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.     

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.     

Health‐related quality of life,treatment adherence,symptom experience and depression in adolescent renal transplant patients

Dobbels F, Decorte A, Roskams A, Van Damme‐Lombaerts R. Health‐related quality of life, treatment adherence, symptom experience and depression in adolescent renal transplant patients.
Pediatr Transplantation 2010:14:216–223. © 2009 John Wiley & Sons A/S. Abstract: Few studies comprehensively assessed psychological and behavioral functioning in adolescent kidney transplant patients. The purpose of this cross‐sectional study was to evaluate depression, QOL, treatment adherence and presence of side effects from the perspective of the patient and his parents, and to compare scores with norm data. All patients (age 10–18 yr) and their parents completed the following instruments: KIDSCREEN‐27 (QOL), a treatment adherence interview, the MTSOSD‐59R (side effects) and the Beck Depression Inventory (depression). Twenty‐three of 26 patients and 22 parents agreed to participate (70% male; median age 15 yr). Adolescents rated their QOL as satisfactory, but parents reported significant problems on several QOL dimensions. Depressive symptoms occurred in 17.4%, and 75% were non‐adherent with their immunosuppressive drugs (confirmed by their parents) and show other problematic health behavior, including smoking, illicit drug use, dietary non‐adherence, and suboptimal exercise levels. The most frequently occurring side effects were increased appetite, fatigue and headache; the most distressing ones were hair loss or thinning of hair, warts on hands or feet, and sores in the mouth or on the lips. Our results underscore the need for regular screening and adequate treatment of the above‐mentioned aspects.     

Perceived barriers to medication adherence in pediatric and adolescent solid organ transplantation

Comparisons of perceived barriers to adherence in pediatric and adolescent SOT have not been systematically conducted despite association between medication non‐adherence and poor outcome. Fifteen centers in CTOT‐C enrolled patients in a cross‐sectional study. Subjects' guardians completed the PMBS and subjects over eight completed the Adolescent Scale (AMBS). Association of three identified PMBS factors and subject age was assessed. Secondary analyses assessed associations between PMBS, AMBS, and patient demographics. Three hundred sixty‐eight subjects or their guardians completed PMBS or AMBS. A total of 107 subjects were 6–11 yr; 261 were ≥12. Unadjusted and propensity‐adjusted analyses indicated higher perceived barriers in guardians of adolescents as compared to guardians of pre‐adolescents medication scheduling and frustration domains regardless of organ (p < 0.05). PMBS and AMBS comparisons revealed that guardians reported fewer ingestion issues than patients (p = 0.018), and differences appeared more pronounced within younger responders for scheduling (p = 0.025) and frustration (p = 0.019). Screening revealed guardians of older patients report increased perceived barriers to adherence independent of socioeconomic status. Guardians of adolescents reported fewer perceived barriers to ingestion/side effects than patients themselves, particularly in pre‐adolescents (8–11 yr). Brief screening measures to assess perceived barriers should be further studied in adherence improvement programs.     

Medication adherence in pediatric renal transplant patients: The role of family functioning and parent health locus of control

Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio‐emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers’ perspectives, in predicting medication non‐adherence for adolescents (ages 12‐19 years) 1 year post‐transplant. Non‐adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers’ perceptions of poorer overall family functioning predicted missed medication doses (ΔR² = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem‐solving (β = ?0.795, t(21) = ?2.927, P = 0.008) and affective involvement (β = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR² = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family‐based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.     

Perceived barriers to medication adherence remain stable following solid organ transplantation

Perceived barriers to adherence have previously been investigated in SOT to identify plausible intervention targets to improve adherence and transplant outcomes. Fifteen centers in CTOTC enrolled patients longitudinally. Patients >8 years completed Adolescent Scale(AMBS) at two visits at least 6 months apart in the first 17 months post‐transplant while their guardians completed PMBS. Differences over time for pre‐identified AMBS/PMBS factors were analyzed. Perceived barrier reporting impact on subsequent TAC levels was assessed. A total of 123 patients or their guardians completed PMBS or AMBS. Twenty‐six were 6‐11 years and 97 were ≥12. The final cohort consisted of kidney (66%), lung (19%), liver (8%), and heart (7%) recipients. Unadjusted analysis showed no statistically significant change in reported barriers from visit 1 (median 2.6 months, range 1.2‐3.7 post‐transplant) to visit 2 (median 12, range 8.9‐16.5). Of 102 patients with TAC levels, 74 had a single level reported at both visits. The factor of “Disease frustration” was identified through the PMBS/AMBS questions about fatigue around medication and disease. Each point increase in “disease frustration” at visit 1 on the AMBS/PMBS doubled the odds of a lower‐than‐threshold TAC level at visit 2. No clear change in overall level of perceived barriers to medication adherence in the first year post‐transplant was seen in pediatric SOT. However, disease frustration early post‐transplant was associated with a single subtherapeutic TAC levels at 12 months. A brief screening measure may allow for early self‐identification of risk.     

Promoting medication adherence from the perspective of adolescent and young adult kidney transplant recipients,parents, and health care professionals: A TAKE‐IT TOO study

Medication non‐adherence is an important factor limiting allograft survival after kidney transplantation in AYA. Some interventions, including the TAKE‐IT, showed some success in promoting adherence but the potential for scalability and use in routine clinical practice is limited. We applied user‐centered design to gather the perspectives of recipients, parents, and health professionals concerning their needs, challenges, and potential intervention strategies to design an optimal, multi‐component medication adherence intervention. The qualitative study was conducted at four Canadian and three American kidney transplant programs. Separate focus groups for recipients, parents, and health professionals were convened to explore these stakeholders' perspectives. Directed content analysis was employed to identify themes that were shared vs distinct across stakeholders. All stakeholder groups reported challenges related to taking medications on time in the midst of their busy schedules and the demands of transitioning toward independence during adolescence. The stakeholders also made suggestions for the multi‐component behavioral intervention, including an expanded electronic pillbox and companion website, education materials, and customized digitized features to support shared responsibility and communication among recipients, parents, and health professionals. Several suggestions regarding the functionality and features of the potential intervention reported in this early stage will be explored in more depth as the iterative process unfolds. Our approach to actively involve all stakeholders in the process increases the likelihood of designing an adherence intervention that is truly user‐informed and fit for the clinical setting.     

Determinants of graft survival in pediatric and adolescent live donor kidney transplant recipients: a single center experience

To study the independent determinants of graft survival among pediatric and adolescent live donor kidney transplant recipients. Between March 1976 and March 2004, 1600 live donor kidney transplants were carried out in our center. Of them 284 were 20 yr old or younger (mean age 13.1 yr, ranging from 5 to 20 yr). Evaluation of the possible variables that may affect graft survival were carried out using univariate and multivariate analyses. Studied factors included age, gender, relation between donor and recipient, original kidney disease, ABO blood group, pretransplant blood transfusion, human leukocyte antigen (HLA) matching, pretransplant dialysis, height standard deviation score (SDS), pretransplant hypertension, cold ischemia time, number of renal arteries, ureteral anastomosis, time to diuresis, time of transplantation, occurrence of acute tubular necrosis (ATN), primary and secondary immunosuppression, total dose of steroids in the first 3 months, development of acute rejection and post-transplant hypertension. Using univariate analysis, the significant predictors for graft survival were HLA matching, type of primary urinary recontinuity, time to diuresis, ATN, acute rejection and post-transplant hypertension. The multivariate analysis restricted the significance to acute rejection and post-transplant hypertension. The independent determinants of graft survival in live-donor pediatric and adolescent renal transplant recipients are acute rejection and post-transplant hypertension.     

Parent and patient perspectives on barriers to medication adherence in adolescent transplant recipients

Abstract:  The aim of this study was to identify barriers to medication adherence in adolescent transplant recipients. Eighty adolescent transplant recipient families reported in an open-ended manner about barriers to medication adherence. These responses were then coded to reflect potentially important themes associated with medication adherence. The themes derived included: forgot/distracted, poor planning/scheduling issues, physical barriers/medication issues, and voluntary resistance/attempts to be normal. Inter-rater reliability for barrier coding was very high ( k  = 0.91). Patients who were classified as non-adherent reported significantly more overall barriers, more forgot/distracted barriers, and more voluntary resistance/attempts to be normal barriers than those classified as adherent. Non-adherence was also found to be more likely when adolescents, as opposed to parents, were responsible for administering the medication. Further, non-adherence was more likely when taking morning rather than evening doses. These findings are explained with an emphasis on potential remedies that directly address the stated barriers.     

Developmental and disease-related influences on self-management acquisition among pediatric liver transplant recipients

Pediatric LT recipients are vulnerable to disruptions in their healthcare management and transitioning to self-managed care. This study aimed to examine whether age at transplant and indication for transplant (acute vs. chronic liver disease) influence later self-management skills. Sixty-three LT recipients, aged 14 and older (M = 17.68, s.d. = 3.01), were recruited and asked to complete a healthcare management survey, the Developmentally Based Skills Checklist, adapted for transplant patients, listing 22 behaviors that medically ill adolescents should progressively master. While there were no significant differences between those who received an LT owing to an acute disease vs. those who received an LT owing to a chronic disease, the age at which patients received their transplant did yield significant results, although, overall, these findings were attenuated by current age. However, our findings indicated that males transplanted at a younger age struggled with mastery over their healthcare responsibilities relative to males transplanted later and females in both age groups. There are many possible reasons why the experience of transplant at a younger age could negatively affect or derail healthcare transitions. Future research is necessary to further untangle this relationship; yet, it seems as though longer time living with LT may make transition harder for families.     

A typology of non-adherence in pediatric renal transplant recipients

We reviewed 112 pediatric renal transplant recipients to document the rate of medication non-adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent-child conflict were the major factors related to NA.     

Adherence and health-related quality of life in adolescent liver transplant recipients

Abstract:  Adolescence is a particularly high-risk period for non-adherence with post-transplant medical regimens. There remains a lack of research investigating factors related to non-adherence in adolescent LT recipients. The present study empirically assessed the relationship between adherence and HRQOL in adolescent LT recipients. Participants included 25 adolescents (mean = 15.1 yr, range 12–17.9) and their parent/guardian(s). Adherence was assessed using multiple indices including clinician-conducted interviews, rate of clinic attendance, and s.d. of consecutive tacrolimus blood levels. HRQOL was examined using self-report and parent-proxy report on well-validated assessment measures. Results indicated that 76% of participants were non-adherent on at least one measure of adherence, and HRQOL was significantly lower than normative data for healthy children. Tacrolimus s.d. were significant related to poor HRQOL across domains of physical, school, and social functioning. Non-adherent adolescents reported poorer health perceptions, self-esteem, mental health, family cohesion, and more limitations in social and school activities related to physical, emotional, and behavioral problems. These results suggest that empirically based assessment of HRQOL may help identify those at highest risk for behavior, emotional and school difficulties, as well as non-adherence. The examination of tacrolimus s.d. may also help identify patients who may benefit from intervention to promote adherence and HRQOL. Prospective investigations are necessary to further identify the impact of HRQOL on adherence and long-term health outcomes to further guide clinical intervention.     

The impact of sirolimus on sex hormones in male adolescent kidney recipients

While it is known that sirolimus affects sex hormones in adult kidney transplant patients, there is a scarcity of data on its effects on sex hormone levels in adolescent kidney recipients. The objective of this study is to describe the impact of sirolimus on the sex hormones in this patient population. This is a retrospective review of male adolescent renal transplant patients transitioned to sirolimus. Baseline and subsequent annual testosterone levels were collected. Linear regression was undertaken to determine the predictors of testosterone levels. Four African Americans and 11 Caucasians, median age of 15 yr (11-18) in 2008, were included. Mean time post-transplant was 81 ± 37 months. Mean testosterone values were the following: 336 ± 135 ng/dL (n = 8) at baseline, 349 ± 130 ng/dL (n = 15) one yr later, and 360 ± 132 ng/dL (n = 13) two yr later (normal range for adult males: 350-970 ng/dL). Seven (47%) patients experienced a decrease in testosterone levels. Time on sirolimus was associated with decreased testosterone (r = 0.643, p = 0.010). Testosterone levels in pubertal male kidney transplant recipients on sirolimus may be suppressed, especially if they have been treated with sirolimus for several years. These data need to be confirmed in a larger study.     

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.     

Tailoring immunosuppressive therapy for renal transplant recipients

During the past decade several new potent immunosuppressive agents with different modes of action and different side-effect profiles have become available. Nowadays immunosuppression after renal transplantation is no longer one single regimen applicable to all patients. In the selection of the optimal immunosuppressive protocol, individual drug-related toxicity, recipient-related risk factors as well as donor organ characteristics have to be taken into account. This article will give an overview of the most recently developed immunosuppressive agents available for clinical use. Their individual mode of action and their different efficacy and safety profile will be described as basis for selection of each of these drugs in an attempt to tailor the optimal therapeutic regimen for the individual patient both in terms of short-term and long-term outcome.     

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.     

Impact of a pharmacist‐led vaccine recommendation program for pediatric kidney transplant candidates

Pediatric transplant recipients commonly have deficient vaccination status at the time of transplantation. Utilizing transplant pharmacists to improve vaccination rates has not previously been described. This single‐center, retrospective study evaluated the impact of transplant pharmacist interventions on the completion rate of vaccination schedules at time of kidney transplant. Patients who received pharmacist‐led vaccination recommendations prior to transplant were compared to patients without pharmacist recommendations. Forty‐seven pediatric patients were included: 24 intervention patients and 23 control patients. The median percentage of up‐to‐date vaccinations at time of transplant was significantly higher in intervention group (91%; IQR 86%‐100%) vs. control group (80%; IQR 71%‐80%) (P<.0001). The median change in up‐to‐date vaccinations from time of evaluation to time of transplant was also significantly higher in the intervention group (7.5%) compared to the control group (0%) (P<.0001). There was no difference in live vaccination rates. No patients in either group were readmitted for a vaccine‐preventable disease within 6 months post‐transplant. With pharmacist intervention, significantly more patients were up to date with vaccination schedules at the time of transplant. These results suggest that a transplant pharmacist may serve as a valuable resource to increase vaccination schedule compliance between time of evaluation and transplantation.