Immunosuppression Regimens for Intestinal Transplantation in Children.

Pediatric intestinal transplant serves as the only definitive treatment for children with irreversible intestinal failure. Successful intestinal transplant hinges upon appropriate management of immunosuppression. The indications for intestinal transplant have changed over time. Immunosuppression regimens can be divided into induction and maintenance phases along with treatment of acute rejection. Intestinal transplant induction now often includes antithymocyte globulin or basiliximab in addition to corticosteroids. Maintenance regimens continue to be dominated by tacrolimus, with additional agents used to either decrease goal tacrolimus levels to limit toxicity or as an adjunct in sensitized patients. Careful monitoring can help to limit serious complications, such as rejection, infection, and malignancy. Future work will aim to decrease variation in practice and identify methods to determine optimal immunosuppression for a particular patient. Furthermore, there is a need for non-invasive monitoring of the intestinal graft and functional assessments of immunosuppression.

Cost-effectiveness of ethanol lock prophylaxis to prevent central line-associated bloodstream infections in children with intestinal failure in the United States.

INTRODUCTION: Central line-associated bloodstream infections (CLABSIs) lead to significant morbidity and mortality in children with intestinal failure (IF). Ethanol lock prophylaxis (ELP) greatly reduces CLABSI frequency with minimal side effects. However, in the United States, a recently approved orphan drug designation for dehydrated alcohol has greatly increased 70% ethanol cost from about $10/day to $1000/day. We examined the cost-effectiveness of ELP in relation to these changes. METHODS: We simulated a previously developed IF Markov model over 1 year. Costs were measured in 2020 US dollars and effectiveness in quality-adjusted life-years (QALYs). CLABSI rate with and without ELP was estimated from the largest available comparative observational study. The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Secondary outcomes included CLABSI frequency. Sensitivity analyses on all model parameters were performed. RESULTS: In the base model, children with IF not using ELP accumulated $131,815 in costs and 0.32 QALYs per patient compared with $437,884 and 0.33 QALYs per patient in those using ELP. The ICER was nearly $17 million/QALY gained. ELP resulted in a 40% reduction in CLABSI frequency. ELP became cost-effective at $68/day and cost-saving at $63/day. Sensitivity analysis identified no other plausible parameter variation to reach the benchmark of $100,000/QALY gained. CONCLUSIONS: At the current price, ELP is not cost-effective for CLABSI prevention in children with IF in the United States. This study highlights the critical need for the approval of an affordable lock therapy option to prevent CLABSIs in these children.

Caregiver Decision-making in Pediatric Intestinal Failure: A Qualitative Study Focused on Iron Deficiency Anemia.

BACKGROUND: Caregivers of children with intestinal failure (IF) face difficult decisions without a clear best alternative. Providers assist in decision-making but often lack knowledge of caregiver perspectives. Using decision-making around anemia treatment as a focal point, we explored how caregivers of children with IF prefer to make decisions. Our goal was to offer insight to guide providers as they assist in decision-making. METHODS: We conducted 12 half-hour semistructured interviews with parents of children with IF. Interview questions addressed general decision-making and specifics of iron supplementation, including key factors and stakeholders in decision-making. Interviews were transcribed verbatim. Two investigators coded the transcripts and inductively derived themes. RESULTS: Four themes were identified regarding decision-making. They involved the search for reliable, accurate, and positive information; the role of caretakers on the medical team; the relationships between caretakers and the medical team; and effective communication. Themes around anemia treatment included: identification of anemia by bloodwork; proactive supplementation; individualized regimens; prioritizing safety and convenience. CONCLUSIONS: Understanding caregiver perspectives regarding anemia treatment in pediatric IF identifies opportunities for systematic quality improvement.

Microsimulation Model to Compare Enteral and Parenteral Iron Supplementation in Children With Intestinal Failure.

BACKGROUND: Children with chronic intestinal failure have a high prevalence of anemia, commonly from iron deficiency, leading to frequent blood transfusions. No current guideline exists for iron supplementation in these children. In this analysis, we evaluate the effectiveness and the cost-effectiveness of using parenteral, enteral, and no iron supplementation to reduce blood transfusions. METHODS: We created a microsimulation model of pediatric intestinal failure over a 1-year time horizon. Model outcomes included cost (US dollars), blood transfusions received, and hemoglobin trend. Strategies tested included no supplementation, daily enteral supplementation, and monthly parenteral supplementation. We estimated parameters for the model using an institutional cohort of 55 patients. Model parameters updated each 1-month cycle using 2 regressions. A multivariate mixed-effects linear regression estimated hemoglobin values at the next month based on data from the prior month. A mixed-effects logistic regression on hemoglobin predicted the probability of receiving a blood transfusion in a given month. RESULTS: Compared with no supplementation, both enteral and parenteral iron supplementation reduced blood transfusions required per patient by 0.3 and 0.5 transfusions per year, respectively. Enteral iron cost $34 per avoided blood transfusion. Parenteral iron cost an additional $6600 per avoided blood transfusion compared with enteral iron. CONCLUSIONS: We found both parenteral and enteral iron to be effective at reducing blood transfusions. The cost of enteral iron makes it the desired choice in patients who can tolerate it. Future work should aim to identify which subpopulations of patients may benefit most from one strategy over the other.

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: A Case Series With Long-term Follow-up and Prolonged Survival.

OBJECTIVES: Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients. METHODS: We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years. RESULTS: We identified 25 patients with MMIHS (68% girls, 13 transplanted). One transplanted and 1 nontransplanted patient were lost to follow-up. We estimated 100, 100, and 86% for 5-, 10-, and 20-year survival, respectively, with only 1 death. Of the 22 patients alive at the time of study (11 transplanted, 11 nontransplanted), median age was 9.2 years (range 2.7-22.9 years). Longest posttransplant follow-up was 16 years. Seventeen patients had available prenatal imaging reports; all showed distended bladder. Eight had genetic testing (5, ACTG2; 2, MYH11; 1, MYL9). Almost all patients had normal growth with median weight z-score -0.77 (interquartile range -1.39 to 0.26), height z score -1.2 (-2.04 to -0.48) and body mass index z-score 0.23 (-0.37 to 0.93) with no statistical difference between transplanted and nontransplanted patients. All nontransplanted patients were on parenteral nutrition with minimal/no feeds, and all except 1 of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin, and creatinine fell within the reference ranges. CONCLUSIONS: This is the largest single-center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis.

Cost-effectiveness of teduglutide in pediatric patients with short bowel syndrome: Markov modeling using traditional cost-effectiveness criteria.

BACKGROUND: Teduglutide use in pediatric patients with short bowel syndrome can aid in the achievement of enteral autonomy, but with a price of >$400,000 per y. OBJECTIVE: The current study evaluated the cost-effectiveness of using teduglutide in conjunction with offering intestinal transplantation in US pediatric patients with short bowel syndrome. DESIGN: A Markov model was used to evaluate the costs (in US dollars) and effectiveness [in quality-adjusted life years (QALYs)] of using teduglutide compared with offering intestinal transplantation. Parameters were estimated from published data where available. The primary effect modeled was the probability of weaning from parenteral nutrition while on teduglutide. Sensitivity analyses were performed on all model parameters. RESULTS: Compared with offering only intestinal transplantation, adding teduglutide cost ${\$}$124,353/QALY gained. Reducing the cost of the medication by 16% allowed the cost to reach the typical benchmark of ${\$}$100,000/QALY gained. Probabilistic sensitivity analysis favored transplantation without offering teduglutide in 68% of iterations at a ${\$}$100,000/QALY threshold. Never using teduglutide created an opportunity cost of over ${\$}$100,000 per patient. CONCLUSIONS: At its current price, teduglutide does not provide a cost-effective addition to transplantation in the treatment of pediatric short bowel syndrome. Further work should look to identify cost-reducing strategies, including alternative dosing regimens.

Should Children With Constipation Undergo Blood Lead Level Screening?

This study aimed to compare the prevalence of elevated blood lead level in children with constipation to the population prevalence. We reviewed the charts of 441 children who were screened with a blood lead level on presenting to the gastroenterology clinic at UPMC Children's Hospital of Pittsburgh for evaluation of constipation. The prevalence of blood lead level greater than 5 µg/dL was 1.36% (6/441; 95% confidence interval = 1.23% to 1.49%), which is significantly lower than the 4.01% prevalence in the population reported by the Center for Disease Control and Prevention. No patients had a blood lead level greater than 10 µg/dL. Age under 5 years old showed an increased odds of lead level greater than 5 µg/dL (odds ratio = 7.5; 95% confidence interval = 1.2 to 47.3, P < .05). We concluded that children seen in the gastroenterology clinic for constipation are unlikely to have an elevated blood lead level on routine screening.