Transition to adult care for pediatric liver transplant recipients: the Western Australian experience

Transition to adult care is a vulnerable period for pediatric transplant recipients and is associated with reduced medication compliance, graft loss, and increased mortality. Psychosocial outcomes in young adults differ between pediatric transplant recipients and their healthy peers. We conducted a single‐center, retrospective cohort study of all pediatric liver transplant recipients who were transitioned through our center. This study aimed to assess the outcomes of transitioned pediatric liver transplant recipients at an Australian center, including mortality, adherence, and psychosocial morbidity. The 1‐ and 5‐year survival rates following transition were 100% and 92%, respectively. There were no episodes of late rejection. In total, 66.7% of patients were compliant with immunosuppression and 61.1% of patients were compliant with clinic attendance. There was a significant relationship between medication compliance and clinic attendance, as well as presence of psychological issues with clinic non‐attendance. Psychosocial outcomes were in keeping with age‐matched data from the general population. All patients were employed or studying following transition. This is the first study of its kind in the Australian population, and outcomes were superior to published international data. Despite the demonstrated good outcomes, transition programs may improve healthcare engagement in this cohort.     

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.     

Transition readiness,adolescent responsibility,and executive functioning among pediatric transplant recipients: Caregivers' perspectives

This study aimed both to evaluate caregivers' perspectives of EF and transition readiness among adolescent transplant recipients and to examine the indirect effects of adolescent responsibility and parent involvement across domains of EF. Fifty‐seven caregivers of adolescent solid organ transplant recipients participated in this study and completed measures of adolescent EF, transition readiness, responsibility in healthcare behavior, and parent involvement. Bootstrapping procedures were used to test indirect effects. Caregiver report of adolescent EF was significantly related to transition readiness among transplant recipients. Significant indirect effects were found for adolescent responsibility but not parent involvement. No significant differences were found between metacognitive and behavioral regulation domains of EF in the association with transition readiness. Assessment of adolescent EF skills may help guide the development of individualized transition readiness guidelines to promote successful gains in self‐management abilities as well as eventual transfer to adult medical services.     

Cell phone support to improve medication adherence among solid organ transplant recipients

For many adolescent and young adult solid organ transplant recipients, medication non‐adherence is a mortal issue. This study investigated the feasibility, acceptability, and potential efficacy of a 12‐week cell phone support intervention to improve immunosuppressant medication adherence. A small sample (N = 8) of non‐adherent adolescent and young adult transplant recipients, aged 15‐20.5 years, was enrolled. Cell phone support consisted of short calls each weekday including medication reminders, discussion of needs, problem‐solving support, and promotion of clinic and community resources. Changes in adherence were measured by self‐report and laboratory values, and intervention acceptability, adherence barriers, social support, depression, and substance use were assessed by self‐report. Pre‐post effect sizes showed medium‐to‐large improvements in adherence, lasting through a 12‐week follow‐up assessment. There were also small‐to‐medium changes in adherence barriers, social support, and depression. However, acceptability and feasibility were limited, due to a low rate of enrollment by eligible male participants. Cell phone support interventions may promote medication adherence among adolescents and young adults. Cell phone support warrants further investigation, including a randomized controlled trial to evaluate efficacy.     

Psychosocial predictors of medication non‐adherence in pediatric organ transplantation: A systematic review

Adherence to immunosuppressant medication is critical to health and quality‐of‐life outcomes for children who have received a solid organ transplant. Research on the psychological and social predictors of medication adherence is essential to the advancement of pretransplant assessments and transplant psychosocial services. Despite the importance of identifying risk factors, the literature remains limited regarding psychosocial predictors of non‐adherence. A systematic search was conducted to identify studies of the psychosocial predictors of post‐transplant medication non‐adherence in pediatric solid organ transplantation. From 1363 studies identified in searches of empirical literature, a final sample consisted of 54 publications representing 49 unique studies. Findings regarding psychosocial predictors were inconsistent with non‐adherence associated largely with adolescence, racial/ethnic minority status, and presence of mental health issues. Familial predictors of non‐adherence problems included single‐parent households, lower socioeconomic status, lower family cohesion, presence of family conflict, and poor family communication. Several studies reported an association between non‐adherence and social pressures (eg, peer social interaction, wanting to feel normal) among adolescent transplant recipients. While significant methodological and substantive gaps remain in this body of knowledge, this review synthesizes current evidence for assessment for transplant clinicians and researchers.     

Preparing for transition: The effects of a structured transition program on adolescent heart transplant patients’ adherence and transplant knowledge

Transition to adult health care has become a mainstream focus in pediatric health care as a higher percentage of patients are surviving into adulthood. This study investigated the success of a structured educational transition program in improving pediatric heart transplant patients’ overall medical knowledge, medication adherence, readiness to transition, as well as parental perceptions of their child's readiness to transition to aid in the successful transition to an adult heart transplant program. Patients underwent a structured transition program over 2 years that included a total of seven 2‐hour educational sessions hosted quarterly. This study comprised of a retrospective review of 12 heart transplant patients between the ages of 16‐22 years . Test results indicated a statistically significant increase in overall medical knowledge scores from presession assessment compared to post‐session assessment. Participants remained confident in their ability to transition throughout the program. Further, a statistically significant decrease in participant non‐adherence was observed, as percentage of calcineurin inhibitor levels determined to be out of range decreased over the course of the program. Results suggest that a structured transition program is effective in improving overall patient medical knowledge in relation to their heart transplant and enhancing patient medication adherence. To effectively facilitate transition, pediatric providers, caregivers, and patients must communicate to provide a purposeful planned transition experience from pediatric to adult health care.     

Medication adherence in the transition of adolescent kidney transplant recipients to the adult care

Non‐adherence is common in adolescent and young adult kidney transplant recipients, leading to adverse graft outcomes. The aim of this study was to determine whether adherence to immunosuppressant medications changes during transition from a pediatric to an adult program within the same transplant center. Adherence was assessed for a period of two yr before and two yr after the transfer. Subtherapeutic trough levels of serum tacrolimus and level variability were used as measures of adherence. Twenty‐five patients were transitioned between 1996 and 2011 at the median age of 22.3 [IQR 21.6–23.0] yr. Young adults 21–25 yr of age (n = 26) and non‐transitioned adolescents 17–21 yr of age (currently followed in the program, n = 24 and those that lost their grafts prior to the transfer, 22) formed the comparison groups. In the transitioned group, adherence prior to the transfer was not significantly different from the adherence after the transfer (p = 0.53). The rate of non‐adherence in the group of non‐transitioned adolescents who lost their grafts (68%) was significantly higher than in the transitioned group (32%, p = 0.01). In the group of young adults, adherence was not significantly different from the transitioned group (p = 0.27). Thus, transition was not associated with differences in medication adherence in this single‐center study. Large‐scale studies are needed to evaluate the national data on medication adherence after transfer.     

Predictors of neuropsychological functioning and medication adherence in pediatric heart transplant recipients referred for neuropsychological evaluation

Children who undergo heart transplantation are at risk for long‐term neurodevelopmental sequelae secondary to heart disease and its treatment. Detailed neuropsychological profiles in clinical sample status post‐pediatric heart transplantation are sparse in the literature, and there is little information regarding predictors of neuropsychological functioning or how it relates to medication adherence in this population. The present study examined these questions in a retrospective analysis of 27 pediatric heart transplantation recipients referred for clinical neuropsychological evaluation. The sample demonstrated mild‐to‐moderate decrements across domains of neuropsychological functioning. Children with premorbid congenital heart disease performed more poorly in working memory, word reading, and parent‐rated conceptual adaptive skills compared to children with premorbid cardiomyopathy. Additionally, a higher number of rejection episodes were related to poorer verbal memory. Children with parent‐reported attention problems had better adherence to immunosuppressant medication, which may have represented greater caregiver involvement in medication management. Taken together, clinically referred children with history of heart transplantation showed broad‐based difficulties across neuropsychological domains according to formal testing and parent rating scales. This population requires routine neuropsychological monitoring and intervention.     

Growing pains: non-adherence with the immunosuppressive regimen in adolescent transplant recipients

One-year graft and patient survival are better in adolescent transplant recipients (age 11-19 years) than in younger (age < 11 years) pediatric transplant recipients. However, several groups found that long-term outcomes (> i.e. 5 year post-transplant) in the adolescent age group are significantly worse than in younger transplant recipients. A behavioral factor that could explain an important part of the poorer clinical outcome in adolescent transplant recipients is non-compliance with medication taking. Adolescents, like all organ transplant recipients irrespective of their age, must adhere to a life-long immunosuppressive regimen in addition to other aspects of their therapeutic regimen. Therefore, adolescent transplant recipients, as all transplant patients, should be regarded as a chronically ill patient population in whom behavioral and psychosocial management is equally important as state-of-the-art medical management. This paper provides an overview of the current knowledge on prevalence, clinical consequences, and risk-factors for non-compliance with the immunosuppressive regimen in adolescent transplant recipients and offers some suggestions for adolescent-tailored interventions to improve medication adherence.     

Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients

Abstract:  Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.     

A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect

Non‐adherence to immunosuppressant medications is an important risk factor for graft dysfunction. To evaluate the effectiveness of adherence‐enhancing interventions, we reviewed adherence intervention studies in solid organ transplant recipients (all ages). Using the following databases: PsycINFO, PubMed, Scopus, and ScienceDirect, we identified 41 eligible studies. Only three non‐randomized trials showed a possible positive effect on objective indicators of transplant outcomes (such as rejection, liver enzyme levels, kidney function). None of the 21 RCTs showed an improvement in transplant outcomes. Three studies showed a higher rate of adverse events in the intervention group as compared with controls, although this may be related to ascertainment bias. Improvement in adherence as measured indirectly (eg, with electronic monitoring devices) was not aligned with effects on transplant outcomes. We conclude that adherence interventions, to date, have largely been ineffective in improving transplant outcomes. To improve this track record, intervention efforts may wish to concentrate on non‐adherent patients (rather than use convenience sampling, which excludes many of the patients who need the intervention), use direct measures of adherence to guide the interventions, and employ strategies that are intensive and yet engaging enough to ensure that non‐adherent patients are able to participate.     

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.     

Longitudinal stability of medication adherence among adolescent solid organ transplant recipients

Solid organ transplantation requires ongoing adherence to immunosuppressants and other medications. Although adolescence is a risk factor for poor medication‐taking, little is known about the patterns of adherence within individuals over time. This study aimed to examine the stability of adherence over time using three different assessment techniques. Sixty‐six AYA transplant recipients and/or their caregiver completed interviews of adherence at baseline and at least one yr later. Serum immunosuppressant assay levels were collected via medical chart review. Non‐adherence percentages based on AYA report, caregiver report, and bioassay did not differ from Time 1 to Time 2. However, correlations for these measures across time were non‐significant. Further, the majority of AYAs shifted to a different adherence category from Time 1 to Time 2. Overall, these results demonstrate individual variability in non‐adherence over the course of adolescence and young adulthood and highlight the importance of frequent assessment across time for solid organ transplant recipients.     

Measuring family management of transplant tasks: The transplant responsibility questionnaire

Little is known about how parents and youth perceive their roles in post‐transplant management and how this relates to post‐transplant adherence. The goals of this study are to (1) describe a new measure, the TRQ, (2) to describe parent and child performance on the TRQ, and to (3) determine the relationship between the TRQ and adherence. We hypothesized that older youth would describe higher post‐transplant self‐care behaviors, parents would underestimate youth self‐care, and greater parent involvement would be associated with better adherence. Participants included 59 parent–child dyads. Inclusion criteria included: (i) youth aged 7–18 yr and (ii) at least three months post‐kidney or post‐liver transplant. Parents and youth completed the TRQ, and adherence was measured by s.d. of sequential immunosuppressant blood levels. Youth perceived greater levels of self‐care than their parents perceived. Older youth reportedly engaged in more self‐care than younger youth. Less than 25% of the sample was non‐adherent, and non‐adherence was unrelated to performance on the TRQ. The TRQ may have utility as a clinical tool to address areas for improvement in youth self‐care. The high degree of parental involvement likely explains the high degree of adherence in this sample.     

Adolescent transplant recipients as peer mentors: A program to improve self‐management and health‐related quality of life

The purpose of this study was to examine the safety, feasibility, acceptability, and preliminary efficacy of a cross‐age peer mentoring program created to improve adherence and psychosocial outcomes for pediatric liver transplant recipients. Twenty‐two participants were assigned to a “mentor now” or “mentor later” waitlist control group. Tacrolimus SD, a validated measure of adherence, was assessed for six months pre‐ and post‐intervention for both groups. Self‐report measures of self‐management and HRQOL were completed at recruitment and three months after training. Participant report indicated the acceptability of the intervention. Clinically significant improvement in adherence was detected. No significant changes on the psychosocial outcome measures at follow‐up were observed. This study demonstrated that an outpatient‐based mentoring program is a safe, feasible, and acceptable option to incorporate within a pediatric liver transplant program with potential for promising application in other transplantation populations as well. These results also suggest that the program may have been associated with meaningful improvement in adherence, although further evaluation is warranted.     

Parents in transition: Experiences of parents of young people with a liver transplant transferring to adult services

Predictors of successful transition from pediatric to adult services include ability to self‐manage and engage with healthcare services. Parents have a key role in healthcare management throughout childhood and adolescence including encouraging development of self‐management skills in their children. Transition to adult services can be challenging for parents and young people, yet parents’ views regarding transition remain largely unexplored. Nine parents of pediatric liver transplant recipients (15.2–25.1 yr) participated in semistructured interviews. Interviews were analyzed using IPA. Analysis revealed three key themes: “emotional impact of transplantation,” “protection vs. independence,” and “ending relationships and changing roles.” Parents expressed the dichotomous nature of the desire to promote independence in their child while still maintaining control and protection, and discussed how changing roles and relationships were difficult to navigate. Parents are important facilitators of young people's development of self‐management skills for successful transfer to adult services. Parents should be supported to move from a “managerial” to a “supervisory” role during transition to help young people engage independently with the healthcare team. Findings support the development of interventions for parents to emphasize their role in transition and guide the transfer of self‐management skills from parent to young person.     

Assessing associations between medication adherence and potentially modifiable psychosocial variables in pediatric kidney transplant recipients and their families

Post-transplant immunosuppressant (IS) medication adherence is essential for long-term graft survival and relatively little is known about psychosocial barriers that interfere with optimum medication adherence in pediatric kidney transplant patients. The objective of this prospective observational cohort study was to assess the impact of modifiable psychosocial variables on medication adherence. Our hypothesis was that parental stress, dysfunctional parent-child interactions and child behavior problems would be associated with poorer medication adherence. Thirteen pediatric kidney transplant patients and their caregivers were enrolled. Transplant recipients who were able to read and caregivers of all the transplant recipients completed behavioral and attitudinal surveys. A subgroup of seven families dispensed their primary IS medication from an electronic monitoring vial (MEMS Smart Cap). For these patients, medication adherence was calculated by computing a ratio of the medication taken divided by the prescribed dose. In addition, for the entire group, serial IS levels were reviewed by two board certified pediatric nephrologists who categorized all 13 transplant recipient families as either 'probably adherent (PA)' or 'possibly non-adherent (PNA)'. Pearson correlation coefficients and independent samples Student t-tests were used to assess the association between medication adherence and psychosocial variables measured by standardized questionnaires. In this study, elevated parental stress, dysfunctional parent-child interactions, and child behavior problems were associated with poorer medication adherence. In addition, we found evidence to support the relationship between subjective dissatisfaction with appearance and poorer medication adherence. These findings suggest that pre-transplant recipient evaluations of risk factors for poor adherence are warranted.