Feasibility and Acceptability of a mHealth Self-Management Intervention for Pediatric Transplant Families.

Families of pediatric solid organ transplant recipients need ongoing education and support in the first 30 days following hospital discharge for the transplantation. The purpose of this report is to describe the feasibility, acceptability, and preliminary efficacy of a mHealth family-self management intervention, (myFAMI), designed to improve post-discharge outcomes of coping, family quality of life, self-efficacy, family self-management, and utilization of health care resources. We enrolled 46 primary family members. myFAMI was feasible and acceptable; 81% (n=17/21) of family members completed the app at least 24/30 days (goal 80% completion rate). Family members generated 134 trigger alerts and received a nurse response within the goal timeframe of < 2 h 99% of the time. Although there were no significant differences between groups, primary outcomes were in the expected direction. The intervention was well received and is feasible for future post-discharge interventions for families of children who receive an organ transplant.

Transcriptional Analysis of Liver Tissue Identifies Distinct Phenotypes of Indeterminate Pediatric Acute Liver Failure.

Many patients with indeterminate pediatric acute liver failure (PALF) have evidence of T-cell driven immune injury; however, the precise inflammatory pathways are not well defined. We have characterized the hepatic cytokine and transcriptional signatures of patients with PALF. A retrospective review was performed on 22 children presenting with indeterminate (IND-PALF; n = 17) or other known diagnoses (DX-PALF; n = 6) with available archived liver tissue. Specimens were stained for clusters of differentiation 8 (CD8) T cells and scored as dense, moderate, or minimal. Measurement of immune analytes and RNA sequencing (RNA-seq) was performed on whole-liver tissue. Immune analyte data were analyzed by principal component analysis, and RNA-seq was analyzed by unsupervised hierarchical clustering, differential gene expression, and gene-set enrichment analysis. Most patients with IND-PALF (94%) had dense/moderate CD8 staining and were characterized by Th1 immune analytes including tumor necrosis factor α, interferon γ (IFN-γ), interleukin (IL) 1ß, IL-12, C-X-C motif chemokine ligand (CXCL) 9, and CXCL12. Transcriptional analyses identified two transcriptional PALF phenotypes. Most patients in group 1 (91%) had IND-PALF and dense/moderate CD8 staining. This group was characterized by increased expression of genes and cell subset-specific signatures related to innate inflammation, T-cell activation, and antigen stimulation. Group 1 expressed significantly higher levels of gene signatures for regulatory T cells, macrophages, Th1 cells, T effector memory cells, cytotoxic T cells, and activated dendritic cells (adjusted P < 0.05). In contrast, patients in group 2 exhibited increased expression for genes involved in metabolic processes. Conclusion: Patients with IND-PALF have evidence of a Th1-mediated inflammatory response driven by IFN-γ. Transcriptional analyses suggest that a complex immune network may regulate an immune-driven PALF phenotype with less evidence of metabolic processes. These findings provide insight into mechanisms of hepatic injury in PALF, areas for future research, and potential therapeutic targets.

Applying an Age-specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure.

OBJECTIVE: Neonatal acute liver failure (ALF) is a rare disease with high mortality for which no standard age-specific definition exists. To advance the understanding of neonatal ALF, we characterize the etiology, presenting features, treatment, and outcomes in infants within 1 month of life. METHODS: We performed a single-center 11-year retrospective chart review of neonates ≤30 days of life with ALF as defined by an INR of ≥2.0. Comparisons were made by etiology and survival with native liver (SNL). Estimated survival was performed using the Kaplan-Meier method. RESULTS: Forty-three patients met inclusion criteria for neonatal ALF. Etiologies included viral infection (23%), gestational alloimmune liver disease with neonatal hemochromatosis (GALD-NH) (21%), cardiac-associated ischemia (16%), other ischemia (14%), genetic etiologies (9%), Trisomy 21-associated myelodysplasia (TAM) (7%), hemophagocytic lymphohistiocytosis (HLH) (2%), and not identified (7%). Infants with viral etiologies had the highest alanine aminotransferase (ALT) at presentation (1179 IU/L, interquartile range [IQR] 683-1585 IU/L) in contrast to low levels in GALD-NH (23 IU/L, IQR 18-64 IU/L). Across all etiologies, only 33% were alive at 1 year. Overall median survival was 74 days; 17 days for viral infection and 74 days for GALD-NH. Among laboratory values at presentation, alpha-fetoprotein (AFP) was significantly higher in patients that survived with their native liver (P = 0.04). CONCLUSIONS: Overall, outcome for neonatal ALF is poor. Although initial laboratory values can differentiate viral infection or GALD-NH, further studies are needed to identify laboratory parameters that predict SNL by etiology to ultimately improve patient outcomes.

Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.

OBJECTIVES: In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis. METHODS: PALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRß) sequencing. RESULTS: Dense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin (88% vs 50%, P = 0.03) and CD103 (82% vs 40%, P = 0.02) staining compared with DX-PALF subjects. TCRß sequencing of 15 IND-PALF cases demonstrated increased clonal overlap compared with 6 DX-PALF cases (P = 0.002). CONCLUSIONS: Dense infiltration of effector Trm CD8 T cells characterizes liver tissue from IND-PALF subjects. Increased clonality suggests the T-cell expansion is antigen(s)-driven as opposed to a nonspecific inflammatory response. These findings support CD8 staining as a new biomarker of the activated CD8 T-cell PALF phenotype. Future studies are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.

Health utility and quality of life in pediatric liver transplant recipients.

To measure HU and HRQOL in pediatric liver transplant (LT) recipients, a cross-sectional study of patient-parent dyads was conducted. Direct HU were assessed in 48 adolescents ≥12 years using SG and TTO techniques. Indirect HU were measured by Health Utility Index 2 and HUI3 for subjects ≥12 years and CHU9D for ≥7 years. Patients reported HRQOL using PedsQL™ GC and PedsQL™ TM. A total of 108 dyads participated (55.6% female; 73.2% Caucasian; 42.6% biliary atresia; 35.2% living donor; 37.0% Medicaid). Mean age at survey was 13.6 ± 3.5 years, and time from LT was 8.9 ± 4.9 years. 61.2% were on monotherapy, 25 (23.2%) had acute rejection within 3 years, and 15 (13.9%) had a biliary obstruction within 5 years. Mean indirect HU and HRQOL scores by child report were lower than norms (P < .001). LRD recipients had higher PedsQL™ GC, PedsQL™ TM, and HUI3 scores (P < .01). HU in pediatric LT recipients are lower than norms. Availability of HU scores for post-transplant health states will enable measurement of quality-adjusted life years for future comparative effectiveness studies.

Admission Characteristics Identify Risk of Pediatric Acute-on-Chronic Liver Failure.

OBJECTIVES: Acute-on-chronic liver failure (ACLF) is well-studied in adults and characterized by decompensated cirrhosis, multi-organ failure, and early mortality. Studies of ACLF in children are limited. We sought to characterize the prevalence and clinical factors associated with pediatric ACLF (PACLF). METHODS: A retrospective review of children 3 months to 18 years listed for liver transplantation and hospitalized for decompensated cirrhosis between January 2007 and December 2017 at a single pediatric hospital. Primary outcome was the development of PACLF, characterized as failure of at least 1 extrahepatic organ (mechanical ventilation, renal replacement therapy, vasoactive medications, grade III/IV hepatic encephalopathy). Characteristics were recorded for each hospitalization. RESULTS: Sixty-six patients had 186 hospitalizations with mean age at admission 4.0 ±â€Š5.6 years and diagnosis of biliary atresia (BA) in 65%. PACLF developed in 20 patients during 23 hospitalizations (12%) and respiratory failure was most common (17/23, 74%). Duration of intensive care unit stay, 13.1 ±â€Š1.2 days versus 0.6 ±â€Š0.6 days (P < 0.001) and length of stay, 24.3 ±â€Š5.0 days versus 7.9 ±â€Š1.9 days (P = 0.003) were longer in PACLF compared with non-PACLF. Mortality during PACLF hospitalizations was 22%. Clinical factors associated with PACLF were reported from a generalized linear mixed model and included increased admission creatinine (P < 0.0001), increased aspartate aminotransferase (AST) (P = 0.014), increased international normalized ration (INR) (P = 0.0015), and a positive blood culture (P = 0.007). CONCLUSION: In this pediatric series, PACLF developed in 12% of hospitalizations and mortality was high. Admission creatinine, AST, INR, and presence of a positive blood culture were associated with PACLF development.

Health-Related Quality of Life and Cognitive Functioning in Pediatric Liver Transplant Recipients.

The goal of this work was to examine the change in health-related quality of life (HRQOL) and cognitive functioning from early childhood to adolescence in pediatric liver transplantation (LT) recipients. Patients were recruited from 8 North American centers through the Studies of Pediatric Liver Transplantation consortium. A total of 79 participants, ages 11-18 years, previously tested at age 5-6 years in the Functional Outcomes Group study were identified as surviving most recent LT by 2 years and in stable medical follow-up. The Pediatric Quality of Life 4.0 Generic Core Scale, Pediatric Quality of Life Cognitive Function Scale, and PROMIS Pediatric Cognitive Function tool were distributed to families electronically. Data were analyzed using repeated measures and paired t tests. Predictive variables were analyzed using univariate regression analysis. Of the 69 families contacted, 65 (94.2%) parents and 61 (88.4%) children completed surveys. Median age of participants was 16.1 years (range, 12.9-18.0 years), 55.4% were female, 33.8% were nonwhite, and 84.0% of primary caregivers had received at least some college education. Median age at LT was 1.1 years (range, 0.1-4.8 years). The majority of participants (86.2%) were not hospitalized in the last year. According to parents, adolescents had worse HRQOL and cognitive functioning compared with healthy children in all domains. Adolescents reported HRQOL similar to healthy children in all domains except psychosocial, school, and cognitive functioning (P = 0.02; P < 0.001; P = 0.04). Participants showed no improvement in HRQOL or cognitive functioning over time. For cognitive and school functioning, 60.0% and 50.8% of parents reported "poor" functioning, respectively (>1 standard deviation below the healthy mean). Deficits in HRQOL seem to persist in adolescence. Over half of adolescent LT recipients appear to be at risk for poor school and cognitive functioning, likely reflecting attention and executive function deficits.

A Pilot Study of a Screening Tool for Pediatric Minimal Hepatic Encephalopathy.

OBJECTIVES: Despite the need for monitoring cognition for minimal hepatic encephalopathy (MHE) in children with portal hypertension, few screening methods exist. The Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Perceived Cognitive Function (PedsPCF) item bank, a 43-item parent- and self-report questionnaire, could be a useful screening tool. This study aimed to evaluate the PedsPCF item bank as a screening tool and explore its correlation with other neurocognitive measures and clinical indicators of portal hypertension. METHODS: Pediatric patients with portal hypertension were recruited at Lurie Children's Liver Clinic. A short battery of neuropsychological tests tapping attention, executive functioning, and fine motor speed was administered along with surveys of cognitive functioning (PedsPCF, Behavior Rating Inventory of Executive Function; BRIEF) and quality of life (PROMIS Pediatric-25 Profile). RESULTS: Eighteen patients participated (ages 8--17). The PedsPCF correlated well with the BRIEF but did not correlate with neurocognitive testing. Qualitative heatmap analysis of the relationship between z-scores and clinical signs of portal hypertension suggests the PedsPCF is less sensitive than the BRIEF. The fine motor task (Grooved Pegboard) appears to offer the highest sensitivity of the tests administered and is also relatively quick and easy to administer. CONCLUSIONS: Elements of the battery show promise in this small pilot sample. The BRIEF and the Grooved Pegboard may hold the most potential for screening in the clinical setting. Further study is necessary to examine this question in a larger multicenter sample.

Low Insulin-like Growth Factor-1 Influences Fatigue and Quality of Life in Children With Inflammatory Bowel Disease.

OBJECTIVE: Fatigue is common among patients with inflammatory bowel disease (IBD). Proinflammatory cytokines are elevated in chronic inflammation and can induce "sickness behaviors," such as fatigue. Chronic inflammatory states also lead to growth hormone resistance, demonstrated by low levels of insulin-like growth factor (IGF-1) and elevated growth hormone. This study evaluated the relationship between IGF-1, proinflammatory cytokine levels, and fatigue in patients with IBD. METHODS: In this prospective study children with IBD, ages 10 to 16 years, were recruited from a subspecialty ambulatory clinic. Participants and their parents completed age-appropriate generic and disease-specific health-related quality of life (HRQOL) instruments. Serum samples obtained at the same encounter were analyzed for Th17 cytokine and IGF-1 levels. HRQOL scores were compared to a healthy sample and HRQOL scores and cytokine levels were compared by IGF-1 z score quartiles. RESULTS: A total of 67 patients with IBD were recruited, median age of 13.7 years (interquartile range, 11.7-15.3). Forty-eight (72%) had inactive disease based on Physician Global Assessment. Patients with IBD reported lower generic HRQOL (P = 0.0006) and more fatigue (P = 0.0004) than a healthy sample. Patients with IGF-1 z scores in the lowest quartile had significantly lower disease-specific HRQOL (P = 0.01) and more fatigue (P = 0.02) than the remainder of the cohort. Serum interleukin (IL)-10, IL-17A, IL-6, and interferon-γ were significantly higher in patients with IBD with IGF-1 z scores in the lowest quartile (P < 0.05). CONCLUSIONS: Children with subclinical IBD experience more fatigue and lower generic HRQOL than healthy children. Lower IGF-1 z scores are associated with more fatigue, and this relationship may be mediated through proinflammatory cytokines.

Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure.

OBJECTIVE: To determine health-related quality of life (HRQoL) and neurocognitive impairment in survivors of pediatric acute liver failure (PALF). STUDY DESIGN: A longitudinal prospective study was conducted. At 6 and 12 months after PALF presentation, surveys of HRQoL were completed for 2- to 19-year-olds and executive functioning for ages 2-16 years. At 12 months, patients 3-16 years of age completed neurocognitive testing. HRQoL scores were compared with a healthy, matched sample. Neurocognitive scores were compared with norms; executive functioning scores were examined categorically. RESULTS: A total of 52 parent-report HRQoL surveys were completed at 6 months, 48 at 12 months; 25 patients completed neurocognitive testing. The median age at 6 months was 7.9 years (range 3.5-15.0), and final diagnosis was indeterminate for 46.2% (n = 24). Self and parent-report on Pediatric Quality of Life Inventory Generic and Multidimensional Fatigue scales fell below the healthy sample at 6 months and 12 months (almost all P < .001). Children reported lower mean scores on cognitive fatigue at 12 months (60.91 ± 22.99) compared with 6 months (73.61 ± 27.49, P = .006) . The distribution of Behavior Rating Inventory of Executive Function scores was shifted downward on parent-report (preschool) for all indices at 6 months (n = 14, P ≤ .003); Global Executive Composite and Emergent Metacognition at 12 months (n = 10, P = .03). Visual Motor Integration (VMI-6) Copying (mean = 90.3 ± 13.8, P = .0002) and VMI-6 Motor Coordination (mean = 85.1 ± 15.2 P = .0002) fell below norms, but full scale IQ (Wechsler Scales) and Attention (Conners' Continuous Performance Test) did not. CONCLUSIONS: Survivors of PALF appear to show deficits in motor skills, executive functioning, HRQoL, and evidence for worsening cognitive fatigue from 6 to 12 months following PALF presentation.

Recruiting a representative sample in adherence research-The MALT multisite prospective cohort study experience.

Medication adherence is an important determinant of transplant outcomes. Attempts to investigate adherence are frequently undermined by selection bias: It is very hard to recruit and retain non-adherent patients in research efforts. This manuscript presents recruitment strategies and results from the MALT (Medication Adherence in children who had a Liver Transplant) multisite prospective cohort study. MALT sites recruited 400 pediatric liver transplant patients who agreed to be followed for 2 years. The primary purpose was to determine whether a marker of adherence, the Medication Level Variability Index (MLVI), predicts rejection outcomes. The present manuscript describes methods used in MALT to ensure that a representative sample was recruited, and presents detailed recruitment results. MALT sites were able to recruit a nationally representative sample, as determined by a comparison between the MALT cohort and a national sample of transplant recipients. Strategies that helped ensure that the sample was representative included monitoring of the outcome measure in comparison with a national sample, drastically limiting patient burden, and specific recruitment methods. We discuss the importance of a representative sample in adherence research and recommend that future efforts to study adherence pay special attention to sample characteristics.

Impaired physical function following pediatric LT.

The purpose of this article is to investigate the spectrum of physical function of pediatric liver transplantation (LT) recipients 12-24 months after LT. Review data were collected through the functional outcomes group, an ancillary study of the Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12-24 months. Children ≥ 8 years and parents completed the Pediatric Quality of Life Inventory™ 4.0 generic core scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n = 1658) and between survivors with optimal versus nonoptimal health. A total of 263 patients were included. Median age at transplant and survey was 4.8 years (interquartile range [IQR], 1.3-11.4 years) and 5.9 years (IQR, 2.6-13.1 years), respectively. The mean physical functioning score on child and parent reports were 81.2 ± 17.3 and 77.1 ± 23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (P < 0.001); 32.9% of patients and 35.0% of parents reported a physical function score <75, which is > 1 standard deviation below the mean of a healthy population. Physical functioning scores were significantly higher in survivors with optimal health than those with nonoptimal health (P < 0.01). There was a significant relationship between emotional functioning and physical functioning scores for LT recipients (r = 0.69; P < 0.001). In multivariate analysis, primary disease, height z score < -1.64 at longterm follow-up (LTF) visit, > 4 days of hospitalization since LTF visit, and not being listed as status 1 were predictors of poor physical function. In conclusion, pediatric LT recipients 1-2 years after LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and the development of rehabilitation programs may be important.

Pediatric solid organ transplant recipients: transition to home and chronic illness care.

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care.

Neuropsychological functioning and health-related quality of life: pediatric acute liver failure study group results.

OBJECTIVES: Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. METHODS: This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. RESULTS: A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001). CONCLUSIONS: Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.

Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation.

OBJECTIVE: To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. STUDY DESIGN: Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). RESULTS: Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. CONCLUSIONS: More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome.

Transition from hospital to home following pediatric solid organ transplant: qualitative findings of parent experience.

Transplant providers are challenged to determine appropriate interventions for patients and families due to limited published research regarding the context of the post-discharge experience from the perspective of parents of transplanted children. The purpose of this study is to describe the parent perspective of the transition from hospital to home following their child's solid organ transplant. Within a mixed-methods design, 37 parents of pediatric heart, kidney, and liver transplant recipients from three pediatric hospitals responded to qualitative interview questions on the day of hospital discharge and three wk following hospital discharge. Insight to the discharge preparation process revealed necessary education components. Post-discharge themes were identified for coping, knowledge, and adherence. The parents' responses provide awareness as to specific stressors and concerns parents are faced with when their child is discharged from the hospital after solid organ transplant and opportunities for ways the transplant team can provide support.

Factors predicting health-related quality of life in pediatric liver transplant recipients in the functional outcomes group.

Data from 997 pediatric LT recipients were used to model demographic and medical variables as predictors of lower levels of HRQOL. Data were collected through SPLIT FOG project. Patients were between 2 and 18 yr of age and survived LT by at least 12 months. Parents and children (age ≥ 8 yr) completed PedsQL™ 4.0 Generic Core and CF Scales at one time point. Demographic and medical variables were obtained from SPLIT. HRQOL scores were categorized as "poor" based on lower 25% of scores for each measure. Logistic regression models were generated. Single-parent households (OR 1.94, CI 1.13-3.33, p = 0.017), anti-seizure medications (OR 3.99, CI 1.26-12.70, p = 0.019), and number of days hospitalized (OR 1.03, CI 1.01-1.06, p = 0.0067) were associated with lower self-reported HRQOL. Parent data identified increasing age at transplant, age 5-12 yr at survey, hospitalization >21 days at LT, re-operations, diabetes, and growth failure at LT as additional predictors of generic HRQOL. Male gender, single-parent households, higher bilirubin levels at LT, and use of anti-seizure medication predicted lower cognitive function scores. HRQOL following pediatric LT is related to medical and demographic variables.

Health-related quality of life in pediatric liver transplant recipients compared with other chronic disease groups.

This cross-sectional, multicenter cohort study compares the level of HRQOL of pediatric LT recipients to children with other chronic health conditions. LT sample included 873 children who survived at least 12 months following LT. Six chronic disease samples were compiled from numerous studies, including over 800 patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end-stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured from both the parental and patient perspective using the PedsQL™ 4.0 Generic Core Scales. Pediatric LT patients reported better physical health than children with JRA. According to parents, pediatric LT recipients had better HRQOL than children on renal dialysis on all domains except school functioning. Across all domains but emotional functioning, pediatric LT recipients reported significantly lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients reported HRQOL comparable to that of children who had undergone renal transplantation and patients with cancer in remission. Pediatric LT patients manifested impaired HRQOL similar to that of children with chronic diseases and these data suggest that they face ongoing challenges that warrant monitoring and indicate a need for interventions to improve their HRQOL.

The PedsQL™ Infant Scales: feasibility, internal consistency reliability, and validity in healthy and ill infants.

OBJECTIVE: The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life (HRQOL) and disease-specific symptoms in children and adolescents ages 2-18. The new PedsQL™ Infant Scales were designed as a generic HRQOL instrument specifically for healthy and ill infants ages 1-24 months. The objective of this study was to report on the initial feasibility, internal consistency reliability, and validity of the PedsQL™ Infant Scales in healthy, acutely ill, and chronically ill infants. METHODS: The 36-item (ages 1-12 months) and 45-item (ages 13-24 months) PedsQL™ Infant Scales (Physical Functioning, Physical Symptoms, Emotional Functioning, Social Functioning, Cognitive Functioning) were completed by 683 parents of healthy, acutely ill, and chronically ill infants. RESULTS: The PedsQL™ Infant Scales evidenced minimal missing responses, achieved excellent internal consistency reliability for the Total Scale Scores (α = 0.92), distinguished between healthy infants and acutely and chronically ill infants, and demonstrated a confirmatory factor structure largely consistent with the a priori conceptual model. CONCLUSIONS: The results demonstrate the initial measurement properties of the PedsQL™ Infant Scales in healthy and ill infants. The findings suggest that the PedsQL™ Infant Scales may be utilized in the evaluation of generic HRQOL in infants ages 1-24 months.

PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients: feasibility, reliability, and validity.

OBJECTIVE: The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. The PedsQL™ Cognitive Functioning Scale was developed as a brief generic symptom-specific instrument to measure cognitive functioning. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients. METHODS: The 6-item PedsQL™ Cognitive Functioning Scale and the PedsQL™ 4.0 Generic Core Scales were completed by pediatric liver transplant recipients ages 8-18 years (n = 215) and parents of pediatric liver transplant recipients ages 2-18 years (n = 502). Both patient self-report and parent proxy-report were available for 212 cases. The 72-item Behavior Rating Inventory of Executive Function (BRIEF), a widely validated measure of executive functioning, was completed by 100 parents and 56 teachers on a subset of patients. RESULTS: The PedsQL™ Cognitive Functioning Scale demonstrated minimal missing responses (0.0%, child report, 0.67%, parent report), achieved excellent reliability (α = 0.88 child report, 0.94 parent report), distinguished between pediatric patients with liver transplants and healthy children supporting discriminant validity, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales and the BRIEF supporting construct and concurrent validity, respectively. Pediatric liver transplants recipients experienced cognitive functioning comparable to long-term pediatric cancer survivors. CONCLUSIONS: The results demonstrate the feasibility, reliability, discriminant, construct, and concurrent validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.