Understanding the pathway between the transplant experience and health-related quality of life outcomes in adolescents

Abstract:  Developments in solid organ transplantation have resulted in improved survival for children with advanced kidney, liver, and heart disease; however, concerns have been raised regarding the quality of life of survivors. This study examined HRQOL in adolescent transplant recipients. We examined the influence of demographic, treatment regimen, and family factors on physical and mental health domains of HRQOL. The current single-center investigation involved 68 solid organ transplant recipients and their parents. All families participated in a structured interview to collect information on demographics, characteristics of the adolescents' disease and treatment regimen, family functioning, and HRQOL for parents and adolescents. Using hierarchical regression analyses, predictive models of physical functioning and mental health outcomes for adolescent transplant recipients were developed for parent-proxy and adolescent self-report. Perceived frequency of medication side-effects and family conflict significantly contributed to adolescent physical functioning and mental health outcomes. Taken together, transplant consequences and family environment significantly impact physical and mental health outcomes in adolescent transplant recipients. Our findings demonstrate the need for pharmacological considerations and psychological interventions to address these areas.     

Prospective comparison of parent and adolescent report of health‐related quality of life in adolescent solid organ transplant recipients

Devine KA, Reed‐Knight B, Simons LE, Mee LL, Blount RL. Prospective comparison of parent and adolescent report of health‐related quality of life in adolescent solid organ transplant recipients.
Pediatr Transplantation 2010: 14:1000–1006. © 2010 John Wiley & Sons A/S. Abstract: This 18‐month prospective investigation sought to examine changes in HRQOL over time for adolescent solid organ transplant recipients. Additionally, this study examined the relationship between adolescent and parent report of HRQOL and compared parent report of HRQOL to published normative data. Forty‐eight adolescent–parent dyads completed the CHQ, a measure of HRQOL, at two time periods. Parent and adolescent reports of HRQOL were stable over time. ICCs between parent and adolescent reports were significant and moderate across most domains of HRQOL, with the exception of family cohesion, physical functioning, and bodily pain. However, mean differences indicated that parents perceived significantly worse self‐esteem and general health perceptions compared to their adolescents. Compared to normative data, parents reported significantly lower HRQOL across several domains, including adolescents’ physical functioning and the emotional impact of their adolescent’s condition on themselves. However, parents also reported higher levels of family cohesion. Results indicate that assessment of HRQOL for transplant recipients should include multiple reporters and that HRQOL as reported by adolescents and parents is generally stable over time without intervention. Further research is needed to understand factors related to differential HRQOL outcomes.     

Sleep quality is associated with psychosocial functioning and health‐related quality of life in pediatric transplant recipients

This study examined patient‐reported sleep quality in a single‐center cross‐sectional sample of adolescents with solid organ transplants and evaluated associations between sleep quality, psychosocial functioning (ie, depression/anxiety symptoms), and HRQOL. Health disparities associated with minority race/ethnicity and socioeconomic variables were also examined. Sixty‐nine adolescents (M = 16.51 years; SD = 1.63) who received a solid organ transplant (kidney: n = 25; liver: n = 24; heart: n = 20) completed self‐report measures of sleep quality, psychosocial functioning, and HRQOL. Adolescent transplant recipients endorsed significantly lower levels of sleep quality (ie, falling asleep) compared with previously published norms of healthy peers (t = ?3.60; P ≤ .001). Higher sleep quality was significantly associated with fewer anxiety and depressive symptoms (r = ?.31 to ?.40), and higher physical and psychosocial HRQOL (r = .33‐.43). Adolescents from minority backgrounds had significantly worse sleep quality compared with non‐Hispanic Whites. Adolescent transplant recipients, particularly those from minority backgrounds, may be at increased risk for experiencing poor sleep quality. Suboptimal sleep is a risk factor for higher levels of anxiety and depressive symptoms, as well as lower levels of physical and psychosocial HRQOL. Sleep is an important modifiable factor that, if improved, may contribute to lower anxiety/depressive symptoms and better HRQOL in adolescent transplant recipients.     

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.     

Practice recommendations for the monitoring of renal function in pediatric non‐renal organ transplant recipients

The management of non‐renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post‐transplantation follow‐up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non‐renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24‐h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non‐renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m².     

Best practices in the pediatric pretransplant psychosocial evaluation

Assessment of psychosocial functioning is an often‐included component of the pretransplant evaluation process. This study reviews several domains of assessment that have been related to post‐transplant outcomes across solid organ transplant populations. These include evaluation of patient and family past adherence, knowledge about the transplantation process, and their neurocognitive, psychological, and family functioning. To date, few comprehensive pretransplant evaluation measures have been standardized for use with children; however, several assessment measures used to evaluate the aforementioned domains are reviewed throughout the study. Additionally, this article discusses some developmental, illness‐specific, and cultural considerations in conducting the psychosocial evaluation. We also discuss ethical issues specific to the pediatric psychosocial evaluation. Recommendations are advanced to promote a comprehensive evaluation that identifies family strengths and risk factors as they begin the transplant journey.     

Pediatric Transplant Rating Instrument – A scale for the pretransplant psychiatric evaluation of pediatric organ transplant recipients

Abstract:  Although the majority of pediatric solid organ transplant centers in the United States employ psychosocial criteria to assess the suitability of potential transplant candidates, there are no standardized pretransplant psychosocial assessment measures. Assessment scales that have been developed were designed for adult transplant recipients and are not suitable for use in the pediatric population. The P-TRI was developed to address this gap in the pediatric pretransplant psychosocial evaluation. It is intended to identify areas of psychosocial vulnerability that may be associated with poor treatment adherence and to facilitate the development of informed and focused psychosocial interventions for pediatric patients before and after transplant surgery. Items on the rating instrument were generated based on a review of the major correlates of treatment adherence in the pediatric population. Data are currently being collected for further reliability and validity analyses.     

Pretransplant patient,parent, and family psychosocial functioning varies by organ type and patient age

The goal of this study was to compare pretransplant patient HRQOL, parent psychological functioning, and the impact of the patient's ongoing illness on the family between organ types (ie, kidney, liver, heart) and age‐groups (ie, children, AYAs). The sample included 80 pediatric patients with end‐stage organ disease who were evaluated for transplantation and their parents. Parents completed self‐ and proxy reports at patients' pretransplant evaluations. Results indicated that patients evaluated for heart transplants consistently had lower HRQOL and their parents had greater psychological distress compared to the kidney and liver groups. Within the heart group, parents and families of children (<12 years old) experienced significantly more distress and impact of the patient's illness on the family compared to those of AYAs (≥12 years old). Pediatric patients awaiting heart transplants, particularly younger children, and their parents and families may have greater psychosocial needs compared to patients awaiting kidney or liver transplants.     

Child and family adjustment following pediatric solid organ transplantation: Factors to consider during the early years post‐transplant

Adjusting to life after transplant can be challenging to pediatric solid organ transplant recipients and their families. In this review, we discuss a number of important factors to consider during the first 2–3 yr after transplant (defined as the “early years”), including transitioning from hospital to home, returning to physical activity, feeding and nutrition, school reentry, potential cognitive effects of transplant, family functioning, and QOL. We highlight steps that providers can take to optimize child and family adjustment during this period.     

New insights into family functioning and quality of life after pediatric liver transplantation

Denny B, Beyerle K, Kienhuis M, Cora A, Gavidia‐Payne S, Hardikar W. New insights into family functioning and quality of life after pediatric liver transplantation. Abstract: Thorough research of the medical aspects of pediatric liver transplantation has given way to recent interest in the impact of the transplantation process on the QOL of recipients and their families. In this cross‐sectional study, we compared the family functioning and QOL of children (n = 30) aged between three and 16 yr (M = 10.10, s.d. = 3.62) who had received a liver transplant in the previous 1–12 yr (M = 5.31, s.d. = 3.44) with non‐transplant children (n = 33), as reported via parent proxy. Results showed that parents of pediatric liver transplant recipients made significantly more adjustments to family routines to accommodate their children, particularly in relation to childcare. Impaired family functioning was also found to be associated with decreased QOL. These preliminary findings of relative deficits in family functioning may inform psychosocial interventions to assist pediatric liver transplant patients and their families. Further investigation beyond a single‐center study incorporating subjective information from pediatric patients and their parents is recommended.     

Subclinical cardiovascular changes in pediatric solid organ transplant recipients: A systematic review and meta‐analysis

CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. cIMT, central pWV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta‐analysis was to investigate the prevalence of subclinical CV changes, as measured by cIMT, pWV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE^® and EMBASE and conducted meta‐analysis for studies that evaluated cIMT, central pWV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean cIMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02–0.07; p < 0.0001) with an estimated pooled prevalence of elevated cIMT of 56.0% (95% CI 17.0–95.0). The one study that assessed pWV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation.     

Pediatric Transplant Rating Instrument - a scale for the pretransplant psychiatric evaluation of pediatric organ transplant recipients.

Although the majority of pediatric solid organ transplant centers in the United States employ psychosocial criteria to assess the suitability of potential transplant candidates, there are no standardized pretransplant psychosocial assessment measures. Assessment scales that have been developed were designed for adult transplant recipients and are not suitable for use in the pediatric population. The P-TRI was developed to address this gap in the pediatric pretransplant psychosocial evaluation. It is intended to identify areas of psychosocial vulnerability that may be associated with poor treatment adherence and to facilitate the development of informed and focused psychosocial interventions for pediatric patients before and after transplant surgery. Items on the rating instrument were generated based on a review of the major correlates of treatment adherence in the pediatric population. Data are currently being collected for further reliability and validity analyses.     

Post‐transplant malignancies in pediatric organ transplant recipients

The majority of cancer diagnoses in pediatric solid organ transplant recipients (SOTRs) are post‐transplantation lymphoproliferative disorders (PTLD) or skin cancers. However, pediatric SOTRs are also at significantly elevated risk for multiple other solid and hematological cancers. The risks of specific cancers vary by transplanted organ, underlying disease, and immunosuppression factors. More than one‐quarter of pediatric SOTRs develop cancer within 30 years of transplantation and their risk of solid cancer is 14 times greater than the general population. Pediatric SOTRs are at significantly higher risk of cancer‐associated death. Improving patient survival among pediatric SOTRs puts them at risk of adult epithelial cancers associated with environmental carcinogenic exposures. Vaccination against oncogenic viruses and avoidance of excessive immunosuppression may reduce the risk of solid cancers following transplantation. Patient and family education regarding photoprotection is an essential component of skin cancer prevention. There is significant variability in cancer screening recommendations for SOTRs and general population approaches are typically not validated for transplant populations. An individualized approach to cancer screening should be developed based on estimated cancer risk, patient life expectancy, and screening test performance.     

Quality of life in pediatric liver transplantation in a single‐center in South America

Sanchez C, Eymann A, De Cunto C, D’Agostino D. Quality of life in pediatric liver transplantation in a single‐center in South America.
Pediatr Transplantation 2010: 14: 332–336. © 2009 John Wiley & Sons A/S. Abstract: HRQOL in children after LT has not been systematically measured in transplant recipients from South American countries. The aim of this study was to determine the HRQOL using a validated measure for children. The CHQOL‐PF50 was completed by the parents of 54 patients after the clinical assessment. Subscale mean scores were compared with both a normal population (n = 274) and a group of chronic illness patients with Juvenile Idiopathic Arthritis (n = 23). Compared with the normal population, LT recipients had lower subscales scores for general health perceptions, role/social emotional, mental health, and parental impact on time. Bodily pain was significantly lower in our study group. Both mean physical and psychosocial summary scores were lower compared to the normal population but similar to the JIA group. Within the LT population, gender, original diagnosis, type of immunosuppression, type of transplant and time elapsed since LT did not significantly influence any of the summary scores. Our study showed LT children’s physical and psycho‐social areas were lower compared with those of the general population. LT children had less limitations due to pain. Family functioning appeared normal.     

Psychological functioning and psychosocial issues in pediatric kidney transplant recipients

Research demonstrates that psychological factors are important for positive transplant outcomes, though there is little literature that synthesizes these factors in a comprehensive model among pediatric kidney transplant patients. This review analyzes psychological and psychosocial factors related to medical outcomes and overall well‐being post‐transplant by utilizing the PPPHM and referencing the existing literature on risk and resilience. Pediatric kidney transplant recipients are more susceptible to mental health concerns such as depression, anxiety, and ADHD, as well as developmental and neurocognitive delays, compared to healthy peers. Complex medical care and psychosocial needs for patients have implications for family functioning, parental and sibling mental health, and youth readiness to transition to adult care. It is important to carefully monitor patient functioning with empirically validated tools and to intervene in a multidisciplinary setting as early as possible to identify patients at risk and reduce potential negative impact. Psychologists are uniquely trained to assess and address these issues and are a valuable component of multidisciplinary, culturally competent care. While research in this expansive field is improving, more data are needed to establish gold standard approaches to mental health and psychosocial care in this population.     

Promoting cardiovascular health post‐transplant through early diagnosis and adequate management of hypertension and dyslipidemia

Despite correction of underlying solid organ failure by transplantation, pediatric transplant recipients still have increased mortality rates compared to the general pediatric population, in part due to increased cardiovascular risk. In particular, pediatric kidney and non‐kidney transplant recipients with chronic kidney disease have significant cardiovascular risk that worsens with declining kidney function. Biomarkers associated with future cardiovascular risk such as casual and ambulatory hypertension, dyslipidemia, vascular stiffness and calcification, and left ventricular hypertrophy can be detected throughout the post‐transplant period and in patients with stable kidney function. Among these, hypertension and dyslipidemia are two potentially modifiable cardiovascular risk factors that are highly prevalent in kidney and non‐kidney pediatric transplant recipients. Standardized approaches to appropriate BP measurement and lipid monitoring are needed to detect and address these risk factors in a timely fashion. To achieve sustained improvement in cardiovascular health, clinicians should partner with patients and their caregivers to address these and other risk factors with a combined approach that integrates pharmacologic with non‐pharmacologic approaches. This review outlines the scope and impact of hypertension and dyslipidemia in pediatric transplant recipients, with a particular focus on pediatric kidney transplantation given the high burden of chronic kidney disease‐associated cardiovascular risk. We also review the current published guidelines for monitoring and managing abnormalities in blood pressure and lipids, highlighting the important role of therapeutic lifestyle changes in concert with antihypertensive and lipid‐lowering medications.     

A systematic review of parent and family functioning in pediatric solid organ transplant populations

The process of pediatric solid organ transplantation (SOT) places new and increased stressors on patients and family members. Measures of family functioning may predict psychological and health outcomes for pediatric patients and their families, and provide opportunity for targeted intervention. This systematic review investigated parent and family functioning and factors associated with poorer functioning in the pediatric SOT population. Thirty‐seven studies were identified and reviewed. Studies featured a range of organ populations (eg, heart, liver, kidney, lung, intestine) at various stages in the transplant process. Findings highlighted that parents of pediatric SOT populations commonly report increased stress and mental health symptoms, including posttraumatic stress disorder. Pediatric SOT is also associated with increased family stress and burden throughout the transplant process. Measures of parent and family functioning were associated with several important health‐related factors, such as medication adherence, readiness for discharge, and number of hospitalizations. Overall, findings suggest that family stress and burden persists post‐transplant, and parent and family functioning is associated with health‐related factors in SOT, highlighting family‐level functioning as an important target for future intervention.     

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.     

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

Limbers CA, Neighbors K, Martz K, Bucuvalas JC, Webb T, Varni JW, Alonso EM, on behalf of the Studies of Pediatric Liver Transplantation (SPLIT) Functional Outcomes Group (FOG). Health‐related quality of life in pediatric liver transplant recipients compared with other chronic disease groups.
Pediatr Transplantation 2011: 15: 245–253. © 2010 John Wiley & Sons A/S. Abstract: 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.