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The incidence of pediatric ulcerative colitis (UC), a chronic autoinflammatory disease of the colon, is on the rise. Although an increased infiltration of B cells from the peripheral blood into the colon occurs in UC, B-cell trafficking is understudied. We hypothesized that the frequency of circulating plasmablasts (PBs) and their trafficking receptor (TR) expression may be indicative of the location and degree of pathology in pediatric UC.MethodsWe conducted multicolor flow cytometry analyses of circulating IgA+/− PBs and IgA+ memory B cells (MBCs) in pediatric UC patients with remission, mild, moderate, and severe state of disease (n = 12), and healthy pediatric (n = 2) and adult donors (n = 11).ResultsCompared to healthy donors the average frequency of PBs among total peripheral blood lymphocytes is increased 30-fold during severe UC activity, and positively correlates with Pediatric Ulcerative Colitis Activity Index score, C-reactive protein level, and erythrocyte sedimentation rate. A greater percent of PBs in severe patients express the gut-homing receptors α4β7 and CCR10, and the inflammatory homing molecule P-selectin ligand (P-sel lig). The percent of IgA+ MBCs expressing α4β7, however, is reduced. Furthermore, expression of the small intestine TR CCR9 is decreased on α4β7high PBs, and on α4β7high/CCR10high PBs and MBCs in these patients, consistent with preferential cell targeting to the colon.ConclusionsPeripheral blood PBs with a colon-homing phenotype (α4β7/CCR10/P-sel lig) are elevated in children with severe UC. Screening this B-cell subset may provide a complementary approach in monitoring disease activity or therapeutic efficacy in pediatric UC.

Objectives. To assess the relationship between infections and the risk of pediatric-onset inflammatory bowel disease (IBD). Methods. We conducted a nested case-control study of 501 incident cases aged ≤17 years and 9,442 controls who were members of Kaiser Permanente Northern California for at least one consecutive year between 1996 and 2006. IBD was confirmed and the incidence date was adjudicated by pediatric gastroenterologists. Hospitalized infections were identified from the principal diagnosis code of electronic inpatient records. Medications to treat infections were identified during the hospitalization. Conditional logistic regression was used to assess the associations between hospitalized infections, medications, and Crohn’s disease and ulcerative colitis. Results. In the year prior to diagnosis, both hospitalized infection of any system (OR 6.3; 95% CI 1.6–23.9) and hospitalized intestinal infection (OR 19.4; 95% CI 2.6–143.2) were associated with CD. Hospitalized infections of any system were inversely associated with UC after excluding the year prior to diagnosis (OR 0.4; 95% CI 0.2–0.9). No UC case had a hospitalized gastrointestinal infection prior to diagnosis. Conclusion. Infections appear to play opposite roles prior to the diagnosis of CD and UC. Infections may be associated with an increased risk of CD and a decreased risk of UC.

BackgroundAs an important quality measure, the rates of recommended immunizations among immunocompromised inflammatory bowel disease (IBD) patients in community practice have not been well studied.AimsThis study sought to investigate the rates and predictors of recommended immunizations and screening tests among IBD patients receiving anti-tumor necrosis factor (TNF) therapy in a large integrated healthcare organization.MethodsWe conducted a retrospective cohort study of 1401 IBD patients on anti-TNF therapy between 2010 and 2013 within the Kaiser Permanente Northern California healthcare system. The rates of vaccinations and screening tests were quantified, and the associated predictors were investigated.ResultsVaccination rates for influenza and pneumococcus were 43.5 and 24.1%, respectively. The majority of patients (73.7%) received hepatitis B screening and/or vaccine. Patients receiving infliximab had higher rates of pneumococcal vaccine (P = 0.002), hepatitis B screening (P < 0.001), and tuberculin skin test (P < 0.001) compared with patients receiving adalimumab. Older patient age (≥50 years) was associated with higher likelihood of having HBsAg test (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–2.0, P = 0.002), influenza vaccine (OR 2.6 [2.1–3.4], P < 0.001), and pneumococcal vaccine (OR 4.0 [3.0–5.3], P < 0.001). In contrast, older providers (≥50 years) were associated with significantly lower likelihood of their patients’ having hepatitis A and B screening tests, and pneumococcal vaccination.ConclusionsThe rates of immunizations for IBD patients receiving anti-TNF treatment were lower than recommended. Structured reminders for vaccinations and education for both patients and providers (older physicians in particular) may prove beneficial in improving immunization rates among immunocompromised IBD patients.

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.MethodsData 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.ResultsEIMs 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.ConclusionsIn 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.

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. 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. 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. 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.

Background Current knowledge of racial disparities in healthcare utilization and disease outcomes for ulcerative colitis (UC) is limited. We sought to investigate these differences among Caucasian, African American, Asian, and Hispanic patients with ulcerative colitis in Kaiser Permanente, a large integrated health-care system in Northern California. Methods This retrospective cohort study used computerized clinical data from 5,196 Caucasians, 387 African–Americans, 550 Asians, and 801 Hispanics with prevalent UC identified between 1996 and 2007. Healthcare utilization and outcomes were compared at one and five-year follow-up by use of multivariate logistic regression analysis. Results Compared with whites, the male-to-female ratio differed for African–Americans (0.68 vs. 0.91, p  < 0.01) and Asians (1.3 vs. 0.91, p  < 0.01). Asians had fewer co-morbid conditions ( p  < 0.01) than whites, whereas more African–Americans had hypertension and asthma ( p  < 0.01). Use of immunomodulators did not differ significantly among race and/or ethnic groups. Among Asians, 5-ASA use was highest ( p  < 0.05) and the incidence of surgery was lowest ( p  < 0.01). Prolonged steroid exposure was more common among Hispanics ( p  < 0.05 at 1-year) who also had more UC-related surgery ( p  < 0.01 at 5-year) and hospitalization (<0.05 at 5-year), although these differences were not significant in multivariate analysis. Conclusions In this population of UC patients with good access to care, overall health-care utilization patterns and clinical outcomes were similar across races and ethnicity. Asians may have milder disease than other races whereas Hispanics had a trend toward more aggressive disease, although the differences we observed were modest. These differences may be related to biological factors or different treatment preferences.

BackgroundThe development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD).MethodsWe 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.ResultsMean 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).ConclusionsStrictures, 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. (Inflamm Bowel Dis 2009;)

Background The majority of studies that report early life risk factors for pediatric-onset inflammatory bowel disease (IBD) do not account for potential confounding, which can lead to spurious associations and incorrect inferences. Aims To assess the relationship between prenatal and perinatal characteristics and the risk of pediatric-onset IBD accounting for potential confounding. Methods We conducted a nested case–control study of 189 cases aged ≤18 years and 3,080 age- and membership-matched controls born at a Kaiser Permanente Northern California facility between 1984 and 2006. The cases were diagnosed with IBD between 1996 and 2006 and diagnosis was confirmed by chart review. We obtained prenatal and perinatal characteristics from the electronic clinical records of the mother and child. Conditional logistic regression was used to assess the associations between these factors and risk of incident IBD, Crohn’s disease, and ulcerative colitis. Results In analyses accounting for confounding, maternal IBD (odds ratio [OR] 5.1, 95 % confidence interval [CI] 2.0–12.9) and white race (OR 2.3, 95 % CI 1.6–3.2) were the only factors statistically associated with pediatric-onset IBD. Maternal respiratory infection during pregnancy (OR 2.0, 95 % CI 1.0–4.0), age < 20 years (OR 2.0, 95 % CI 0.8–4.7) and gestational hypertension (OR 1.7, 95 % CI 1.0–2.7) were associated with pediatric-onset IBD, but did not achieve statistical significance. Conclusions Maternal history of IBD and race were the only characteristics of those that we examined that were associated with the development of pediatric IBD in this well-documented population of cases and matched controls.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non - vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Information on infliximab use in a community setting is important to understand patterns of medication use and to anticipate and plan for costs associated with the drug. We sought to understand predictors of initiation and discontinuation of infliximab in the community-based setting of Kaiser Permanente, Northern California, which provides integrated care to its members.MethodsThe cohort study was set during 1998–2006. Predictors of initiation were assessed among 494 Crohn's disease (CD) patients who initiated infliximab and 2470 CD patients who did not initiate infliximab (controls). Data were obtained through linkage of computerized clinical information and were analyzed using logistic regression and Cox survival analysis.ResultsInfliximab infusions have increased rapidly since 2001, with no evidence of leveling off. Initiators were appreciably younger than controls (P < 0.001), but were similar to controls with respect to sex and race/ethnicity. The presence of at least 1 comorbidity was related to a modest increase in the risk of initiating (compared with none: 1 comorbidity, odds ratio [OR] = 1.52 with 95% confidence interval [CI] 1.16–2.00; 2 comorbidities, OR = 1.38 with CI 0.89–2.13). By 3 years after initiating, only 20% of patients remained on infliximab.ConclusionsIn a community-based setting infliximab use has steadily increased. Age and comorbidity are associated with initiation, but sex and race/ethnicity are not. More information is needed to determine why, in this community-based setting, a large number of patients on infliximab discontinued their treatment.