitant IBD (all Pâ<â0.05). Accounting for antibiotic use and IBD status, children colonized with C difficile had significant enrichment in taxa from the genera Ruminococcus, Eggerthella, and Clostridium. Children without C difficile had increased relative abundances of Faecalibacterium and Rikenellaceae. Imputed metagenomic functions of those colonized were enriched for genes in oxidative phosphorylation and beta-lactam resistance, whereas in the subjects without C difficile, several functions in translation and metabolism were over-represented. CONCLUSIONS: In children, C difficile colonization, or factors that predispose to colonization such as antibiotic use and IBD status were associated with decreased gut bacterial diversity and altered microbiome composition. Averting such microbiome alterations may be a method to prevent or treat CDI.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium/microbiología , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Alabama , Baltimore , Niño , Preescolar , Heces/microbiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND & AIMS: Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. METHODS: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression. RESULTS: The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%. Most surgeries occurred within 3 years from diagnosis. The only predictor of surgery was disease behavior at diagnosis. CD with inflammatory behavior had the lowest risk of surgery compared to stricturing disease, penetrating disease, or both. We associated slowing of disease progression to stricturing or penetrating disease (but not surgery) with early use of biologics, but this effect only became evident after 5 years of disease. Our results indicate that biologics slow disease progression over time (hazard ratio, 0.85; 95% CI, 0.76-0.95). CONCLUSIONS: In an analysis of data from a registry of pediatric patients with CD, we found that among those with significant and progressing disease at or shortly after presentation, early surgery is difficult to prevent, even with early use of biologics. Early use of biologics (<3 mo of diagnosis) can delay later disease progression to stricturing and/or penetrating disease, but this affect could become evident only years after initial management decisions are made.
Asunto(s)
Productos Biológicos/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Progresión de la Enfermedad , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10-8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10-6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. CONCLUSIONS: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.
Asunto(s)
Negro o Afroamericano/genética , Moléculas de Adhesión Celular Neuronal/genética , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Predisposición Genética a la Enfermedad/genética , Cadenas HLA-DRB1/genética , Proteínas Represoras/genética , Ubiquitina Tiolesterasa/genética , Adenilil Ciclasas/genética , Estudios de Casos y Controles , Proteínas Ligadas a GPI/genética , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Cadenas alfa de HLA-DQ/genética , Humanos , Subunidad p40 de la Interleucina-12/genética , Canal de Potasio KCNQ2/genética , Polimorfismo de Nucleótido Simple , Receptores CXCR6 , Receptores de Quimiocina/genética , Receptores de Interleucina/genética , Subtipo EP4 de Receptores de Prostaglandina E/genética , Receptores Virales/genética , Nexinas de Clasificación/genética , Tenascina/genética , Población Blanca/genéticaRESUMEN
The treatment goal for children suffering from inflammatory bowel disease has been evolving with biologic therapies like anti-tumor necrosis factor agents assuming a more central role in treatment of more aggressive and extensive phenotype. Earlier introduction of anti-tumor necrosis factor agents have shown to be more effective and may even alter the natural history of inflammatory bowel disease. Development of anti-drug antibodies, however, limits long-term usage and leads to dose adjustment in almost half of patients treated with these medications. One of the strategies to minimize the development of anti-drug antibodies has been concomitant use of immunomodulator medications, resulting in fewer infusion reactions and sustained trough levels, potentially lowering the need for dose adjustments. Balanced with these benefits of optimized dosing and likely more sustained response, however, is the concern about increased risk of complications, such as infections and malignancies. The current manuscript reviews the available pediatric literature regarding efficacy, safety, and side effect profile of combination (immunomodulator and biologics) therapy in pediatric Crohn disease and ulcerative colitis, with particular emphasis on cost constraints, and recommendations for selection of patients who would benefit most from combination therapy.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Niño , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/economía , Quimioterapia Combinada/métodos , Gastroenterología , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/economía , Selección de Paciente , Factores de Riesgo , Sociedades Médicas , Estados UnidosRESUMEN
The primary aim of this Clinical Report by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal guidance to pediatric gastroenterologists and clinicians, health systems, and insurance payers regarding home- and office-based infusions for biologic therapies in pediatric inflammatory bowel disease. Patients in North America are increasingly denied coverage by payers based on "place of service" codes at hospital-based infusion units where the treating clinicians primarily provide care. A task force with topic expertise generated 8 best practice recommendations to ensure quality of care for pediatric patients with inflammatory bowel disease receiving non-hospital-based biologic infusions. Pragmatic considerations discussed in this report include patient safety, pediatric-trained nurse availability, care coordination, patient-centeredness, shared liability, administrative support, clinical governance, and costs of care.
Asunto(s)
Productos Biológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Garantía de la Calidad de Atención de Salud/métodos , Calidad de la Atención de Salud/normas , Productos Biológicos/normas , Niño , Humanos , América del Norte , Sociedades Médicas , Estados UnidosRESUMEN
OBJECTIVES: Although magnetic resonance enterography (MRE) can accurately reflect ileal inflammation in pediatric Crohn disease (CD), there are no pediatric data on the accuracy of MRE to detect upper gastrointestinal tract (UGI) lesions. We aimed to compare MRE and esophagogastroduodenoscopy (EGD) in detecting the spectrum and severity of UGI disease in children. METHODS: This is an ancillary study of the prospective multi-center ImageKids study focusing on pediatric MRE. EGD was performed within 2 weeks of MRE (at disease onset or thereafter) and explicitly scored by SES-CD modified for the UGI and physician global assessment. Local and central radiologists scored the UGI region of the MRE blinded to the EGD. Accuracy of MRE compared with EGD was examined using correlational coefficients (r) and area under receiver operating characteristic curves (AUC). RESULTS: One hundred and eighty-eight patients were reviewed (mean age 14â±â1 years, 103 [55%] boys); 66 of 188 (35%) children had macroscopic ulcerations on EGD (esophagus, 13 [7%]; stomach, 34 [18%]; duodenum, 45 [24%]). Most children had aphthous ulcers, but 10 (5%) had larger ulcers (stomach, 2 [1%]; duodenum, 8 [4%]). There was no agreement between local and central radiologists on the presence or absence of UGI inflammation on MRE (Kappaâ=â-0.02, Pâ=â0.71). EGD findings were not accurately detected by MRE, read locally or centrally (râ=â-0.03 to 0.11, Pâ=â0.18-0.88; AUCâ=â0.47-0.55, Pâ=â0.53-1.00).No fistulae or narrowings were identified on either EGD or MRE. CONCLUSIONS: MRE cannot reliably assess the UGI in pediatric CD and cannot replace EGD for this purpose.
Asunto(s)
Enfermedad de Crohn/diagnóstico , Endoscopía del Sistema Digestivo/métodos , Imagen por Resonancia Magnética/métodos , Adolescente , Enfermedad de Crohn/patología , Duodeno/patología , Esófago/patología , Femenino , Humanos , Masculino , Estudios Prospectivos , Estómago/patologíaRESUMEN
OBJECTIVES: The primary objective was to investigate the mediating effects of patient-perceived medication adherence barriers in the relationship between gastrointestinal symptoms and generic health-related quality of life (HRQOL) in adolescents with inflammatory bowel disease (IBD). The secondary objective explored patient health communication and gastrointestinal worry as additional mediators with medication adherence barriers in a serial multiple mediator model. METHODS: The Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms, Medicines, Communication, Gastrointestinal Worry, and Generic Core Scales were completed in a 9-site study by 172 adolescents with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and perceived medication adherence barriers were tested for bivariate and multivariate linear associations with HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of perceived medication adherence barriers as an intervening variable between gastrointestinal symptoms and HRQOL. RESULTS: The predictive effects of gastrointestinal symptoms on HRQOL were mediated in part by perceived medication adherence barriers. Patient health communication was a significant additional mediator. In predictive analytics models utilizing multiple regression analyses, demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and perceived medication adherence barriers significantly accounted for 45, 38, and 29 percent of the variance in HRQOL (all Ps < 0.001), respectively, demonstrating large effect sizes. CONCLUSIONS: Perceived medication adherence barriers explain in part the effects of gastrointestinal symptoms on HRQOL in adolescents with IBD. Patient health communication to healthcare providers and significant others further explain the mechanism in the relationship between gastrointestinal symptoms, perceived medication adherence barriers, and HRQOL.
Asunto(s)
Enfermedades Gastrointestinales/psicología , Enfermedades Inflamatorias del Intestino/psicología , Cumplimiento de la Medicación/psicología , Calidad de Vida/psicología , Adolescente , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Masculino , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: This multi-site study examines patient, parent, and pediatric provider perspectives on what is most important for successful transition. DESIGN AND METHODS: Using the Transition Readiness Assessment Questionnaire, 190 participants recruited from two pediatric IBD centers selected the top five skills they considered "most important for successful transition." Rankings were summarized and compared by group. RESULTS: While patients, parents, and clinicians all identified "calling the doctor about unusual changes in health" and "taking medications correctly and independently" as being important, each stakeholder group qualitatively and statistically differed in terms of transition readiness skills emphasized. Patients endorsed "calling the doctor about unusual changes in health" and "being knowledgeable about insurance coverage," as being most important to successful transition while parents emphasized health monitoring and problem solving. Pediatric providers emphasized adherence to treatment and reporting unusual changes in health. There were statistically significant differences in endorsement rates across participants for seven transition readiness skills. Patients agreed with providers 80% of the time and with their parents 40% of the time. Parent-provider agreement was 60%. CONCLUSIONS: Although there was some overlap across groups, areas of emphasis differed by informant. Patients emphasized skills they need to learn, parents emphasized skills they most likely manage for their children, and providers emphasized skills that directly impact their provision of care. PRACTICE IMPLICATIONS: Patient, parent, and provider beliefs all need to be considered when developing a comprehensive transition program. Failure to do so may result in programs that do not meet the needs of youth with IBD.
Asunto(s)
Continuidad de la Atención al Paciente/organización & administración , Enfermedades Inflamatorias del Intestino/terapia , Padres/psicología , Autocuidado/psicología , Transición a la Atención de Adultos/organización & administración , Adolescente , Femenino , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Enfermedades Inflamatorias del Intestino/psicología , Masculino , Apoyo SocialRESUMEN
Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.
Asunto(s)
Cuidados Posteriores/métodos , Enfermedad de Crohn/cirugía , Cuidados Posoperatorios/métodos , Prevención Secundaria/métodos , Niño , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/etiología , Enfermedad de Crohn/prevención & control , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Recurrencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD. This latter possibility is beyond the scope of this review article, but does need to be considered in anyone with elevated liver function tests. This review is provided as a clinical summary of some of the major hepatic issues that may occur in patients with IBD.