Changes over time in self-efficacy and the allocation of responsibility for health management tasks in pediatric liver transplant recipients: Targets to improve the transition process.

BACKGROUND: The process of transition to adult-based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long-term outcome. METHODS: This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic. We investigated changes in these constructs over time. We further investigated the relationship between the change in these constructs over time spent in a focused transition program with adherence. RESULTS: The primary component underlying our transition readiness survey for patients and parents represented self-efficacy. Time spent in the transition program was an independent predictor of change in self-efficacy (rho 0.299, p = .015); however, the magnitude of that change had no relationship to adherence. Change in parent-proxy self-efficacy was found to have a statistically significant relationship with tacrolimus standard deviation (rho -0.301, p = .026). There was disagreement identified between patient and parent responses on the survey. Neither change in patient nor parent reports of self-efficacy was found to have a relationship with post-transfer adherence. CONCLUSIONS: This study reaches the novel conclusion that self-efficacy and parent-proxy self-efficacy are dynamic concepts that change over time spent in a focused transition program. The patient-parent disagreement and the relationship between parent-proxy self-efficacy and adherence stress the importance of involving parents/guardians in the transition process as well.

Clinical Features and Biomarkers Suggestive of Bloodstream Infection in Pediatric Patients With Intestinal Failure and Central Venous Lines for Parenteral Nutrition: A Retrospective Pilot Study.

OBJECTIVES: This study aimed to describe demographic, clinical, and laboratory values in febrile pediatric intestinal failure patients with indwelling central venous catheters presenting to the emergency department to determine if there are low-risk features predictive of negative blood cultures that could help identify a subset that do not need hospitalization and/or broad-spectrum antibiotics. METHODS: We conducted a retrospective cohort study of febrile patients younger than 18 years with diagnosis of intestinal failure requiring a central venous catheter for home parenteral nutrition to identify factors associated with normal blood cultures to identify a low-risk subset. RESULTS: Of 119 encounters, 46% had a bloodstream infection. Children with a bloodstream infection were older than those without. A normal lactate and heart rate were associated with negative blood cultures. CONCLUSION: Pediatric intestinal failure patients with a central venous catheter for home parenteral nutrition presenting to the emergency department with fever and found to have a normal lactate and heart rates had lower rates of bloodstream infection. Although we were unable to create a highly sensitive clinical decision-making rule to identify a low-risk cohort because of the low number of patients meeting both criteria, the promising candidate variables identified merit for future multicenter studies.

Morphometric Changes in Children With Small Bowel Crohn Disease During Induction of Therapy: A Pilot Study.

OBJECTIVE: Children and adolescents with Crohn disease (CD) commonly gain weight during treatment induction, which is thought to be a marker of better health. Body composition is, however, rarely assessed at diagnosis, and changes during early treatment are not often quantified. Therefore, it is unknown if these gains are truly healthy. We sought to evaluate skeletal muscle changes during initial treatment for CD by using routine imaging. METHODS: Single-center prospective study. Pediatric patients diagnosed with small bowel CD underwent serial magnetic resonance enterography (MRE) imaging, laboratory testing, and disease-activity assessment, at diagnosis, 1 and 6 months of treatment. MRE-based cross-sectional morphometry was used to measure psoas muscle cross sectional area (CSA). Psoas CSA z-scores were calculated using normative data. RESULTS: We enrolled 30 children (ages 9--17 years). Twenty-eight of 30 (93%) received anti-tumor necrosis factor therapy and 4 required surgical resection. Children with below-average psoas CSA and body mass index (BMI) z-scores at diagnosis were much more likely to fail treatment or undergo surgery by 6 months compared with those with higher z-scores (55% vs 0%; P = 0.001). Children with no activity limitations at diagnosis had significantly larger muscle gains in the first month, compared with those whose activity was limited at diagnosis (P = 0.012). Most patients had higher psoas CSA z-scores by 6 months, and these increases were associated with weight and BMI z-score increases. CONCLUSIONS: Skeletal muscle growth contributes to weight gain during treatment induction in most patients with CD. Psoas muscle CSA on diagnostic imaging may have prognostic value in children with CD.

Health literacy and its association with adherence in pediatric liver transplant recipients and their parents.

OBJECTIVE: Non-adherence to pediatric regimens is a common concern. Low health literacy is correlated with poor outcomes in adults but is understudied in pediatrics. The current project aimed to determine the relationship between health literacy, adherence, and outcomes in pediatric liver transplant recipients. Hypotheses included a) parent and patient health literacy would be positively correlated; and b) low patient and/or parent health literacy would be negatively correlated with adherence and health outcomes. PATIENTS AND METHODS: Eligible participants were recruited during routine follow-up visits in a pediatric liver transplant clinic. Parents and patients (>13 years old) completed 2 measures of health literacy. Patients ≥18 years completed health literacy measures without corresponding parent surveys. Adherence variables and health outcomes were obtained from medical records. RESULTS: Seventy-nine patients across two sites completed the study. Variance in classification of health literacy between measures was observed; however, most parents (82%-100%) scored within an "adequate literacy" range. More adolescents scored in lower health literacy ranges relative to the parents. Markers of SES were positively correlated with health literacy. Parent health literacy was negatively associated with biopsy-proven rejection episodes and the number of hospitalizations; however, it was not associated with measures of tacrolimus adherence. There were no relationships observed between parent and adolescent health literacy. CONCLUSIONS: Health literacy is an important consideration in managing patient care; however, available measures demonstrate variability in capturing the skills of patients. Effective communication strategies may ameliorate admittedly small, but negative, impacts of limited health literacy on outcomes.

Quality Improvement Targeting Adherence During the Transition from a Pediatric to Adult Liver Transplant Clinic.

The transition from pediatric to adult transplant care is a high risk period for non-adherence and poor health outcomes. This article describes a quality improvement initiative integrated into a pediatric liver transplant program that focused on improving outcomes following the transfer from pediatric to adult liver transplant care. Using improvement science methodology, we evaluated the impact of our center's transition readiness skills (TRS) program by conducting a chart review of 45 pediatric liver transplant recipients who transferred to adult transplant care. Medication adherence, clinic attendance, and health status variables were examined for the year pre-transfer and first year post-transfer. 19 recipients transferred without participating in the TRS program (control group) and 26 recipients participated in the program prior to transferring to the adult clinic (TRS group). The TRS group was significantly older at the time of transfer, more adherent with medications, and more likely to attend their first adult clinic visit compared to the control group. Among the TRS group, better adolescent and parent regimen knowledge were associated with greater adherence to post-transfer clinic appointments. Transition planning should focus on the gradual shift in responsibility for health management tasks, including clinic attendance, from parent to adolescent. There may be support for extending transition support for at least 1 year post-transfer to promote adherence.

Ultrasound shear wave speed measurements correlate with liver fibrosis in children.

BACKGROUND: Little published research has shown the relationship between noninvasive US shear wave speed (SWS) measurements and degree of liver fibrosis as established by percutaneous biopsy in children. OBJECTIVE: To assess the relationship between liver US shear wave speed (SWS) measurements and parenchymal fibrosis in children. MATERIALS AND METHODS: Sixty-two children (0-18 years old) with known or suspected liver disease underwent same-day US shear wave elastography (SWE) and clinically ordered percutaneous core needle biopsy. SWE was performed just before the liver biopsy in the area targeted for sampling, using an Acuson S3000 US system with a 9L4 transducer; six SWS measurements were acquired using Virtual Touch Quantification (VTQ) and Virtual Touch IQ (VTIQ) modes. Biopsy specimens were scored for histological fibrosis and inflammation. Bivariate relationships were assessed using Pearson correlation, while multiple linear regression analysis was used to establish the relationship between SWS and predictor variables. Receiver operating characteristic (ROC) curves were created to assess the abilities of VTQ and VTIQ to discern low vs. high liver fibrosis (histological fibrosis scores 0-2 vs. 3-6). RESULTS: There were significant positive correlations between liver histological fibrosis score and VTQ (n = 49) and VTIQ (n = 48) mean shear wave speed measurements (r = 0.68 and r = 0.73; P-values <0.0001). There also were significant positive correlations between liver histological inflammation score and VTQ and VTIQ mean shear wave speed measurements (r = 0.47 and r = 0.44, and P = 0.0006 and P = 0.0016, respectively). For VTQ, both histological fibrosis (P < 0.0001) and inflammation (P = 0.04) scores were significant predictors of shear wave speed (model adjusted R (2) = 0.49). For VTIQ, only histological fibrosis score (P < 0.0001) was a significant predictor of shear wave speed (model adjusted R (2) = 0.56). ROC areas under the curve were 0.84 and 0.86 for VTQ and VTIQ, respectively. CONCLUSION: Liver US shear wave speed measurements increase with increasing parenchymal fibrosis in children.

Assessing allocation of responsibility for health management in pediatric liver transplant recipients.

Given the increased risk for non-adherence and poor health outcomes in late adolescence, there is a need for better methods to evaluate and improve the transition process as adolescent patients are prepared to be independent adults. This study assessed the psychometrics and concurrent validity of a newly developed measure of AoR for health management in pediatric liver transplant patients. A total of 48 patients and 37 parents completed a 13-item measure of AoR. We performed an exploratory PCA on survey results and used component scores to assess the relationship between AoR and age, age at transplant, adherence, and health outcomes. Two primary components were identified: communication with the healthcare system and self-management tasks. Parent perception of adolescent responsibility for tasks related to communicating with the healthcare system was correlated, in younger patients, with increased non-adherence while responsibility for tasks related to self-management was correlated, in older patients, with decreased non-adherence. These results support AoR as a two-domain construct, and they provide targets for monitoring and intervention as adolescent patients advance toward transfer.

Shear wave elastography helps differentiate biliary atresia from other neonatal/infantile liver diseases.

BACKGROUND: Biliary atresia is a rapidly progressive liver disease necessitating prompt diagnosis and surgical intervention, so it must be promptly distinguished from other neonatal/infantile liver diseases. OBJECTIVE: To determine whether US shear wave elastography (SWE) can differentiate biliary atresia from other neonatal/infantile liver diseases based on liver hardness. MATERIALS AND METHODS: Eleven children younger than 1 year who had suspected liver disease underwent anatomically and temporally-related hepatic shear wave elastography and clinically indicated percutaneous core needle biopsy. Shear wave elastography was performed immediately prior to liver biopsy at the targeted biopsy site using an Acuson S3000 US system/9L4 transducer (Siemens Medical Solutions USA, Malvern, PA). Shear wave elastography was performed using Virtual Touch Quantification (VTQ) and Virtual Touch IQ (VTIQ) modes, and six shear wave speed measurements were acquired from each subject for each mode. Children were placed in two groups based on histology, biliary atresia (n = 6) vs. non-biliary atresia (other neonatal/infantile liver diseases) (n = 5), and mean shear wave speed measurements were compared using the unpaired student's t-test (two-tailed). A P-value <0.05 was considered significant. RESULTS: Using the VTQ mode, mean liver shear wave speed was 2.08 ± 0.17 m/s for the biliary atresia group and 1.28 ± 0.13 m/s for the non-biliary atresia group (P < 0.0001). Using the VTIQ mode, mean liver shear wave speed was 3.14 ± 0.73 m/s for the biliary atresia group and 1.61 ± 0.23 m/s for the non-biliary atresia group (P = 0.003). Ishak liver fibrosis scores ranged from 3 to 6 for the biliary atresia group and from 0 to 1 for the non-biliary atresia group. CONCLUSION: Liver shear wave speed is abnormally increased in neonates and infants with biliary atresia.

Analysis of viral testing in nonacetaminophen pediatric acute liver failure.

OBJECTIVE: Viral infections are often suspected to cause pediatric acute liver failure (PALF), but large-scale studies have not been performed. We analyzed the results of viral testing among nonacetaminophen PALF study participants. METHODS: Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either causative viruses (CVs) or associated viruses (AVs). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included "viral," "indeterminate," and "other." RESULTS: Of 860 participants, 820 had at least 1 test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among "viral" (66/80 [82.5%]), "indeterminate" (52/420 [12.4%]), and "other" (48/320 [15.0%]) diagnoses. CVs accounted for 81/166 (48.8%) positive tests. Herpes simplex virus (HSV) was positive in 39/335 (11.6%) who were tested 26/103 (25.2%) and 13/232 (5.6%) among infants 0 to 6 and >6 months, respectively. HSV was not tested in 61.0% and 53% of the overall cohort and those 0 to 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. CONCLUSIONS: Viral testing in PALF occurs frequently but is often incomplete. The evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

A pilot study of the association between sleep disturbance in children with liver transplants and parent and family health-related quality of life.

OBJECTIVE: To investigate the relationship between sleep disturbance in children with liver transplants and parent and family health-related quality of life (HRQOL). METHOD: 47 parents of children with liver transplants completed measures of child sleep and family HRQOL. Relationships between sleep and HRQOL and differences in HRQOL between groups with scores above and below the cutoff on a pediatric sleep measure were examined. RESULTS: Parents endorsed higher rates of sleep-related breathing disorder (SRBD) and restless legs syndrome and periodic limb movements during sleep (RLS/PLMS) and lower HRQOL compared with published data. Significant correlations were found between SRBD and RLS/PLMS and HRQOL, and significant group differences in HRQOL were found between groups above and below the cutoff for behavior problems and RLS/PLMS. CONCLUSION: There are significant relationships between symptoms of SRBD and RLS/PLMS in children with liver transplants and family HRQOL. Behavior problems may account for these strong relationships.

Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

UNLABELLED: N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. CONCLUSION: NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

Relationship between sleep problems and health-related quality of life among pediatric liver transplant recipients.

Among adult liver transplant recipients (LTRs), sleep disturbances and fatigue are common. Sleep problems following pediatric liver transplantation may contribute to daytime fatigue and lower health-related quality of life (HRQOL). The aim of this cross-sectional study was to determine the impact of sleep problems on the HRQOL of pediatric LTRs using validated measures. Participants included 47 LTRs. Mean age of the LTRs was 10.9 ± 4.6 years, and mean time since transplantation was 6.2 ± 3.9 years. The primary indication for transplantation was biliary atresia (51%). According to parent reports, pediatric transplant recipients had symptoms of sleep-disordered breathing, excessive daytime sleepiness, daytime behavior problems, and restless legs; 40.4% of parents and 43.8% of children reported significantly lower total HRQOL for the recipients. Age, time since transplantation, and health status were not significantly related to the quality of life. Hierarchical regression analyses revealed that the sleep-disordered breathing subscale of the Pediatric Sleep Questionnaire accounted for significant variance in parent-proxy reports on the Pediatric Quality of Life (PedsQL) summary scales measuring children's psychosocial health (R(2) = 0.36, P < 0.001), physical health (R(2) = 0.19, P = 0.004), and total HRQOL (R(2) = 0.35, P < 0.001). Also, the sleep-disordered breathing subscale accounted for significant variance in the child self-reported school functioning scale (R(2) = 0.18, P = 0.03). Clinically significant sleep problems were more common among children with low total HRQOL. In conclusion, sleep problems were common in this cohort of pediatric LTRs and predicted significant variance in HRQOL. Prospective larger scale studies are needed to assess factors that contribute to sleep difficulties and low HRQOL in this population. The detection and treatment of significant sleep problems may benefit the HRQOL of pediatric LTRs.

Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study.

BACKGROUND: The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established. PATIENTS AND METHODS: The DILIN (Drug-Induced Liver Injury Network) Prospective Study is a longitudinal multicenter study designed to determine the etiologies, risk factors, and outcomes of suspected DILI. Between September 2004 and September 2009, 30 children ages 2 to 18 years with suspected DILI who met eligibility criteria were enrolled and studied for at least 6 months. RESULTS: Mean age was 14 years; 70% were girls. Antimicrobial (50%) and central nervous system agents (40%) were the most commonly implicated drug classes, with minocycline (4), isoniazid (3), azithromycin (3), atomoxetine (3), and lamotrigine (3) the leading agents. Median time from drug initiation to symptom onset was 32 days. Peak (median) liver chemistries were aspartate aminotransferase 503  U/L, alanine aminotransferase 727  U/L, alkaline phosphatase 331  U/L, and total bilirubin 3.9  mg/dL. Autoantibodies were common (64%). Liver injury pattern was hepatocellular 78%, cholestatic 13%, and mixed 9%. The DILI episode was scored: mild 32%, moderate 44%, severe 20%, and fatal (within 6 months) 4%. Causality assessment was definite 36%, very likely 36%, probable 16%, possible 8%, and unlikely 4%. Seven percent had persistent liver test abnormalities at 6-month follow-up suggesting chronic DILI. Liver biopsies from 12 children most frequently demonstrated chronic hepatitis or bile duct injury. CONCLUSIONS: Idiosyncratic DILI in children is most commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. The majority of patients recover, but morbidity and infrequent mortality are seen.

Transition of pediatric liver transplant recipients to adult care: patient and parent perspectives.

The need to prepare pediatric transplant recipients for the transfer to adult-centered transplant care has received increased attention. This study aimed to determine adolescent and young adult LTR and parent perceptions and attitudes about the transition process. LTR and their parents completed a survey assessing level of prior thought and interest in learning about transferring care, knowledge of the transition process, perceived importance of self-management skills, concerns about moving to the adult clinic, and responsibility for health management tasks. Responses were analyzed by age, gender, and time since transplantation. Participants included 46 LTR (mean age = 16.6 yr; range 12-21), and 31 parents. Recipients and parents reported moderate concern about transition, with leaving pediatric providers being a primary worry. LTR ≥16 yr reported greater health care responsibility and increased thought, interest, and knowledge about transition. There were significant differences between parent and LTR perceptions of health care responsibility, indicating that LTR perceive having more independence than what their parents report. Overall, results suggest that adolescent and young adult LTR and their parents perceive the importance of transitional care, but demonstrate poor knowledge of the process. There remains a need for improved transition planning for both adolescents and parents.

Immune response to rabies vaccination in pediatric transplant patients.

Children have become engaged in a wider variety of activities as the success of solid organ transplantation has improved. These activities can result in exposure to infectious agents for which there are no data documenting the efficacy of standard treatment in children on immunosuppressive therapy. This is a retrospective review of five OLT patients and three RT patients who were potentially exposed to rabies during camp. They completed the immunoprophylaxis treatment for rabies exposure outlined by the CDC in the 2003 Red Book. Rabies titers were followed for six to 12 months post-immunization. All five OLT patients were on tacrolimus. All three RT patients were on tacrolimus, mycophenolate mofetil, and prednisone. At the time of exposure median age was 10.0 yr (8.4-17.3). None of the subjects developed rabies. A positive rabies titer, indicative of successful immunization, was present by one month in seven subjects and all subjects by six months. Rabies vaccination in pediatric transplant patients is safe and associated with the successful production of antirabies titers.

Adherence and health-related quality of life in adolescent liver transplant recipients.

Adolescence is a particularly high-risk period for non-adherence with post-transplant medical regimens. There remains a lack of research investigating factors related to non-adherence in adolescent LT recipients. The present study empirically assessed the relationship between adherence and HRQOL in adolescent LT recipients. Participants included 25 adolescents (mean = 15.1 yr, range 12-17.9) and their parent/guardian(s). Adherence was assessed using multiple indices including clinician-conducted interviews, rate of clinic attendance, and s.d. of consecutive tacrolimus blood levels. HRQOL was examined using self-report and parent-proxy report on well-validated assessment measures. Results indicated that 76% of participants were non-adherent on at least one measure of adherence, and HRQOL was significantly lower than normative data for healthy children. Tacrolimus s.d. were significant related to poor HRQOL across domains of physical, school, and social functioning. Non-adherent adolescents reported poorer health perceptions, self-esteem, mental health, family cohesion, and more limitations in social and school activities related to physical, emotional, and behavioral problems. These results suggest that empirically based assessment of HRQOL may help identify those at highest risk for behavior, emotional and school difficulties, as well as non-adherence. The examination of tacrolimus s.d. may also help identify patients who may benefit from intervention to promote adherence and HRQOL. Prospective investigations are necessary to further identify the impact of HRQOL on adherence and long-term health outcomes to further guide clinical intervention.

Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group.

OBJECTIVES: To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors. STUDY DESIGN: A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained > or = 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ. RESULTS: The cause of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy. CONCLUSIONS: Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.

Immunization of children after solid organ transplantation.

The array of immunizations commonly used in childhood has risen in an attempt to prevent many of the potentially serious infections of infancy and childhood. In this article, the authors provide rational guidelines for vaccination of these children. The authors briefly review the susceptibilities caused by immunosuppression in these patients, discuss the problems with various immunizations, and make individual recommendations regarding the use of each vaccine. Most recommendations are based on inferences from populations that may not be directly comparable to the transplantation population (patients with HIV or cancer or patients who have undergone bone marrow transplant), from case reports, and from small series of patients. The best recommendations ultimately must await the results of controlled trials of immunization.