The psychosocial functioning of caregivers of adolescents managing inflammatory bowel disease (IBD) has been understudied; yet, poor caregiver functioning can place youth at risk for compromised disease management. The current study addressed this limitation by examining a sample of caregivers of adolescents with IBD. Study aims included: 1) document rates of paediatric parenting stress, 2) identify associated sociodemographic predictors of parenting stress, and 3) compare previously published rates of parenting stress to those within other paediatric chronic conditions, including cancer, type 1 diabetes, obesity, sickle cell disease, bladder exstrophy.
Caregivers of adolescents with an IBD diagnosis (Mage = 15.4±1.4, 44.4% female, 88.7% Caucasian) and receiving tertiary care within a gastroenterology clinic (N = 62) completed the Pediatric Inventory for Parents (PIP) as a measure of paediatric parenting stress with Frequency and Difficulty as PIP subscales. Paediatric gastroenterologists provided disease severity assessments.
Adolescents with IBD were experiencing relatively mild disease activity. Bivariate correlations revealed that PIP-Difficulty was positively associated with Crohn’s disease severity (r = 0.38, p < 0.01). Caregiver age was negatively associated with the frequency of parenting stress total (r = −.25, p = .05) and communication scores (r = −.25, p <.05). The frequency and difficulty of parenting stressors within the IBD sample were similar to rates within type 1 diabetes, but were significantly lower to rates identified in other paediatric chronic conditions.
Caregivers of adolescents with IBD seem to experience low rates of parenting stress when their adolescents are receiving outpatient care and during phases of IBD relative inactivity. The sociodemographic characteristics of IBD families (i.e., primarily Caucasian, well-educated, and higher socioeconomic status) likely encourage greater access to financial and psychosocial resources, which may aid in promoting more optimal stress management.
Inflammatory bowel disease; parenting distress; adolescence; Pediatric Inventory for Parents; sociodemographics
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization.
Approximately 20-25% of all IBD cases have an onset in childhood or adolescence. Beyond disease severity, little is known regarding determinants of health-related quality of life (HRQOL) in this population. This study aimed to identify behavioral correlates of HRQOL and examine behavioral/emotional dysfunction (e.g., internalizing/externalizing symptoms) as the mechanism through which disease severity impacts HRQOL.
62 adolescents (M = 15.47 years, SD = 1.42) with IBD (79% Crohn’s disease) and their parents were recruited from one of two pediatric IBD specialty clinics located in the Midwest or Northeast region of the United States. Participants completed a demographic questionnaire, the Youth Self-Report version of the Child Behavior Checklist, and the IMPACT-III. Disease severity was calculated for Crohn’s disease and ulcerative colitis using standardized measures.
Greater disease severity, externalizing symptoms, and internalizing symptoms were all independently associated with lower HRQOL. Furthermore, internalizing symptoms partially mediated the relationship between disease activity and HRQOL, reducing the effect of disease severity on HRQOL from 22% to 9% in the mediation model. A Sobel test examining the significance of the indirect effect of disease severity on HRQOL via behavioral dysfunction was marginally non-significant (p = .053).
Non-disease specific variables (e.g., behavioral dysfunction) play an important role in impacting HRQOL. Behavioral dysfunction serves as the mechanism through which disease severity partially impacts HRQOL. Continued research to identify other predictors of HRQOL in pediatric IBD will greatly enhance our future ability to design interventions to improve HRQOL and maximize health outcomes.
Inflammatory Bowel Disease; Adolescents; Quality of Life; Behavioral Dysfunction
The objective of this study was to examine the relative contributions of both parental and adolescent functioning to family functioning in adolescent patients with inflammatory bowel disease (IBD) and their families. Participants were 45 adolescents (27 male, 18 female) 13–17 years old (M = 15.41 years, SD = 1.32) with IBD and their parents. Families completed measures of patient behavioral functioning and depression, parent distress and family functioning. Disease severity assessments were completed via data provided by patients’ gastroenterologists. Results indicated that parent-reported patient behavioral problems accounted for a significant 26% of variance in family functioning. Post-hoc analysis revealed that externalizing behavior problems accounted for the majority of this variance compared to internalizing behavior problems. These results suggest that externalizing problems may have a more significant impact on these families than previous research indicates. Moreover, externalizing behaviors may significantly impact family adaptation and should be taken into consideration during routine clinical care. Further research is needed to replicate and expand upon these findings.
Inflammatory bowel disease; Family functioning; Behavior; Distress; Internalizing; Externalizing
The purpose of this study was to examine the relationship of oral medication adherence and perceived adherence barriers with disease severity in a sample of adolescents with IBD.
Participants included 62 adolescents, aged 13–17 years, diagnosed with IBD and their parents. Measures of parent- and patient-rated oral medication adherence and related barriers, behavioral and emotional functioning per parent- and self-report, and disease severity per physician reported medical chart data were obtained.
Fifteen percent of the sample reported clinically elevated depressive symptoms and 24% reported clinically elevated internalizing behavioral problems. Number of reported adherence barriers was 2.6 ± 1.5, and no participants reported zero barriers. Parental ratings of medication adherence (t = −2.11, p < .05) and perceived barriers to adherence (t = 2.05, p < .05) significantly predicted disease severity after statistically controlling for the contributions of behavioral and disease parameters to disease severity.
Results suggest that oral medication adherence and perceived adherence barriers are significantly related to disease severity in adolescents with IBD. These patients also may be at risk for increased behavioral and emotional problems which may impact health outcomes as well. Clinicians should make particular efforts to attend to medication adherence issues with their patients. Working with patients and families to develop solutions for eliminating adherence barriers might result in better disease outcomes.
Adherence; disease severity; inflammatory bowel disease; behavior; Barriers; Crohn’s disease; Ulcerative colitis
To examine the mediating role of youth depressive symptoms in the relationship between parent distress and youth health-related quality of life (HRQOL) in a sample of adolescents with inflammatory bowel disease (IBD).
Sixty-two adolescents, aged 13-17 years, with a confirmed diagnosis of IBD completed assessments of depressive symptoms and HRQOL. Each adolescent’s primary caregiver completed a measure of parent stress related to their child’s illness. Pediatric gastroenterologists provided data for disease severity assessments.
Multiple regression analyses revealed that adolescent depressive symptoms fully mediated the relationship between parent distress and several dimensions of HRQOL (i.e., General Well-Being, Emotional Functioning, Social Functioning, and Total HRQOL). Moreover, mediation was observed after statistically controlling for the impact of disease severity, IBD diagnosis, and significant demographic parameters on HRQOL.
Findings suggests that adolescent depressive symptoms may serve as the mechanism through which parent distress is linked to poorer HRQOL in adolescents with IBD. Close monitoring of parent illness-related distress and adolescent depressive symptoms as well as clinical interventions targeting these factors, are needed to promote optimal outcomes in adolescents with IBD.
Inflammatory Bowel Disease; Adolescents; Quality of Life; Parent Distress; Depression
Background and Aims
Few epidemiological 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 multi-center pediatric IBD registry with endoscopic- and pathology-based diagnosis.
The study retrieved data entered from January 2000–October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community U.S. pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African-Americans and non-African-Americans in: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6y, 6–12y or >12y) 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.
1,406 patients had complete data, 138 (10%) of whom were African-American. African-Americans more often: were >12y of age at diagnosis (52% vs. 37%, OR 1.82, 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); had low hemoglobin at diagnosis (39% vs. 17%, OR 3.15, 95% CI 1.92–5.17).
IBD in African-American children and adolescents presents more commonly with CD and at older ages compared to non-African-Americans. Racial/ethnic differences in the epidemiology of IBD, particularly CD, among American youths require further investigation.
The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD1. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 × 10−9), 22q12 (rs2412973, P = 1.55 × 10−9), 10q22 (rs1250550, P = 5.63 × 10−9), 2q37 (rs4676410, P = 3.64 × 10−8) and 19q13.11 (rs10500264, P = 4.26 × 10−10). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn’s disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.
The development of disease complications is poorly characterized in pediatric patients with Crohn’s disease (CD).
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.
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).
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.
abscess; fistula; non-inflammatory disease; complicated disease; children; adolescence; outcomes; database; registry; inflammatory bowel disease
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.
Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intra-cellular IFN-γ/IL-4 cytokine production to investigate CD4+, Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn’s disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (p < 0.0005); however, no correlation was found between age, clinical end points, %CD4+, or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood.
The objective of this study was to examine patient- and parent-perceived factors that impact adherence to inflammatory bowel disease treatment using a qualitative descriptive individual interview approach. Sixteen adolescents and their parents were recruited from May through August 2007 and interviewed about medication adherence using an open-ended semi-structured interview format. Interviews were audio recorded, transcribed, and coded into themes. Parent-child dyads identified forgetting, interfering activities, parent-child conflict and oppositional behaviour, and inadequate planning for treatment as challenges to adherence. Participants reported that family support and good parent-child relationships, routines, monitoring and reminding, and organizational tools such as pill boxes facilitated treatment adherence. Other issues that emerged included immediacy of treatment effects and parent-adolescent responsibility for treatment. Patients and parents experience a number of challenges related to adherence within behavioural, educational, organizational, and health belief domains. Behavioural interventions should focus on these issues, reduction of perceived barriers, and effective transition of responsibility for treatment adherence. Future research considerations are discussed.
Adolescent Health; Bowel Disease; Compliance; Chronic Disease Management
Objective To examine perceived barriers to medication adherence in inflammatory bowel disease (IBD) treatment and their relationship with adherence using a combined forced choice and semi-structured interview assessment approach. Methods Sixteen adolescents with IBD and their parents participated in an open-ended interview regarding adherence barriers and completed quantitative measures of adherence, barriers to treatment, and disease severity. Results The most commonly identified barriers to adherence were forgetting, interference with other activities, difficulty swallowing pills, and not being at home. Number of reported barriers was positively correlated with objective nonadherence for 6-MP/azathioprine. Nonadherence frequency was 42% for 6-MP/azathoprine and 50% for 5-ASA medications. Conclusions Using a combined assessment approach, patients and parents reported several barriers to treatment adherence that are appropriate for clinical intervention. This is critical given the significant medication nonadherence observed in this sample and the relationship between total number of barriers and disease management problems.
adherence; barriers; compliance; inflammatory bowel disease; medication
Genome-wide association studies (GWAS) and candidate gene studies in ulcerative colitis (UC) have identified 18 susceptibility loci. We conducted a meta-analysis of 6 UC GWAS, comprising 6,687 cases and 19,718 controls, and followed-up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P<5×10-8), increasing the number of UC associated loci to 47. After annotating associated regions using GRAIL, eQTL data and correlations with non-synonymous SNPs, we identified many candidate genes providing potentially important insights into disease pathogenesis, including IL1R2, IL8RA/B, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease (IBD) risk loci is now 99, including a minimum of 28 shared association signals between Crohn’s disease (CD) and UC.
Background and Aims
Pediatric Crohn’s disease (CD) is associated with deficits in growth, lean mass (LM), and fat mass (FM). This study assessed changes in height and body composition in children and adolescents with CD following diagnosis, and identified determinants of these changes.
Whole body LM and FM were assessed using DXA in 78 CD subjects at diagnosis and 6, 12, and a median of 43 (range 24–63) months later. Race- and sex-specific Z-scores for lean mass (LM-ht-Z) and fat mass (FM-ht-Z) relative to height were derived using reference data in >900 controls. Serum cytokines and growth factors were measured and quasi-least squares regression was used to identify determinants of changes in height and body composition Z-scores.
LM-ht-Z and FM-ht-Z (both p<0.005) improved significantly following diagnosis; however, females had persistent LM deficits vs. controls (−0.50 ± 1.02, p<0.05) at the final visit. Serum interleukin-6, TNF-α, and lipopolyscaccharide binding protein (LBP) decreased significantly (all p<0.001). Greater increases in LM-ht-Z were associated with infliximab therapy (p<0.05), increases in albumin (p<0.001), and decreases in ESR (p<0.05), interleukin-6 (p<0.005), and LBP (p<0.05). Greater increases in FM-ht-Z were associated with glucocorticoid, methotrexate, and infliximab therapy, and increases in albumin (p<0.05) and growth hormone binding protein (p<0.05). Overall, height-Z did not improve; however, greater increases in IGF-1 (p<0.05) and decreases in TNF-α (p<0.05), interleukin-6 (p<0.05) and LBP (p<0.05) levels were associated with increases in height-Z.
Immune-mediated mechanisms contribute to growth and body composition deficits in CD. Therapies should target these deficits.
Crohn’s disease; body composition; growth; nutrition; children
Objective To identify family-reported, adherence-related barriers for adolescents with inflammatory bowel disease (IBD) and examine their relationship to 6-MP/azathioprine and 5-ASA medication adherence. Methods Participants included 74 adolescents, aged 13–17 years, diagnosed with IBD and their caregivers. Adolescents and caregivers jointly completed a measure of barriers to medication adherence. Adherence to medication was measured by family-report, pill-count, and serum assay. Results Families endorsed one to seven total barriers to medication adherence. The most commonly reported barriers included forgetting, being away from home, and interference with an activity. Neither demographic nor disease severity variables were related to the total number of reported barriers. Fewer total reported barriers was related to better adherence by adolescent and maternal report. Conclusion Most families experience at least one barrier to treatment adherence. Effective problem-solving around these barriers and its integration into future treatment protocols may help improve medication adherence in the pediatric IBD population.
adherence; barriers; Crohn's disease; pediatric; ulcerative colitis
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.
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.
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.
Crohn disease; Ulcerative colitis; Well-being; Disease activity; Functional status
To examine prevalence and frequency of oral medication nonadherence using a multimethod assessment approach consisting of objective, subjective, and biological data in adolescents with IBD.
Medication adherence was assessed via pill counts, patient/parent interview, and 6-thioguanine nucleotide (6-TGN)/6-methylmercaptopurine nucleotide (6-MMPN) metabolite bioassay in 42 adolescents with inflammatory bowel disease. Pediatric gastroenterologists provided disease severity assessments.
Objective nonadherence prevalence was 64% for 6-MP/azathioprine and 88% for 5-ASA medications, whereas subjective nonadherence prevalence was 10% for 6-MP/azathioprine and 2% for 5-ASA. Objective nonadherence frequency was 38% for 6-MP/azathioprine and 49% for 5-ASA medications, and subjective nonadherence frequency was 6% for 6-MP/azathioprine and 3% for 5-ASA. Bioassay data revealed that only 14% of patients had therapeutic 6-TGN levels.
Results indicate that objectively measured medication nonadherence prevalence is consistent with that observed in other pediatric chronic illness populations, and that objective nonadherence frequency is considerable, with 40% to 50% of doses missed by patients. Subjective assessments appeared to overestimate adherence. Bioassay adherence data, while compromised by pharmacokinetic variation, might be useful as a cursory screener for nonadherence with follow up objective assessment. Nonadherence in one medication might also indicate nonadherence in other medications. Clinical implications and future research directions are provided.
Adherence; Compliance; Medication; Inflammatory Bowel Disease
We determined the impact of human growth hormone (GH) injections on growth velocity in growth impaired children with Crohn’s Disease (CD).
Ten children and adolescents (12.6±4.5 years; 6 male) with CD and poor height growth were treated with open label recombinant GH 0.043 mg/kg/day SQ for one 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 by DEXA scan.
Mean height velocity in GH-treated patients increased by 5.33±3.40 (mean ± SD) cm/yr during the year of GH compared with 0.96±3.52 cm/yr in the comparison group (p=0.03). Height Z score increased in the treated group by 0.76±0.38 compared with 0.16±0.40 in the comparison group (p<0.01), and weight Z score increased 0.81±0.89 compared with 0.00±0.57 (p<0.01). Bone density revealed an increase of the lumbar spine Z score by 0.31±0.33 (p=0.03 vs baseline).
GH treatment increases height velocity and potentially enhances bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is required to determine the ultimate impact of GH treatment.
DEXA; bone density; height; inflammatory bowel disease; osteoporosis
Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn’s disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 × 10−8 and 6.95 × 10−8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10−8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.
Objective To examine the relationship between medication adherence and quality of life (QOL) in adolescent patients with inflammatory bowel disease (IBD) utilizing a multimethod adherence assessment approach. Methods Medication adherence in 36 adolescents with IBD was assessed via interviews, pill counts, and biological assays. QOL was assessed via patient and parent report. Pediatric gastroenterologists provided disease severity assessments. Results Hierarchical multiple regression analyses revealed that adherence contributed significant variance to patient-reported QOL but not parent-reported QOL. Nonadherence to 6-MP/azathioprine was related to poorer patient-reported physical health QOL. Greater self-reported 5-ASA adherence was related to poorer overall psychological health QOL, and particularly social functioning QOL. Conclusions Results provide preliminary support for the negative effects of 6-MP/azathioprine nonadherence on QOL and an inverse relationship between 5-ASA adherence and QOL in this population. Adherence burden in patients and the utility of multimethod adherence assessment in research are discussed.
adherence; compliance; inflammatory bowel disease; quality of life
Childhood Crohn’s disease (CD) is associated with poor growth and decreased body mass index (BMI); however, lean mass (LM) and fat mass (FM) deficits prior to therapy have not been characterized.
To quantify LM and FM in incident pediatric CD subjects and controls, and to identify determinants of LM and FM deficits.
Whole body LM and FM were assessed using DXA in 78 CD subjects and 669 healthy controls, ages 5–21 yr. Gender specific z-scores for LM (LM-Ht) and FM (FM-Ht) relative to height were derived using log linear regression models in the controls. Multivariate linear regression models adjusted for potential confounders.
CD was associated with significantly lower height and BMI for age. Within CD subjects, FM-Ht and LM-Ht were significantly lower in females compared with males (FM-Ht z: −0.66 ± 0.83 vs. −0.08 ± 0.95, p < 0.01; LM-Ht z: −1.12 ± 1.12 vs. −0.57 ± 0.99, p < 0.05). In females, CD was associated with significantly lower LM-Ht (p < 0.001) and FM-Ht (p < 0.001), adjusted for age, race and Tanner stage, compared with controls. LM and FM deficits were significantly greater in older females with CD; 47% of adolescent females had LM-Ht ≤ 5th percentile. In non-black males, CD was also associated with lower LM-Ht (p < 0.02); FM-Ht deficits were not significant.
Incident CD was associated with significant LM deficits in males and females, and FM deficits in females. Future studies are needed to identify etiologies for the age and gender differences and to evaluate therapies for these deficits.
Inflammatory bowel disease; Crohn’s disease; growth failure; body composition; lean mass; fat mass; cachexia
Background & Aims
The impact of childhood Crohn’s disease (CD) on volumetric bone mineral density (vBMD), bone structure, and muscle mass have not been established. The objective of this longitudinal study was to assess musculoskeletal outcomes in an incident cohort of children with CD using peripheral quantitative computed tomography (pQCT).
Tibia pQCT was performed in 78 CD subjects (ages, 5–18 years) at diagnosis and in 67 over the subsequent year. pQCT outcomes were converted to sex- and race-specific z scores based on reference data in over 650 controls. Multivariable linear regression models identified factors associated with changes in bone outcomes.
At diagnosis, CD subjects had significant deficits in trabecular vBMD (z score, −1.32 ± 1.32; P < .001), cortical section modulus (a measure of bone geometry and strength) (z score, −0.44 ± 1.11; P < .01), and muscle (z score, −0.96 ± 1.02; P < .001) compared with controls. Over the first 6 months, trabecular vBMD and muscle z scores improved significantly (both, P < .001); however, section modulus worsened (P = .0001), and all 3 parameters remained low after 1 year. Increases in muscle z scores were associated with less severe declines in cortical section modulus z scores. Improvements in trabecular vBMD z scores were greater in prepubertal subjects. Glucocorticoids were associated with increases in cortical vBMD.
Substantial deficits in trabecular vBMD, cortical bone geometry, and muscle were observed at CD diagnosis. Trabecular vBMD improved incompletely; however, cortical deficits progressed despite improvements in muscle. Glucocorticoids were not associated with bone loss. Therapies to improve bone accrual in childhood CD are needed.