Allied health and nursing practices in pediatric solid organ transplantation: An international survey.

INTRODUCTION: With improved survival in pediatric solid organ transplantation (SOT) care has focused on optimizing functional, developmental, and psychosocial outcomes, roles often supported by Allied Health and Nursing professionals (AHNP). However, there is a scarcity of research examining frameworks of clinical practice. METHODS: The International Pediatric Transplant Association AHNP Committee developed and disseminated an online survey to transplant centers as a quality improvement project to explore AHNP practice issues. Participant responses were characterized using descriptive statistics, and free-text comments were thematically analyzed. Responses were compared across professional groups; Group 1: Advanced Practice Providers, Group 2: Nursing, Group 3: Allied Health. RESULTS: The survey was completed by 119 AHNP from across the globe, with responses predominantly (78%) from North America. Half of respondents had been working in pediatric transplant for 11+ years. Two-thirds of respondents were formally funded to provide transplant care; however, of these not funded, over half (57%) were allied health, compared to just 6% of advance practice providers. Advanced practice/nursing groups typically provided care to one organ program, with allied health providing care for multiple organ programs. Resource constraints were barriers to practice across all groups and countries. CONCLUSION: In this preliminary survey exploring AHNP roles, professionals provided a range of specialized clinical care. Challenges to practice were funding and breadth of care, highlighting the need for additional resources, alongside the development of clinical practice guidelines for defining, and supporting the role of AHNP within pediatric SOT. Professional organizations, such as IPTA, can offer professional advocacy.

Branched-chain α-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes.

Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing.

Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: Expanding the donor pool for live donor liver transplantation.

AIM/BACKGROUND: Domino liver transplantation (DLT) using liver allografts from patients with metabolic disorders enhances organ utilization. Short- and long-term course and outcome of these patients can impact the decision to offer this procedure to patients, especially those with diseases that can potentially be cured with liver transplant. We reviewed the outcomes of DLT from maple syrup urine disease (MSUD) patients in our large academic pediatric and adult transplant program. METHODS: All patients receiving DLT were analyzed retrospectively with a minimum of one-year follow-up period for patient and donor characteristics, early and late postoperative complications and patient and graft survival with their MSUD donors in terms of age, weight, MELD/PELD scores, cold ischemia time, postoperative leucine levels, and peak ALT (alanine aminotransferase) levels during the first 48 postoperative hours. RESULTS: Between 2006 and May 2019, 21 patients underwent domino liver transplantation with live donor allografts from MSUD patients. Four patients transplanted for different metabolic diseases are focus of a separate report. Seventeen patients with minimum one-year follow-up period are reported herein. The indications were primary sclerosing cholangitis (PSC, n = 4), congenital hepatic fibrosis (CHF, n = 2), alpha-1 antitrypsin deficiency (A-1 ATD, n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), cystic fibrosis (n = 1), primary biliary cirrhosis (PBC, n = 1), neonatal hepatitis (n = 1), embryonal sarcoma (n = 1), Caroli disease (n = 1), hepatocellular carcinoma (HCC, n = 1), and chronic rejection after liver transplantations for PSC (n = 1). All patients and grafts survived at median follow-up of 6.4 years (range 1.2-12.9 years). Median domino recipient age was 16.2 years (range 0.6-64.6 years) and median MSUD recipient age was 17.6 years (range 4.8-32.1 years). There were no vascular complications during the early postoperative period, one patient had portal vein thrombosis 3 years after DLT and a meso-Rex bypass was successfully performed. Small for size syndrome (SFSS) occurred in reduced left lobe DLT recipient and was managed successfully with conservative management. Biliary stricture developed in 2 patients and was resolved by stenting. Comparison between DLT and MSUD recipients' peak postoperative ALT results and PELD/MELD scores showed lower levels in DLT group (P-value <.05). CONCLUSIONS: Patient and graft survival in DLT from MSUD donors was excellent at short- and long-term follow-up. Metabolic functions have been normal in all recipients on a normal unrestricted protein diet. Ischemia preservation injury based on peak ALT was significantly decreased in DLT recipients. Domino transplantation from pediatric and adult recipients with selected metabolic diseases should be increasingly considered as an excellent option and alternative to deceased donor transplantation, thereby expanding the living donor pool. This, to date, is the largest world experience in DLT utilizing livers from patients with MSUD.

Pediatric heart transplantation at adult-specialty centers in the United States: A multicenter registry analysis.

Recent Organ Procurement and Transplantation Network bylaw revisions mandate that US transplant programs have an "approved pediatric component" in order to perform heart transplantation (HT) in patients <18 years old. The impact of this change on adolescents, a group known to be at high risk for graft loss and nonadherence, is unknown. We studied all US primary pediatric (age <18 years) HT from 2000 to 2015 to compare graft survival between centers organized mainly for adult versus pediatric care. Centers were designated as pediatric- or adult-specialty care according to the ratio of pediatric:adult HT performed and minimum age of HT (pediatric-specialty defined as ratio>0.7; adult-specialty ratio<0.05 and minimum age >8 years). In propensity score-matched cohorts, we observed no difference in graft loss by center type (median survival: adult 12.4 years vs pediatric 9.2 years, P = .174). Compared to the matched pediatric cohort, adult-specialty center recipients lived closer to their transplant center (31 vs 45 miles, P = .012), and trended toward fewer out-of-state transplants (15 vs 25%, P = .082). Our data suggest that select adolescents can achieve similar midterm graft survival at centers organized primarily for adult HT care. Regardless of post-HT setting, the development of care models that demonstrably improve adherence may be of greatest benefit to improving survival of this high-risk population.

Development and field testing of Teen Pocket PATH(®), a mobile health application to improve medication adherence in adolescent solid organ recipients.

Applying principles of user-centered design, we iteratively developed and tested the prototype of TPP, an mHealth application to promote medication adherence and enhance communication about medication management between adolescents and primary caregivers. A purposive sample of seven adolescent solid organ transplant recipients who were ≥ one yr post-transplant and their primary caregivers participated. Participants completed up to three face-to-face laboratory usability sessions, a 6-week field test, and a debriefing session. Primary caregivers participated in an additional usability telephone session. Participants completed usability and satisfaction measures. Sample included liver (n = 4), heart (n = 2), and lung (n = 1) recipients aged 11-18 yr (57% were female, 86% were Caucasian), and nine primary caregivers aged 42-61 yr (88.9% were parents, 88% were female, 88% were Caucasian). Ninety percent of the adolescents endorsed the graphs or logs of missed/late medication dosing as useful and 100% endorsed the remaining features (e.g., medication list, dose time reminders/warnings) as useful. All adolescents expressed interest in using TPP for monitoring medications and satisfaction with the automatic messaging between adolescent and caregiver versions of the application. Adolescents unanimously found TPP easy to use. TPP shows promise as an mHealth adherence tool.

Quality of recipient-caregiver relationship and psychological distress are correlates of self-care agency after lung transplantation.

Self-care behaviors are crucial for following the complex regimen after lung transplantation, yet little is known about recipients' levels of self-care agency (the capability and willingness to engage in self-care behaviors) and its correlates. We examined levels of self-care agency and recipient characteristics (socio-demographics, psychological distress, quality of relationship with primary lay caregiver, and health locus of control) in 111 recipients. Based on Perceived Self-Care Agency scores, recipients were assigned to either the low- or high-self-care agency comparison group. Characteristics were compared between groups to identify characteristics likely to be associated with lower-self-care agency. Mean (SD) score for self-care agency (scale range, 53-265) was 223.02 (22.46). Recipients with lowest-self-care agency scores reported significantly poorer quality of caregiver relationships (p < 0.001) and greater psychological distress (p < 0.001). After controlling for psychological distress, the quality of the recipient-caregiver relationship remained significantly associated with self-care agency. Every one-point decrease in the quality of caregiver relationship increased the risk of low-self-care agency by 12%. Recipients with poorer caregiver relationships and greater psychological distress may need additional support to perform the self-care behaviors expected after lung transplantation.

Adaptive functioning and its correlates after intestine and liver transplantation.

In this cross-sectional study, we compared levels of adaptive functioning and examined potential correlates of adaptive functioning in 18 pediatric intestine (ITX) and 22 liver (LTX) recipients transplanted between June 2003 and March 2009. Family caregivers completed the ABAS-II scale and provided socio-demographic information regarding recipients' age at transplantation, gender, ethnicity, time since transplantation, and caregivers' role, ethnicity, education, and family income. Overall adaptive functioning and all three adaptive functioning subdomain scores were significantly lower in ITX patients compared with LTX patients (p ≤ 0.04) and compared with the general population normative mean (p ≤ 0.003). Significant correlates of adaptive functioning after abdominal transplant included type of transplant procedure (r = -0.4, p = 0.02), gender (r = 0.4, p = 0.01), and educational level of caregiver (r = 0.5, p = 0.003) and together explained 45% of the variance in overall adaptive functioning. Findings provide new information regarding everyday functioning outcomes of ITX patients, add to existing data regarding non-medical outcomes for LTX patients, and highlight the need for ongoing monitoring and intervention following transplantation to enhance outcomes.

Medical adherence in pediatric organ transplantation: what are the next steps?

PURPOSE OF REVIEW: Adherence within pediatric transplantation has gained importance as the complexities of long-term medical management of these patients are identified and knowledge regarding the negative consequences of nonadherence accumulates. We review recent findings to highlight gaps in the literature and make suggestions for future directions. RECENT FINDINGS: Most research has focused on medication nonadherence, and a recent meta-analysis indicates that nonadherence is more prevalent in adolescent transplant recipients than in younger children. Nonadherence to other areas of the regimen (e.g. clinic attendance) may be even more common than medication nonadherence. However, work to date is based primarily on kidney and liver pediatric transplant patients, with a paucity of research on heart, lung and intestinal recipients. Risk factors for nonadherence after pediatric transplantation include poor family and child functioning. Intervention research remains rare. Challenges include the need for clearer definitions of what constitutes clinically significant nonadherence, longitudinal and prospective assessment of a wider range of potential risk factors, and the development and evaluation of interventions to treat or prevent nonadherence. SUMMARY: Adherence research in pediatric transplantation is in its infancy. Significant opportunities exist to advance the field and create standards for effective identification, measurement, and treatment of nonadherence.

Domino liver transplantation for select metabolic disorders: Expanding the living donor pool.

Domino liver transplantation (DLT) involves transplanting liver from a patient with metabolic disease into a patient with end-stage liver disease with the expectation that the recipient will not develop the metabolic syndrome or the recurrent syndrome will have minimal affect. The domino donor gets a deceased donor or a segment of live-donor liver through the deceased donor organ allocation system. Waitlist mortality for the domino recipient exceeds morbidity associated with getting the donor disease. Between 2015 and 2017, four patients with three metabolic disorders at UPMC Children's Hospital of Pittsburgh underwent DLT with domino allografts from maple syrup urine disease (MSUD) patients. These included patients with propionic acidemia (PA) (n = 1), Crigler-Najjar (CN) syndrome type-1 (n = 2), and carbamoyl phosphate synthetase deficiency (CPSD) (n = 1). Mean follow-up was 1.6 years (range 1.1-2.1 years). Total bilirubin levels normalized postoperatively in both CN patients and they maintain normal allograft function. The PA patient had normal to minimal elevations of isoleucine and leucine, and no other abnormalities on low protein diet supplemented with a low methionine and valine free formula. No metabolic crises have occurred. The patient with CPSD takes normal baby food. No elevation in ammonia levels have been observed in any of the patients. DLT for a select group of metabolic diseases alleviated the recipients of their metabolic defect with minimal evidence of transferrable-branched chain amino acid elevations or clinical MSUD despite increased protein intake. DLT using allografts with MSUD expands the live donor liver pool and should be considered for select metabolic diseases that may have a different enzymatic deficiency.

Depression and Anxiety as Risk Factors for Morbidity and Mortality After Organ Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression and anxiety are common mental health problems in transplant populations. There is mixed evidence concerning whether they increase morbidity and mortality risks after transplantation. If such associations exist, additional risk reduction strategies may be needed. METHODS: Four bibliographic databases were searched from 1981 through September 2014 for studies prospectively examining whether depression or anxiety (determined with diagnostic evaluations or standardized symptom scales) affected risk for posttransplant mortality, graft loss, acute graft rejection, chronic rejection, cancer, infection, and rehospitalization. RESULTS: Twenty-seven studies (10 heart, total n = 1738; 6 liver, n = 1063; 5 kidney, n = 49515; 4 lung, n = 584; 1 pancreas, n = 80; 1 mixed recipient sample, n = 205) were identified. In each, depression and/or anxiety were typically measured before or early after transplantation. Follow-up for outcomes was a median of 5.8 years (range, 0.50-18.0). Depression increased the relative risk (RR) of mortality by 65% (RR, 1.65; 95% confidence interval [95% CI], 1.34-2.05; 20 studies). Meta-regression indicated that risk was stronger in studies that did (vs did not) control for potential confounders (P = .032). Risk was unaffected by type of transplant or other study characteristics. Depression increased death-censored graft loss risk (RR, 1.65; 95% CI, 1.21-2.26, 3 studies). Depression was not associated with other morbidities (each morbidity was assessed in 1-4 studies). Anxiety did not significantly increase mortality risk (RR, 1.39; 95% CI, 0.85-2.27, 6 studies) or morbidity risks (assessed in single studies). CONCLUSIONS: Depression increases risk for posttransplant mortality. Few studies considered morbidities; the depression-graft loss association suggests that linkages with morbidities deserve greater attention. Depression screening and treatment may be warranted, although whether these activities would reduce posttransplant mortality requires study.

Meta-analysis of medical regimen adherence outcomes in pediatric solid organ transplantation.

BACKGROUND: Adherence to the medical regimen after pediatric organ transplantation is important for maximizing good clinical outcomes. However, the literature provides inconsistent evidence regarding prevalence and risk factors for nonadherence posttransplant. METHODS: A total of 61 studies (30 kidney, 18 liver, 8 heart, 2 lung/heart-lung, and 3 with mixed recipient samples) were included in a meta-analysis. Average rates of nonadherence to six areas of the regimen, and correlations of potential risk factors with nonadherence, were calculated. RESULTS: Across all types of transplantation, nonadherence to clinic appointments and tests was most prevalent, at 12.9 cases per 100 patients per year (PPY). The immunosuppression nonadherence rate was six cases per 100 PPY. Nonadherence to substance use restrictions, diet, exercise, and other healthcare requirements ranged from 0.6 to 8 cases per 100 PPY. Only the rate of nonadherence to clinic appointments and tests varied by transplant type: heart recipients had the lowest rate (4.6 cases per 100 PPY vs. 12.7-18.8 cases per 100 PPY in other recipients). Older age of the child, family functioning (greater parental distress and lower family cohesion), and the child's psychological status (poorer behavioral functioning and greater distress) were among the psychosocial characteristics significantly correlated with poorer adherence. These correlations were small to modest in size (r=0.12-0.18). CONCLUSIONS: These nonadherence rates provide benchmarks for clinicians to use to estimate patient risk. The identified psychosocial correlates of nonadherence are potential targets for intervention. Future studies should focus on improving the prediction of nonadherence risk and on testing interventions to reduce risk.

The challenges of using medication event monitoring technology with pediatric transplant patients.

This study investigated the advantages and challenges of using Medication Electronic Monitoring System (MEMS) technology to examine adherence among pediatric kidney transplant patients. Twenty-nine patients participated in the study, with a mean age of 14.03 yr (SD = 3.34, range 8-19 yr). Patients were given a MEMS bottle and cap to be used with their primary immunosuppressant medication over a three-month period. Issues related to study eligibility, recruitment, and participant maintenance were recorded. Patients completed the Debriefing Form regarding their experiences with the MEMS. Many younger patients were on liquid medications affecting the feasibility of this technology across ages. Acceptance of this technology proved difficult, as many patients either declined upfront or dropped out because they did not want to use the MEMS. Of the final sample, 41% found transferring medication into the MEMS bottle difficult and 27.2% reported that the MEMS was a burden and/or difficult to transport. Another 22% of the patients reported that using the MEMS changed their routine, and 10.2% worried about missing their medications. Pediatric transplant centers should be cautious about solely relying on MEMS to examine adherence until more research is conducted on the feasibility, acceptance, and utility of this technology.