Diana A. Shellmer

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.

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.

Race and ethnicity in decisions about unrelated hematopoietic stem cell donation

Large international registries of potential unrelated hematopoietic stem cell (HSC) donors, including the National Marrow Donor program (NMDP), continue to face difficulties finding matched donors for racial/ethnic minorities. One reason, in addition to the generally less common HLA types among minority patients, is the much higher registry attrition rate of racial/ethnic minorities compared with whites. Reasons for the higher attrition among minority potential donors remain unexplained. The goal of our cross-sectional telephone interview study was to generate a diverse sample of potential HSC donors who have preliminarily matched a patient and to identify factors associated with race/ethnicity and with the decision to continue toward potential donation or to opt out of the registry. Multiple culturally related, psychosocial, and donation-related factors were associated both with race/ethnic group membership and attrition from the registry. The most consistent factor associated with opting out of the registry across all race/ethnic groups was ambivalence about donation: doubts and worries, feeling unsure about donation, wishing someone else would donate in ones place. Our findings suggest that universal donor recruitment and management approaches based on reducing donation-related ambivalence and tailored messages and strategies for each of the individual race/ethnic groups are important.

Cognitive and adaptive functioning after liver transplantation for maple syrup urine disease: a case series.

Shellmer DA, DeVito Dabbs A, Dew MA, Noll RB, Feldman H, Strauss KA, Morton DH, Vockley J, Mazariegos GV. Cognitive and adaptive functioning after liver transplantation for maple syrup urine disease: A case series.
Pediatr Transplantation 2011: 15:58–64.

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

Purpose of reviewAdherence 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 findingsMost 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. SummaryAdherence 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.

The start of the transplant journey: Referral for pediatric solid organ transplantation

The focus of the majority of the psychosocial transplant literature is on post‐transplant outcomes, but the transplant journey starts much earlier than this, at the point when transplantation is first considered and a referral for transplant evaluation is made. In this review, we cover information regarding the meaning of the referral process for solid organ transplantation. We discuss various factors of the referral for transplantation including the impact of referral on the pediatric patient and the family, potential expectations and misconceptions held by pediatric patients and parents, the role of health literacy, decision‐making factors, and the informational needs of pediatric patients and parents. We elucidate steps that providers can take to enhance transplant referral and provide suggestions for much needed research within this area.

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.

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.

Predicting non‐adherence: Striking the right balance

The importance of adherence post-transplantation, and the limited amount of data available to help medical providers determine whether specific patients are at increased risk of being nonadherent to medications, is the reported impetus for the paper by Connelly et al. (1) In their exploratory single center study, Connelly and colleagues retrospectively examined the records of 175 pediatric kidney recipients in an attempt to identify factors that predict non-adherence to medication after transplant. Connelly and colleagues define medication non-adherence as “. . .provider documentation appearing in the medical record of a belief of non-adherence based on patient/caregiver interview, laboratory data, patient admission of non-adherence, or documented interruptions in the plan of care which the provider indicated as non-adherence.” Factors identified by the authors as being of the greatest importance, and as being potentially associated with medication non-adherence, were extracted from the medical record. Connelly and colleagues report that when fit into a model, race, gender, age at transplant, living in an urban area, distance to hospital, and involvement in legal issues had the greatest association with medication non-adherence. The authors also included CMV status, primary disease recurrence, and financial issues into the model. When these nine risk factors were fit into the model, it predicted 30% of the variability in “the development of medication non-adherence” post-transplantation. The model is described as having strong “predicative” value (69% positive predicative value and 81% negative predicative value), and Connelly and colleagues encouraged medical providers to utilize the model to estimate the risk of non-adherence. Of note, laboratory data on tacrolimus trough levels, a potentially objective way of assessing non-adherence, were not found to be associated with adherence, as trough levels were not statistically different in the participants classified as adherent versus those classified as non-adherent. The authors’ attempt to develop a model that would assist clinicians in determining the potential for medication non-adherence is a step toward trying to standardize the assessment of risk. Connelly and colleagues suggest that implementation of the model could help providers focus their efforts and conceivably change the approach they take with certain “at risk” patient populations. However, implementing the use of this model to predict non-adherence without exploring the underlying reasons for the findings would be rash. A weakness in their suggestion to apply this model to broader populations is the limited patient population in which it was developed. This model has not been broadly tested in ethnically varied populations (e.g., How would this model perform in areas with larger proportions of Latinos or Pacific Islander patients?). This model also failed to find an association between non-adherence and an already validated, objective measure of non-adherence such as the medication variability index (2). The authors’ definition of non-adherence is broad and could be potentially biased by the quality of the patient–provider relationship. In addition, their model is presented as if the factors utilized to predict non-adherence are static in time (or perhaps present at the outset of the post-transplant period), even though data were collected in a retrospective review. The authors’ choice of variables to analyze in this model relied on existing data. Previous research has found an association between age at transplant, race, and gender and medication nonadherence (3). Specifically, research has found increased rates of medication non-adherence and graft loss among older adolescent African American males (4). Research has also found poorer post-transplant outcomes in adolescent African American males when compared to Latino and