Cisapride Use in Pediatric Patients With Intestinal Failure and Its Impact on Progression of Enteral Nutrition.

OBJECTIVE: Gastrointestinal dysmotility is common in patients with pediatric intestinal failure (PIF), leading to delays in advancement of enteral nutrition (EN). Few studies have been published regarding the safety and efficacy of cisapride for improvement of enteral tolerance and ability to wean parenteral nutrition. Our objective was to describe a single center experience on the use of cisapride in patients with PIF. METHODS: Retrospective chart review of patients was performed. Demographic, intestinal anatomy, and outcome data were collected. Percentage of EN before initiation of cisapride, progression of EN at 3 and 6 months, and ability to wean parenteral nutrition after initiation of cisapride were calculated. RESULTS: Prokinetics were used in 61 of 106 patients (56.6%); 29 of 60 patients (48.3%) failed to progress EN on other prokinetics and started on cisapride. Before cisapride the progress of EN plateaued for a mean of 42.3 (standard deviation [SD] 60.2) days. The rate of feed progression was 0.14% (SD 0.19)/day pre-cisapride and 0.69%/day (SD 0.31) after cisapride initiation (P < 0.001). Percentage of EN improved significantly from baseline to 3 months postinitiation (23.9% vs 79.4%, respectively; P < 0.001). Electrocardiogram was performed on initiation of cisapride and after every dose change. Medication was discontinued in 2 of 29 (6.8%). CONCLUSION: This retrospective study suggests that cisapride may be beneficial in PIF patients who fail to progress EN on first line prokinetics. The most significant period of improvement occurs within 3 months of cisapride initiation. Cardiac side effects in our cohort were lower than previously reported; however, cardiac monitoring is still recommended.

Neurocognitive Functioning in Early School-age Children With Intestinal Failure.

OBJECTIVES: Little is known about school-age functioning in children with intestinal failure (IF). This study examines neurocognitive outcomes of children with IF at ages 4 to 8 years treated at a single centre, along with relevant medical and demographic variables. METHODS: Between 2012 and 2016, neurocognitive assessments were administered to 28 children receiving treatment in our IF rehabilitation program, and included measures of intelligence, academics, learning/memory, language, visual-motor integration, and fine-motor dexterity. DSM-IV/V criteria were used to diagnose Learning Disability, Intellectual Disability, and/or Attention Deficit/Hyperactivity Disorder. RESULTS: Intellectual functioning ranged from extremely low to superior (Full Scale IQ range 53-123, mean = 89). Forty-six percentage received a cognitive/learning DSM diagnosis. Total number of first-year septic episodes correlated with poorer outcomes on the most cognitive measures. Adjusting for gestational age (61% were born <37 weeks), number of first-year septic episodes negatively predicted working memory, visual-motor integration, and visual memory scores. Additional factors correlating with poorer outcomes on ≥2 cognitive measures included length of first-year admissions, necrotizing enterocolitis diagnosis, and first-year sustained conjugated hyperbilirubinemia. Having ≥2 first-year septic episodes increased the likelihood of poorer outcome. Having a sibling was a significant positive predictor of working memory, processing speed, reading, and verbal learning skills. CONCLUSIONS: Our data provides preliminary evidence that children with IF are at risk of neurocognitive problems at early school age. Managing septic events during the first year is one strategy that may help reduce long-term neurocognitive risks in this population.

Health-related quality of life in neonates and infants: a conceptual framework.

PURPOSE: With reduced mortality of neonatal conditions, health-related quality of life (HRQOL) has become an important clinical outcome. However, since the meaning of HRQOL in dependent, non-autonomous infants and neonates remains largely undefined, HRQOL measurement and economic evaluation are limited due to the lack of age-specific methodology. The objective was to construct a conceptual framework of neonatal and infant HRQOL (NIHRQOL) which identifies factors relevant to the neonate and infant, their relationship with each other and the caregiving environment. METHODS: Using qualitative methods, a concept was developed based on in-depth analysis of verbatim records of two focus groups (6 caregivers, 6 healthcare providers) and five interviews with caregivers of chronically ill neonates/infants (n = 2), and healthcare professionals of a pediatric tertiary healthcare center (n = 3). Two analysts independently performed thematic analysis using an inductive and contextual approach. RESULTS: The majority of participants regarded NIHRQOL as an individual entity, which was closely related and strongly influenced by caregivers and family. It may be gauged by the perceived degree of effort required to achieve expected normalcy in everyday life for the neonate/infant and its family. The importance of individual HRQOL factors is developmental stage-dependent. CONCLUSION: Neonatal and infant HRQOL is a multidimensional, multilayered and interconnected concept, where the child's needs contribute most directly, and the caregiver's and society's ability to meet those needs characterize the interdependence between the child and its caregiving environment. Developmental stage-specific HRQOL instruments for premature and mature neonates, and infants are warranted to allow for valid HRQOL measurement.

Predicting Intestinal Adaptation in Pediatric Intestinal Failure: A Retrospective Cohort Study.

OBJECTIVE: The primary goal in intestinal failure (IF) is adaptation and enteral autonomy (EA). Our goals were to determine the proportion of patients treated for IF by an established intestinal rehabilitation program who achieved EA and to assess the predictors of EA. BACKGROUND: There have been considerable advancements in the management of IF over the last 15 years, children with short bowel syndrome with a reduction in mortality. Several studies have discussed variables that may influence the ability to attain EA; however, majority were written when mortality rates were considerably higher compared with the current contemporary experience. METHODS: A retrospective analysis of infants <12 months with short bowel syndrome referred between 2006 and 2013 (n = 120). Data was collected on IF-related factors and nutritional intake. The cohort was stratified based on achievement of EA. Statistical testing completed using t test, Chi Square, and Cox Proportional Hazards regression (P < 0.05). RESULTS: EA was achieved in 84 (70.0%) patients. Patients who remained parenteral nutrition dependent were more likely to have volvulus (1.2 vs 22.2%, P < 0.001), shorter percent residual small bowel (29.4 vs 68.6%; P < 0.0001) and colon length (64.6 vs 86.0%; P = 0.001), and no ileocecal valve (61.1 vs 29.8%; P = 0.05). Mortality was also decreased in those who achieved EA (4 vs 22%; P = 0.004). Percent residual small bowel (HR = 1.03; 95% CI 1.02-1.03) and colon (HR = 1.01; 95% CI 1.00-1.02) length were positively associated with EA, while number of septic episodes was negatively associated (HR = 0.95; 95% CI 0.91-0.99). CONCLUSION: Seventy percent of infants with IF achieved EA. Residual small and large bowel length were the most important predictors of EA and septic events had a negative impact.

Impact of Intestinal Rehabilitation Program and Its Innovative Therapies on the Outcome of Intestinal Transplant Candidates.

OBJECTIVES: The outcome of children with intestinal failure has improved during the past decade following the introduction of novel therapies by dedicated intestinal rehabilitation programs (IRP). The aim of the present study was to assess the impact of IRP on the outcome of intestinal transplant (IT) candidates and the transplant waiting list. METHODS: A retrospective cohort study of children assessed for IT (n = 84) during a 10-year period. Comparisons were made among the following 3 time periods: before the establishment of our center's IRP (1999-2002; n = 33), early IRP (2003-2005; n = 18), and late IRP (2006-2009; n = 33). The following endpoints were used: patient outcome following IT assessment (not listed, listed and removed from the list, received transplant, died while on the list), patient characteristics at IT assessment, and patient status at the end of the study. RESULTS: The late-IRP era was associated with an increase in patients who were not listed (42% vs 28% at other periods, P = NS) and patients who were removed from the IT waiting list because of clinical improvement (P < 0.0005), and a decrease in those who died before transplant (15% vs >60% at other periods, P < 0.0005). The cause of death shifted from traditional causes such as liver failure or sepsis to other comorbid conditions (P < 0.005). Improved liver function at listing was also observed during late IRP (P < 0.005). CONCLUSIONS: Treatment by IRP, coupled with recent advances in the medical management of intestinal failure, is associated with improved survival and outcome of patients waiting for IT, and may lead to overall reduction in the number of IT in the future.

Hidden figures: how legal experts influence the design of international institutions.

Whose preferences influence the design of international institutions? Scholarship on the legalization of international politics and creation of international legal institutions largely adopts a state-centric perspective. Existing accounts, however, fail to recognize how states often delegate authority over institutional design tasks to independent legal experts whose preferences may diverge from those of states. We develop a principal-agent (PA) framework for theorizing relations between states (collective principals) and legal actors (agents) in the design process, and for explaining how legal actors influence the design of international institutions. The legal dimensions of the PA relationship increase the likelihood of preference divergence between the collective principal and the agent, but also create conditions that enable the agent to opportunistically advance its own design preferences. We argue that the more information on states' preferences the agent has, the more effectively it can exploit its legal expertise to strategically select and justify design choices that maximize its own preferences and the likelihood of states' acceptance. Our analysis of two cases of delegated institutional design concerning international criminal law at the United Nations and the African Union supports our theoretical expectations. Extensive archival and interview data elucidate how agents' variable information on states' preferences affects their ability to effectively advance their design preferences. Our theory reveals how independent legal experts with delegated authority over design tasks influence institutional design processes and outcomes, which has practical and normative implications for the legalization of international politics.

Enhanced Recovery After Surgery (ERAS) Society Recommendations for Neonatal Perioperative Care.

Importance: Neonates requiring surgery are often cared for in neonatal intensive care units (NICUs). Despite a breadth of surgical pathology, neonates share many perioperative priorities that allow for the development of unit-wide evidence-based Enhanced Recovery After Surgery (ERAS) recommendations. Observations: The guideline development committee included pediatric surgeons, anesthesiologists, neonatal nurses, and neonatologists in addition to ERAS content and methodology experts. The patient population was defined as neonates (first 28 days of life) undergoing a major noncardiac surgical intervention while admitted to a NICU. After the first round of a modified Delphi technique, 42 topics for potential inclusion were developed. There was consensus to develop a search strategy and working group for 21 topic areas. A total of 5763 abstracts were screened, of which 98 full-text articles, ranging from low to high quality, were included. A total of 16 recommendations in 11 topic areas were developed with a separate working group commissioned for analgesia-related recommendations. Topics included team communication, preoperative fasting, temperature regulation, antibiotic prophylaxis, surgical site skin preparation, perioperative ventilation, fluid management, perioperative glucose control, transfusion thresholds, enteral feeds, and parental care encouragement. Although clinically relevant, there were insufficient data to develop recommendations concerning the use of nasogastric tubes, Foley catheters, and central lines. Conclusions and Relevance: Despite varied pathology, neonatal perioperative care within NICUs allows for unit-based ERAS recommendations independent of the planned surgical procedure. The 16 recommendations within this ERAS guideline are intended to be implemented within NICUs to benefit all surgical neonates.

Peripherally inserted central catheters for long-term parenteral nutrition in infants with intestinal failure.

BACKGROUND AND AIM: Infants with intestinal failure often require long-term central access for delivery of parenteral nutrition (PN). Traditionally, surgically placed central venous catheters (CVCs) have been used; however, the complications associated with these catheters can lead to significant morbidity. Peripherally inserted central catheters (PICCs) are potentially superior to CVCs because they tend to be smaller, and can be placed without general anesthesia. The purpose of the study is to report the use of PICCs for long-term administration of PN in infants with intestinal failure and compare with previously published catheter infection and venous thrombosis rates. METHODS: A 4-year review of infants younger than 12 months with intestinal failure and a PICC for PN delivery was performed to determine the incidence of catheter-related bloodstream infections (CRBSIs) and PICC-associated venous thrombosis. The complication rates were compared with those reported for CVCs and PICCs in the pediatric literature. RESULTS: A total of 45 infants with intestinal failure, receiving PN through a PICC were included in the study. Data from 95 PICCs accounting for 10,189 catheter days were collected. The overall incidence of CRBSI was 5.3/1000 catheter days and the incidence of venous thrombosis was 2.0/1000 catheter days. CONCLUSIONS: PICCs offer an advantage over CVCs in that they can often be inserted without a general anesthesia and do not require manipulation of the vein. Given the low rate of CRBSI and venous thrombosis, we recommend PICCs for infants with intestinal failure requiring PN.

Human growth hormone and glutamine for patients with short bowel syndrome.

BACKGROUND: There has been clinical enthusiasm for treating short bowel patients with human recombinant growth hormone and/or glutamine in hopes of reducing parenteral nutrition dependency. It has been more than a decade since Byrne and colleagues reported enhanced absorption of nutrients, improved weight gain, and reduction in parenteral nutrition requirements with the administration of a combination of human growth hormone (HGH) and glutamine in patients with short bowel syndrome. Other studies have reported inconsistent results. OBJECTIVES: The purpose of this systematic review was to evaluate the efficacy of growth hormone with or without glutamine supplementation for adult patients with short bowel syndrome. SEARCH STRATEGY: Electronic searches were performed to identify all publications describing randomised controlled trials of the use of human growth hormone with or without glutamine for the treatment of patients with short bowel syndrome. SELECTION CRITERIA: Randomised controlled trials of human growth hormone with or without glutamine for patients with short bowel syndrome were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the published studies. The statistical analyses were performed using RevMan 5 software. Follmann's method was used for cross-over studies. MAIN RESULTS: Five studies were included in the review. Human growth hormone with or without glutamine appears to provide benefit in terms of increased weight (MD 1.66 Kg; 95% CI 0.69 to 2.63;P = 0.0008), lean body mass (MD 1.93 Kg; 95% CI 0.97 to 2.90; P = 0.0001) energy absorption (MD 4.42 Kcal; 95% CI 0.26 to 8.58; P = 0.04) and nitrogen absorption (MD 44.85 g; 95%CI 0.20 to 9.49; P = 0.04) for patients with short bowel syndrome. The single RCT that focused on parenteral nutrition (PN) requirements demonstrated decreased PN volume and calories and number of infusions in patients who received HGH with or without glutamine supplementation. Only patients who received HGH with glutamine maintained statistically significant PN reductions at 3 month follow-up. AUTHORS' CONCLUSIONS: The results suggest a positive effect of human growth hormone on weight gain and energy absorption. However, in the majority of trials, the effects are short-lived returning to baseline shortly after cessation of therapy. The temporary benefit calls into question the clinical utility of this treatment. To date, the evidence is inconclusive to recommend this therapy. Consideration should be made to studying patients during the active phase of intestinal adaptation rather than in the setting of chronic intestinal failure. The role of HGH in paediatric short bowel syndrome remains unknown.

Content validity of a process evaluation checklist to measure intervention implementation fidelity of the EPIC intervention.

BACKGROUND: The Evidence-Based Practice Identification and Change (EPIC) intervention is a complex multifaceted knowledge translation strategy that combines the use of evidence and continuous quality improvement to change health care professional practices. However, there is no measure to evaluate the fidelity (degree to which the intervention was implemented as planned) of the EPIC intervention. AIM: To examine the content validity of the Process Evaluation Checklist (PEC), a newly developed measure to assess the fidelity of the EPIC intervention. METHODS: Eight health care professionals with experience in the delivery of the EPIC intervention rated the importance/relevance of items in assessing the scale/subscales of the PEC. A content validity index was computed for each item (I-CVI) and for each scale/subscale (S-CVI) in the measure. RESULTS: I-CVIs ranged from 0.6 to 1.0 and S-CVIs ranged from 0.3 to 1.0. Two items were eliminated, while nine items were retained. CONCLUSIONS: Content validity of the PEC was established. The PEC will be used to evaluate the implementation fidelity of the EPIC intervention in future trials.

Factors Related to the Development of Small-Bowel Bacterial Overgrowth in Pediatric Intestinal Failure: A Retrospective Cohort Study.

BACKGROUND: Small bowel bacterial overgrowth (SBBO) is a challenge in the management of pediatric intestinal failure (PIF). Our goal was to determine the proportion of patients treated for SBBO and factors related to its development. METHODS: We completed a retrospective analysis of PIF patients referred between 2008 and 2014. Data were collected on factors related to intestinal failure (IF) and SBBO. The cohort was stratified on the diagnosis of SBBO and refractory SBBO. Statistical testing completed using t-test, χ2 test, and logistic regression. RESULTS: Thirty-five of 102 patients developed SBBO (34%), and 16 (16%) had refractory SBBO. SBBO was more likely in gastroschisis (40.0% vs 19.4%, P = .025), a shorter residual small bowel (SB) (45.4% vs 66.5%, P = .004), and patients were less likely to wean from parenteral nutrition (PN) (51.4% vs 85.1%, P < .0001). Refractory SBBO patients were likely to have gastroschisis (50.0% vs 22.1%, P = .020) and a shorter residual SB and large bowel remaining (23.2% vs 65.9%, P < .0001 and 60.6% vs 79.4%, P = .03, respectively) and less likely to wean from PN (37.5% vs 80.2%, P = .001). Logistic regression demonstrated that longer SB residual was protective (P = .001; odds ratio [OR], 0.95; 95% CI, 0.93-0.99), and short bowel syndrome (SBS) as a cause of IF was a risk factor (P = .001; OR, 0.04; 95% CI, 0.01-0.27). CONCLUSION: A longer SB remnant was protective against SBBO. Patients with SBBO were more likely to have PIF caused by SBS.

An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure-Associated Liver Disease in Infants With Intestinal Failure.

BACKGROUND: SMOFlipid has a more diverse lipid profile than traditional Intralipid and has become the standard lipid for patients in our intestinal rehabilitation program. Our objective was to compare outcomes in neonates with intestinal failure (IF) who received SMOFlipid against those receiving Intralipid. METHODS: This was a retrospective cohort study of infants with IF with a minimum follow-up of 12 months in 2008-2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels. Statistical analysis included the Mann-Whitney U and χ2 tests, with an α value < 0.05 considered significant. Approval was obtained from our institutional review board. RESULTS: Thirty-seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z-scores were improved for patients receiving SMOFlipid at 3 months (-0.932 vs -2.092; P = 0.028) and 6 months (-0.633 vs -1.614; P = 0.018). There were no differences in PN-supported patients or demographics between the groups. CONCLUSION: Use of SMOFlipid resulted in decreased development of IF-associated liver disease in patients with IF when assessed using biochemical tests.

The evolution of the serial transverse enteroplasty for pediatric short bowel syndrome at a single institution.

PURPOSE: The serial transverse enteroplasty (STEP) tapers and lengthens the gut to improve adaptation. Mortality has decreased with multidisciplinary intestinal rehabilitation programs (IRP) allowing more time to reach adaptive potential. We reviewed our STEP experience to compare surgical outcomes between early and late eras of our IRP. METHODS: A retrospective cohort study of all STEP patients managed by our IRP (Jan 2003-Dec 2016; era 1 2003-2005, era 2 2006-2016) was completed. Patient demographics, operative data, complications, and outcome data were collected. Univariate analysis between eras with nonparametric statistics was performed. RESULTS: Thirty-six patients received STEP (Era 1 = 12; Era 2 = 24) [median age 5mo; males 22/36 (61.1%)]. In Era 2 a higher proportion had gastroschisis (8.3% vs 58.3%); p = 0.004) and shorter pre-STEP small bowel remnant (48 vs 111 cm, p = 0.001). The median increase in bowel length post-STEP was 52.9%. Overall, 42% of patients reached enteral autonomy (Era 1 7/12 (58%) vs Era 2 8/24 (33%); p = 0.15). Median time to PN discontinuation was shorter in Era 1 (259 vs 968 days, p = .208). Staple line complications were higher in Era 1 (16.7% vs 0%; p = 0.040). CONCLUSION: Presently, STEP is reserved for a specific subset of IRP patients, allowing 42% to wean off PN. STEP's use should be under the umbrella of a multidisciplinary IRP. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Early Predictors of Enteral Autonomy in Pediatric Intestinal Failure Resulting From Short Bowel Syndrome: Development of a Disease Severity Scoring Tool.

INTRODUCTION: Patients with short bowel syndrome (SBS) are dependent on parenteral nutrition (PN) while their bowel attempts to compensate. Our objective was to create an SBS disease severity score to predict the probability of achieving enteral autonomy (EA). METHODS: A retrospective cohort study of children with SBS managed by our Intestinal Rehabilitation Program was completed. Data abstracted included demographic, bowel anatomy, and outcome variables including conjugated bilirubin (CB) and enteral nutrition (EN) tolerated 6 months postoperatively. Univariate analysis and Cox proportional hazards (CPH) model were performed. A score was created based on weighting of coefficients. An α-value of < 0.05 was considered significant. RESULTS: One hundred thirty-nine patients were analyzed (61% males). Ninety-five (68%) achieved EA. Patients possessing >50% residual small bowel (hazard ratio [HR] 2.68 [95% confidence interval {CI} 1.60-4.49], P < 0.001), ileocecal valve intact (HR 0.61 [95% CI 0.37-1.01], P < 0.055), and >50% enteral tolerance at 6 months (HR 5.70 [95% CI 2.77-11.74] P < 0.001) were positively associated with EA. CB >34 µmol/L (2 mg/dL) was negatively associated with EA (HR 0.42 [95% CI0.27-0.66], P < 0.001). A severity score was created by weighting CPH parameter estimates (small bowel length >50%, ileocecal valve intact, CB <34 µmol/L, and EN >50% for a maximum score of 8), and disease severity strata were developed (severe [25.7% EA], moderate [52.9% EA], and mild [97.1% EA]). CONCLUSION: We propose a pediatric SBS disease severity score that predicts probability of EA. The score allows prognostication of individual patients and could assist research by adjusting outcome reporting or stratifying recruitment.

Neurodevelopmental outcomes of infants with intestinal failure at 12 and 26 months corrected age.

BACKGROUND: Survival rates of infants with intestinal failure (IF) are increasing, yet multiple medical factors may impact development. AIMS: This study examines neurodevelopmental outcomes at 12-15 and 26-32 months corrected age in a cohort of children with IF. STUDY DESIGN: Prospective single centre neurodevelopmental assessments of children admitted to an intestinal rehabilitation program between 2011 and 2013. Outcome measures include: Mullen Scales of Early Learning (12 and 26 months), and Vineland-II Adaptive Behaviour Scales - Caregiver Report (26 months). Standard scores were correlated with medical and demographic factors. RESULTS: Thirty-one children (17 males), median gestational age 34 weeks (IQR 30-36) with birth weight (BW) 2.12 kg (IQR 1.24-2.52). Ten (32.2%) were dependent on parental nutrition (PN) at the second assessment. At 12 months, 11/30 (36.7%) scored below average (>1SD below mean) on the early learning composite and 24/30 (80%) were below average on the gross motor subscale. Comparatively, at 26 months, mean early learning scores were significantly lower with >50% scoring below average. Mean gross motor scores remained low, and 14/27 (51.9%) were below average on the Vineland-II motor domain. At 12 months, factors significantly associated with lower scores are primarily related to prematurity. At 26 months, the impact of IF-related variables such as bowel length and PN days are more apparent. CONCLUSION: Children with IF are at risk of developmental delay in multiple domains. While gross motor skills appear to be most significantly affected, cognitive deficits become more apparent at 26 months, highlighting the importance of early developmental follow up.

Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion.

BACKGROUND: Pediatric intestinal failure (PIF) is a life-altering chronic condition with significant morbidity and mortality. Omegaven® therapy has been used to treat children with advanced intestinal failure associated liver disease. Our objective was to determine the evolution of hepatic fibrosis in PIF patients who received Omegaven® and describe their clinical outcome. METHODS: A retrospective review in PIF patients who received Omegaven® was performed. Patients were included if they had liver biopsies completed before Omegaven® therapy and after resolution of hyperbilirubinemia. Biopsy results were evaluated to determine the degree of fibrosis, inflammation, and cholestasis. Clinical and biochemical data was collected. RESULTS: Six patients were identified. Assessment of fibrosis at last follow-up demonstrated improvement in 2 patients and progression or stable fibrosis in 4/6. All patients demonstrated reduction in cholestasis and inflammation. One patient received a liver/intestine transplant and a second is listed, both of them with progressive fibrosis. One patient achieved full enteral nutrition, while the rest remain partially parenteral nutrition dependent. CONCLUSION: Use of Omegaven® is associated with reduced cholestasis and inflammation, but with persistence or worsening of fibrosis in some patients. A subset of patients with progressive fibrosis may develop portal hypertension and progressive liver disease.

Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid.

BACKGROUND: To examine whether SMOFlipid prevents progression of intestinal failure-associated liver disease (IFALD) in parenteral nutrition (PN)-dependent infants with early IFALD (conjugated bilirubin 17-50 µmol/L, 1-3 mg/dL). STUDY DESIGN: Pilot multicenter blinded randomized controlled trial comparing SMOFlipid with Intralipid. Patients received the trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin. RESULTS: Twenty-four infants (mean age, 6 weeks) participated in the trial (13 Intralipid and 11 SMOFlipid). At the time of trial enrollment, patients in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks and did not differ according to treatment ( P = .99). At trial conclusion, patients who received SMOFlipid had a lower conjugated bilirubin than those who received Intralipid (mean difference, -59 µmol/L; P = .03). Patients receiving SMOFlipid were also more likely to have a decrease in serum conjugated bilirubin to 0 µmol/L than those in the Intralipid group over the entire observation period (hazard ratio, 10.6; 95%; P = .03). The time to achievement of full enteral tolerance did not differ statistically (hazard ratio, 1.3; P = .59) between the groups. There was no significant difference in safety outcomes between the groups. CONCLUSIONS: Compared with Intralipid, SMOFlipid reduces the risk of progressive IFALD in children with intestinal failure. This trial was registered at clinicaltrials.gov as NCT00793195.

Cost of ambulatory care for the pediatric intestinal failure patient: One-year follow-up after primary discharge.

BACKGROUND: Survival of children with intestinal failure has improved over the last decade, resulting in increased health care expenditures. Our objective was to determine outpatient costs for the first year after primary discharge. METHODS: A retrospective analysis was performed in pediatric intestinal failure (PIF) patients between 2010 and 2012. Patients were stratified into 3 groups (1=enteral support with no devices [7 patients], 2=enteral support with devices (gastrostomy and/or ostomy) [19 patients], 3=home parenteral nutrition (HPN) [22 patients]). Data abstraction included clinical characteristics and costs related to medication, enteral/parenteral nutrition, and supplies were calculated. Data were analyzed using one way ANOVA. RESULTS: Forty-eight patients (mean age 7.6months; 31 males [65%]) were studied. See attached table for results. HPN patients had significantly more ambulatory visits (p<0.0001), number of admitted days (p=0.01), and productive days lost (p<0.0001). Total cost of care was significantly higher for HPN patients (mean=$320,368.50, p<0.0001) when compared to other groups. Costs covered by the health care system were significantly higher for patients on HPN (mean=$316,101.56, p<0.0001). CONCLUSION: The outpatient expenditures to care for PIF patients in the first year post primary discharge are significant. Our single payer health care system supports the majority of costs, but families are also incurring expenses related to travel and lost productivity. Children on HPN have more visits to hospital, but have access to more funding options. Children solely on gastrostomy or stoma therapy, however, have a significantly greater personal financial burden.

Change of Outcomes in Pediatric Intestinal Failure: Use of Time-Series Analysis to Assess the Evolution of an Intestinal Rehabilitation Program.

BACKGROUND: The clinical picture of pediatric intestinal failure has changed over the past 15 years, while effectiveness evolving treatment options remains unclear. This study explored evolution in care and quantified independent effects of new treatment options. STUDY DESIGN: Consecutive patients (n = 196) with neonatal or infantile intestinal failure, born between July 1996 and December 2011, were derived from an intestinal rehabilitation program (IRP) patient registry. Change over time was analyzed using multivariable Box-Jenkins method-based autoregressive integrative moving average models (ARIMA), robust linear regression, and nonparametric trend analysis. Four systematically introduced treatment options (IRP, serial transverse enteroplasty, omega-3 lipid emulsions, and ethanol locks) were evaluated. Analyses were adjusted for patient characteristics and disease severity. The primary outcome was disease-specific mortality from liver failure and sepsis. Secondary outcomes included parenteral nutrition weaning, transplantations, catheter complications, and liver disease. RESULTS: Patient characteristics remained unchanged over time, except for decreasing small bowel length (-0.5%/quarter; 95% CI -0.85, -0.16) and ICU admission time (-0.6 days/quarter; 95% CI -1.03, -0.18). Disease-specific mortality diminished significantly over time (-0.02 deaths/quarter; 95% CI -0.03, -0.01) by IRP and omega-3 lipids introduction (-0.6 deaths/quarter each, 95% CI -1.23, -0.02 and -0.77, -0.45, respectively). Serial transverse enteroplasty and ethanol locks had no significant impact. Parenteral nutrition weaning and transplantations remained unchanged, while catheter sepsis and complication rates decreased by 0.3 episodes/1,000 catheter-days each (95% CI -0.43, -0.2 and -0.45, -0.24, respectively). CONCLUSIONS: Introduction of IRP and omega-3 lipids independently decreased disease-specific mortality. For the first time, time series analysis was applied to evaluate effectiveness of treatment options in intestinal rehabilitation.

Prevalence of renal abnormality in pediatric intestinal failure.

BACKGROUND: Outcomes of children with intestinal failure have improved over the last decade. However, with improved survival, other co-morbidities have become evident. The goal of our study was to evaluate the presence of renal nephrocalcinosis or increased echogenicity in a cohort of patients with pediatric intestinal failure (PIF). METHODS: A cross-sectional prevalence design was performed in PIF patients followed by our intestinal rehabilitation program between 2013 and 2014. Renal function was evaluated using serum creatinine and urea, urine oxalate, creatinine, calcium, and calcium/creatinine ratios. Renal ultrasounds were performed to assess for echogenicity. Data was collected on intestinal failure related factors and nutritional intake. Data was analyzed using medians and Mann-Whitney U or proportions and chi square. RESULTS: Fifty-four patients (median age 48months; 33 males (61%) were studied. Twenty-two patients (41%) had increased echogenicity or nephrocalcinosis on ultrasound. There were no differences in serum Creatinine or urea, but patients with nephrocalcinosis had statistically different calcium:creatinine ratio (1.69 vs 0.74; p=0.043), urine oxalate (108 vs 219; p=0.06), and serum phosphate (1.55 vs 1.75; p=0.044). Patients with echogenicity had a shorter colonic remnant (25cm vs 31cm; p=0.01), a history of longer PN exposure (928 vs 483days; p=0.05), percent PN calories (37 vs 0; p=0.05), PN h/day (13 vs 0; p=0.05), but no difference in PN Ca/phosphate/magnesium content (mmol/kg). CONCLUSION: A large proportion of PIF patients have increased echogenicity/nephrocalcinosis on ultrasound that is associated with prolonged PN exposure. This has implications for long-term management. Regular surveillance is required, and further study is warranted to determine specific risk factors.