Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials.

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.

Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group.

BACKGROUND: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.

Response to strict and liberalized specific carbohydrate diet in pediatric Crohn's disease.

AIM: To investigate the specific carbohydrate diet (SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease (CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple (diet alone, antibiotics or 5-ASA) or SCD with immunomodulators (corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics. RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years (range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo (range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization (P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

Out-of-pocket Cost Burden in Pediatric Inflammatory Bowel Disease: A Cross-sectional Cohort Analysis.

BACKGROUND: Pediatric inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), can result in significant morbidity requiring frequent health care utilization. Although it is known that the overall financial impact of pediatric IBD is significant, the direct out-of-pocket (OOP) cost burden on the parents of children with IBD has not been explored. We hypothesized that affected children with a more relapsing disease course and families in lower income strata, ineligible for need-based assistance programs, disparately absorb ongoing financial stress. METHODS: We completed a cross-sectional analysis among parents of children with IBD residing in California using an online HIPAA-secure Qualtrics survey. Multicenter recruitment occurred between December 4, 2013 and September 18, 2014 at the point-of-care from site investigators, informational flyers distributed at regional CCFA conferences, and social media campaigns equally targeting Northern, Central, and Southern California. IBD-, patient-, and family-specific information were collected from the parents of pediatric patients with IBD patients younger than 18 years of age at time of study, carry a confirmed diagnosis of CD or UC, reside in and receive pediatric gastroenterology care in California, and do not have other chronic diseases requiring ongoing medical care. RESULTS: We collected 150 unique surveys from parents of children with IBD (67 CD; 83 UC). The median patient age was 14 years for both CD and UC, with an overall 3.7 years (SD 2.8 yr) difference between survey completion and time of IBD diagnosis. Annually, 63.6%, 28.6%, and 5.3% of families had an OOP cost burden >$500, >$1000, and >5000, respectively. Approximately one-third (36.0%) of patients had emergency department (ED) visits over the past year, with 59.2% of these patients spending >$500 on emergency department copays, including 11.1% who spent >$5000. Although 43.3% contributed <$500 on procedure and test costs, 20.0% spent >$2000 in the past year. Families with household income between $50,000 and $100,000 had a statistically significant probability (80.6%) of higher annual OOP costs than families with lower income <$50,000 (20.0%; P < 0.0001) or higher income >$100,000 (64.6%; P < 0.05). Multivariate analysis revealed that clinical variables associated with uncontrolled IBD states correlated to higher OOP cost burden. Annual OOP costs were more likely to be >$500 among patients who had increased spending on procedures and tests (odds ratio [OR], 5.63; 95% confidence interval [CI], 2.73-11.63), prednisone course required over the past year (OR, 3.19; 95% CI, 1.02-9.92), at least 1 emergency department visit for IBD symptoms (OR, 2.84; 95% CI, 1.33-6.06), at least 4 or more outpatient primary medical doctor visits for IBD symptoms (OR, 2.82; 95% CI, 1.40-5.68), and history of 4 or more lifetime hospitalizations for acute IBD care (OR, 2.60; 95% CI, 1.13-5.96). CONCLUSIONS: Previously undocumented, a high proportion of pediatric IBD families incur substantial OOP cost burden. Patients who are frequently in relapsing and uncontrolled IBD states require more acute care services and sustain higher OOP cost burden. Lower middle income parents of children with IBD ineligible for need-based assistance may be particularly at risk for financial stress from OOP costs related to ongoing medical care.