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.     

Assessment of transition readiness skills and adherence in pediatric liver transplant recipients

Fredericks EM, Dore‐Stites D, Well A, Magee JC, Freed GL, Shieck V, Lopez MJ. Assessment of transition readiness skills and adherence in pediatric liver transplant recipients.
Pediatr Transplantation 2010: 14:944–953. © 2010 John Wiley & Sons A/S. Abstract: To examine transition readiness, adherence, and health outcomes in pediatric liver transplant recipients using a clinically administered screening measure. Seventy‐one pediatric liver transplant recipients (11–20 yr) and 58 parents completed a clinic‐based TRS measuring perceived and demonstrated self‐management skills, AoR for health‐related tasks, regimen knowledge, and psychosocial adjustment. Adherence was measured using s.d. of immunosuppressants, proportion of immunosuppressant blood levels out of target range, and clinic attendance. Health outcomes included liver test panels, biopsies, rejection episodes, and hospitalizations. Results indicate that all domains of transition readiness, with the exception of demonstrated skills, and non‐adherence were positively correlated with age. Proportion of immunosuppressant blood levels below target range was positively correlated with self‐management skills and increased responsibility for medication tasks. Parent regimen knowledge was associated with clinic attendance. Health outcomes were significantly related to medication non‐adherence, but not to transition readiness domains. Medication adherence is considered to be a key factor in the transition from pediatric to adult‐centered transplant care. Non‐adherence is associated with an increased risk for medical complications and is potentially modifiable. Interventions to promote self‐management skills and adherence should be an essential component of transition planning.     

Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010

Perito ER, Glidden D, Roberts JP, Rosenthal P. Overweight and obesity in pediatric liver transplant recipients: Prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987–2010.
Pediatr Transplantation 2012: 16: 41–49. © 2011 John Wiley & Sons A/S. Abstract: Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post‐transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987–2010 in children 6 months–20 yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6–24 months at transplant, 14% were overweight. Of 4658 subjects 2–20 yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10 yr after transplant. The prevalence of post‐transplant obesity remained high in long‐term follow‐up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post‐transplant overweight/obesity. To optimize long‐term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important.     

Adherence and medical outcomes in pediatric liver transplant recipients who transition to adult services

Non-adherence to medications is associated with poor medical outcomes in adolescent transplant recipients. It is unclear whether non-adherence is further compromised when transplant recipients transition to the adult health care system. The purpose of the present study was to examine whether adherence changes during transition. We reviewed the medical records of 14 recently transitioned patients and compared their adherence and corresponding medical outcomes before and after transition. These outcomes were also compared with two cohorts of patients receiving care solely in pediatric or adult services. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, was examined for all patients. We found that adherence to tacrolimus significantly decreased after transition. After transitioning, patients furthermore exhibited poorer adherence than patients in the other two cohorts did over time. This small retrospective study suggests that the period of transition from pediatric to adult transplant clinics is a vulnerable one. Larger, prospective investigations of the transition process are necessary before recommendations are made regarding interventions.     

Multicenter data to improve health for pediatric renal transplant recipients in North America: Complementary approaches of NAPRTCS and IROC

Kidney transplantation increases life expectancy and improves quality of life for children with end‐stage kidney disease, yet sequelae of transplantation and treatment make it difficult for transplant recipients to enjoy health and quality of life similar to their healthy peers. The NAPRTCS network was among the first to use multicenter data to inform improvements in care and outcomes for children with a kidney transplant through observational research. Now, with new technologies and unprecedented access to data, it is possible to create learning health systems as envisioned by the US National Academy of Sciences to seamlessly integrate research and continuous improvement of clinical care. In this review, we present two pre‐eminent North American networks focused on using multicenter data to drive improved care and outcomes for children with a kidney transplant. Whereas, for the past 30 years NAPRTCS has focused on discovery of best practices through observational research and clinical trials, the Improving Renal Outcomes Collaborative, established in 2016, engages patients, families, clinicians, and researchers in redesigning the healthcare delivery system to enable practice change and continuous improvement of health outcomes. We discuss the history and past contributions of these networks, as well as current activities, barriers, and potential future solutions to more fully realize the vision of a true learning health system for pediatric kidney transplant recipients.     

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.     

Survey of primary care pediatricians on the transition and transfer of adolescents to adult health care

The transition and transfer from pediatrics to adult health care of youth with and without special health care needs has become a focus of professional organizations, health care insurers, national policy makers, and providers. To understand transition and transfer at a primary care practice level, all primary care pediatricians in Rhode Island were surveyed. Responses were received from 103 of 169 (60.9%) practicing pediatricians. Few responders had practice policies on transfer. Most reported that transition should begin later than recommended. Few practices communicated with adult providers at transfer. Most reported that health insurers were of little help in transfer. Many pediatric practices had young adults after age 22 and many with special needs. Responders reported adolescents left their practices by 1 of 6 methods. The survey indicates the need for further study of transition and transfer and the need for additional training and education if transfers are to be successful.     

Surgeon crossover between pediatric and adult centers is associated with decreased rate of loss to follow‐up among adolescent renal transplantation recipients

The risk of adverse outcomes for pediatric renal transplant patients is highest during the transition from pediatric to adult care. While there have been many studies focus on graft failure and death, loss to follow‐up likely plays a large role in patient outcomes. We hypothesize patients are lost to follow‐up during this transition period and that patients transplanted at pediatric centers with a closely affiliated adult center (AFFs) are less likely to suffer from fragmentation of care and become lost to follow‐up. AFFs were defined as those pediatric centers whose transplant surgeons were also on staff at an adult center and were identified using center websites. We included patients undergoing renal transplantation at <=18 years of age and had data for the entire transition period on the Scientific Registry of Transplant Recipients (n = 6,762, 92.3% in 95 AFFs). 32% of patients were lost to follow‐up. On regression, patients transplanted at AFF were 33% less likely to be lost to follow‐up compared with those from non‐AFF (OR 0.67 CI 0.54‐0.82, P < 0.01). The proportion of patients lost to follow‐up during the transition period is remarkably high, but lower among recipients transplanted at AFFs. Poor follow‐up may be mitigated by improving integration of care.     

The use of everolimus in pediatric liver transplant recipients: first experience in a single center

The role of mTOR inhibitors, such as EVL, has not been established for pediatric liver transplant recipients up to now, although data from adult solid organ graft transplantation are very promising. Major complications following pediatric liver transplantation in the long-term course include chronic graft rejection and CNI-derived nephrotoxicity. The purpose of our study was to report first results using EVL as a rescue therapy in pediatric liver transplant recipients for the following indications: chronic graft dysfunction n=12, suspected CNI toxicity n=3, hepatoblastoma n=2, and recurrence of primary sclerosing cholangitis post-Ltx n=1. Four patients with chronic graft dysfunction developed completely normal liver function tests using EVL, six patients showed partial improvement, and two patients did not respond at all. One patient with CNI-induced nephropathy showed a slightly improved GFR. Both patients with hepatoblastoma did not develop any metastasis post-Ltx. First experience with EVL in pediatric liver transplant recipients shows promising results in patients with chronic graft failure when standard immunosuppression has failed. The future role of EVL in immunosuppressive protocols for children post-Ltx has to be proven by controlled clinical trials.     

Transitioning care of the pediatric recipient to adult caregivers

The development of transitional care is one of the major challenges for the twenty-first century as the survival rates and medical outcomes for child and adolescent recipients of solid organ transplants continue to improve. Such developments must include pediatric and adult care providers and require training of professionals in both arenas. Transition is a process in which the transfer to adult care is only one event within that process. The key elements of transition for pediatric recipients are discussed, and the importance of a coordinated, structured, multidisciplinary approach involving the adolescents themselves is highlighted.     

Transfer from pediatric to adult health care: effects on diabetes outcomes

The transfer from pediatric to adult diabetes health care for emerging adults with type 1 diabetes (T1D) has received increasing attention in the literature. This review analyzes the effect of this health care transfer on the outcomes of diabetes care visit attendance, glycemic control, and acute diabetes‐related complications, and assesses the methodological strength of the studies reporting observational and interventional data. Observational studies, often limited by incomplete data, report a decline in diabetes care visits but an improvement or no change in hemoglobin A1c (HbA1c) after transfer to adult care. Results from studies reporting a transition intervention are restricted by lack of appropriate control groups and the collection of data both before and after transfer of care. Very few methodologically strong studies are available to guide clinicians with the transition from pediatric to adult care, and these shortcomings should be addressed in future studies designed to facilitate and improve the care of emerging adults with T1D.     

The effect of transfer to adult transplant care on kidney function and immunosuppressant drug level variability in pediatric kidney transplant recipients

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non‐adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single‐center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre‐ and post‐transfer was performed via a linear mixed‐effects model. CV TAC was calculated in transplant recipients with TAC data pre‐ and post‐transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre‐ and post‐transfer demonstrated a decrease in the rate of eGFR decline post‐transfer from 8.0 mL/min/1.73 m² per year to 2.1 mL/min/1.73 m² per year, an ~80% decrease in eGFR decline post‐transfer (P = 0.01). Twenty‐four subjects had CV TAC data pre‐ and post‐transfer of care. Pretransfer CV TAC for subjects with allograft loss post‐transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post‐transfer.     

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.     

The hematopoietic stem cell number in the peripheral blood of pediatric recipients correlates with the outcome after living donor liver transplantation

It has been proposed that circulating HSCs play a role in graft survival after liver transplantation. The aim was to analyze the relationship between the number of HSCs before and after LDLT and liver function, immune biomarkers, and clinical outcomes in pediatric patients. We studied 15 pairs of adult healthy liver donors and pediatric recipients with ESLD. The CD34/CD45+ cell number was measured in the blood via flow cytometry, and plasma levels of immune biomarkers – via ELISA. CD34/CD45+ cell number in the recipients decreased within the first week after LDLT. The cell number before LDLT was negatively correlated with the plasma levels of CRP and the development of graft dysfunction in the early post‐transplant period. After LDLT, the CD34/CD45+ cell number was positively correlated with the pretransplant plasma level of sCD40L, a T‐cell activation marker. In adult liver donors, the cell number did not change within the first week after liver resection and was lower than in pediatric recipients. The results suggest that in pediatric recipients, the HSC number may be associated with graft function and could be regarded as a potential predictor of the clinical outcome after LDLT.     

Cost‐efficient screening for BK virus in pediatric kidney transplantation: A single‐center experience and review of the literature

Laskin BL and Goebel J. Cost‐efficient screening for BK virus in pediatric kidney transplantation: A single‐center experience and review of the literature.
Pediatr Transplantation 2010: 14:589–595. © 2010 John Wiley & Sons A/S. Abstract: BKVNP is an increasingly recognized cause of graft dysfunction and loss in kidney transplant recipients. Protocols for BKV screening and for the diagnosis of BKVNP are still evolving. PCR‐based BKV detection became available at our institution in 2007, when we began using it according to published guidelines. We subsequently reviewed our experience with urine and plasma BKV PCR testing in our pediatric kidney transplant recipient population. We found rates of viruria, viremia, and BKVNP that were similar to the published literature. We also conducted a cost analysis suggesting that urine PCR testing, as used by us, is not cost efficient in the detection of BKV. We conclude that plasma only‐based PCR testing for BKV may be sufficient in most clinical settings.     

Barriers to ideal outcomes after pediatric liver transplantation

Long‐term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of “surviving and thriving” with long‐term allograft health, freedom of complications from long‐term immunosuppression, self‐reported well‐being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra‐operative, early‐, medium‐, and long‐term post‐transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.     

Methodologic issues in the conduct and interpretation of pediatric effectiveness research.

Effectiveness research represents a number of methodologic challenges not shared with randomized, controlled clinical trials. This practice-based research attempts to translate clinical practices to a wide variety of different practice settings and situations and to diverse patient subgroups. However, because study designs most often used in the conduct of effectiveness research limit the ability to establish firm causal links between medical care and outcomes, it is important to address key methodologic features to generate sound, useable findings. Such features include selection of appropriate outcome measures (with a priori hypotheses linking care to the outcomes chosen), specification of appropriate primary sampling unit, specification of unit of analysis, establishment of appropriate comparison groups, and case-mix adjustment.Conduct of this type of research in pediatrics presents a number of unique methodologic concerns that either do not apply in adult medicine or are particularly acute in pediatrics. To alert policy makers and funders to the unique aspects of pediatric health services research and to provide guidance for the conduct and interpretation of pediatric effectiveness studies, we have organized and described the methodologic issues associated with the specific type of pediatric care under study (eg, specific disease-prevention, "bundled" care for chronic disease, care for problems with social etiologies, etc). We conclude with a summary of the methodologic steps that are critical to the conduct of sound effectiveness research in pediatrics.     

Successful Integration of Pediatrics Into State Health Care Reform Efforts

Health care reform in Vermont promotes patient-centered medical homes (PCMH) and multi-disciplinary community health teams to support population health. This qualitative study describes the expansion of Vermont's health care reform efforts, initially focused on adult primary care, to pediatrics through interviews with project managers and facilitators, CHT members, pediatric practitioners and care coordinators, and community-based providers. Analyses used grounded theory, identifying themes confirmed by repeat occurrence across respondents. Respondents believed that PCMH recognition and financial and community supports would improve care for pediatric patients and families. Respondents shared three main challenges with health care reform efforts: achieving PCMH recognition, adapting community health teams for pediatric patients and families, and defining roles for care coordinators. For health care reform efforts to support pediatric patients and be family-centered, states may need additional resources to understand how pediatric and adult primary care differ and how best to support pediatrics during health care reform efforts.