Empowering patients to adhere to their treatment regimens: A multifaceted approach

It is well‐recognized that adolescence and early adulthood are a high‐risk period for non‐adherence with treatment regimens in solid organ transplant recipients, leading to high rates of rejection and graft loss (Transplantation, 92, 2011, 1237; Pediatr Transplant, 9, 2005, 381; Transplantation, 77, 2004, 769). Preventing medication non‐adherence is the holy grail of transplant adolescent care. If we can determine how best to support our patients in taking their daily medications as prescribed, we can improve long‐term health, reduce need for re‐transplantation, and reduce healthcare costs. In the last few years, several studies have provided us with additional insights into potentially effective interventions and have highlighted existing gaps in knowledge. This article reviews recent literature published over the last 5 years on the topic of adherence in transplant recipients, highlighting insights and opportunities to promote adherence at the individual patient level, family level, healthcare system level, and community level. Above all, the recent work that is highlighted suggests that adherence interventions for prevention and treatment must be multifaceted, individualized, and longitudinal to be effective.     

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.     

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.     

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.     

Group cell phones are feasible and acceptable for promoting optimal breastfeeding practices in a women's microcredit program in Nigeria

As part of a breastfeeding promotion intervention trial in Nigeria, we provided one cell phone per group of 5–7 microcredit clients and instructed the group's cell phone recipient to share weekly breastfeeding voice and text messages with group members. We measured the feasibility and acceptability of using group cell phones by conducting semi‐structured exit interviews with 195 microcredit clients whose babies were born during the intervention (target group), in‐depth interviews with eight phone recipients and nine non‐phone recipients, and 16 focus group discussions with other microcredit clients. Women in the target group said the group phone worked well or very well (64%). They were motivated to try the recommended practices because they trusted the information (58%) and had support from others (35%). Approximately 44% of target women reported that their groups met and shared messages at least once a week. Women in groups that met at least weekly had higher odds of exclusive breastfeeding up to 6 months (OR 5.6, 95% CI 1.6, 19.7) than women in groups that never met. In‐depth interviews and focus group discussions indicated that non‐phone recipients had positive feelings towards phone recipients, the group phone met participants' needs, and messages were often shared outside the group. In conclusion, group cell phone messaging to promote breastfeeding among microcredit clients is feasible and acceptable and can be part of an effective behaviour change package.     

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.     

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.     

Adherence to recommendations on lipid‐based nutrient supplement and iron and folic acid tablet consumption among pregnant and lactating women participating in a community health programme in northwest Bangladesh

Limited knowledge exists on sustained adherence to small‐quantity lipid‐based nutrient supplements for pregnant and lactating women (LNS‐PL) and how this compares with that of other prenatal supplements. To address these gaps, a random subsample of women (n = 360) during pregnancy, early (6‐ to 12‐week post‐partum) and late (12‐ to 24‐week post‐partum) lactation, from an ongoing effectiveness trial in Bangladesh, was selected for in‐home interviews about LNS‐PL or iron/folic acid (IFA) use and preferences. Prevalence of high adherence (≥70% of the recommendation) based on self‐reported supplement consumption was 67%, 68% and 81% among LNS‐PL recipients during pregnancy, early and late lactation, and was 87% and 71% among IFA recipients during pregnancy and early lactation, respectively (P = 0.044). Programmatic factors (e.g. distribution and visits by programme staff) were consistently statistically significantly associated with reported high adherence. Among LNS‐PL recipients, high overall supplement acceptability score [odds ratio (OR): 8.62; 95% confidence interval (CI) 3.53, 20.83] and use of reminder techniques (OR: 4.41; 95%CI 1.65, 11.76) were positively associated, and reported vomiting at enrollment was negatively associated (OR: 0.34; 95%CI 0.14, 0.80), with reported high adherence. Selected women (n = 16) and key informants (n = 18) participated in in‐depth interviews about perceptions and acceptability of LNS‐PL. Women perceived benefits of taking LNS‐PL, but some faced barriers to consumption including aversion to odour and taste during pregnancy, forgetfulness and disruptions in supply. To achieve high adherence, results from this study suggest that maternal supplementation programmes should focus on programmatic barriers and consider incorporating reminder techniques. Organoleptic acceptability of LNS‐PL, particularly during pregnancy, may also need to be addressed.     

Assessing allocation of responsibility for health management in pediatric liver transplant recipients

Given the increased risk for non‐adherence and poor health outcomes in late adolescence, there is a need for better methods to evaluate and improve the transition process as adolescent patients are prepared to be independent adults. This study assessed the psychometrics and concurrent validity of a newly developed measure of AoR for health management in pediatric liver transplant patients. A total of 48 patients and 37 parents completed a 13‐item measure of AoR. We performed an exploratory PCA on survey results and used component scores to assess the relationship between AoR and age, age at transplant, adherence, and health outcomes. Two primary components were identified: communication with the healthcare system and self‐management tasks. Parent perception of adolescent responsibility for tasks related to communicating with the healthcare system was correlated, in younger patients, with increased non‐adherence while responsibility for tasks related to self‐management was correlated, in older patients, with decreased non‐adherence. These results support AoR as a two‐domain construct, and they provide targets for monitoring and intervention as adolescent patients advance toward transfer.     

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.     

Usability testing of the Internet program: “Teens Taking Charge: Managing My Transplant Online”

Adolescents with SOT demonstrate high rates of medication non‐adherence and higher rates of graft loss compared to all other age groups. Self‐management interventions encompass information‐based material designed to achieve disease‐related learning and changes in the participant's knowledge and skill acquisition, while providing social support. These interventions have had some success in chronic disease populations by reducing symptoms and promoting self‐efficacy and empowerment. Using findings from a needs assessment, an Internet‐based self‐management program, Teens Taking Charge: Managing My Transplant Online, for youth with SOT was developed. This program contains information on transplant, self‐management and transition skills, and opportunities for peer support. The purpose of this study was to determine the usability and acceptability of the initial three modules (Medication and Vaccines; Diet after Transplant; and Living with a Transplant Organ) of the online program from the perspectives of youth with SOT. Participants were recruited from SOT clinics at a large pediatric tertiary care center in Canada. Three iterative cycles (seven patients per iteration) of usability testing took place to refine the Web site prototype. Study procedures involved participants finding items from a standardized list of features and talking aloud about issues they encountered, followed by a semi‐structured interview to generate feedback about what they liked and disliked about the program. All 21 patients (mean age = 14.9 yr) found the Web site content to be trustworthy, they liked the picture content, and they found the videos of peer experiences to be particularly helpful. Participants had some difficulties finding information within submodules and suggested a more simplistic design with easier navigation. This web‐based intervention is appealing to teenagers and may foster improved self‐management with their SOT. Nine additional teen and two parent modules are being developed, and the completed Web site will undergo usability testing. In the future, a randomized control trial will determine the feasibility and effectiveness of this online self‐management program on adherence, self‐efficacy, and transition skills.     

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.     

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.     

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.     

Psychosocial predictors of medication adherence in pediatric heart and lung organ transplantation

Few studies have identified the psychosocial characteristics of those children and their families associated with future non‐adherence to immunosuppressive medications following a heart or lung transplant. UNOS data and medical records information were used to test the association between patient and family psychosocial characteristics and medication adherence. Medication adherence outcomes were obtained using the physician assessments in the UNOS data and measured through patient‐level standard deviation scores of immunosuppressive medication blood levels. Complete data were collected on 105 pediatric heart and lung transplant recipients and their families. Multivariate, stepwise analyses were conducted with each adherence outcome. Physician reports of adherence were associated with age of the child at transplantation, parental education, two‐parent families, significant psychosocial problems, and the pretransplant life support status of the child. The resulting model (χ²=28.146, df=5, P<.001) explained approximately 39.5% of the variance in physician reports of adherence (Nagelkerke r²=.395). Blood level standard deviation scores were predicted by age at transplant (F=5.624, P=.02, r²=.05). Results point to the difficulties experienced by children and families when undergoing a heart or lung transplantation. Efforts to develop standardized and evidence‐based pretransplant psychosocial assessments in pediatric populations are suggested, especially those surrounding familial risk factors.     

Predictors of medication adherence in children receiving psychotropic medication

Aim: Medication adherence is poor in many young people with chronic illness. However, little research has examined medication adherence in clinic samples of young people receiving psychotropic medication, and whether factors such as disorder or drug type influence adherence. This study aimed to examine medication adherence in children and adolescents receiving psychotropic medication. Methods: Young people receiving psychotropic medication and their caregivers were recruited from pharmacy and mental health services within a large metropolitan hospital. A brief cross‐sectional survey examined medication history, missed doses within the previous week and other clinical information. Multiple regression analysis examined whether child characteristics, drug type and regimen characteristics were associated with medication adherence. Results: Poor adherence was associated with lack of parental involvement in medication routines (P < 0.05), use of complementary medicines (P < 0.01) and difficulty remembering doses (P < 0.01). Developmental diagnoses (P < 0.05), use of antipsychotics (P < 0.05) and use of concomitant non‐psychotropic medication (P < 0.05) were predictors of good adherence. Conclusion: Encouraging parental involvement in medication routines may be a practical target for clinicians aiming to improve medication adherence in young people. Use of complementary medicines may indicate a group with a higher risk of poorer adherence.     

Growing pains: non-adherence with the immunosuppressive regimen in adolescent transplant recipients

One-year graft and patient survival are better in adolescent transplant recipients (age 11-19 years) than in younger (age < 11 years) pediatric transplant recipients. However, several groups found that long-term outcomes (> i.e. 5 year post-transplant) in the adolescent age group are significantly worse than in younger transplant recipients. A behavioral factor that could explain an important part of the poorer clinical outcome in adolescent transplant recipients is non-compliance with medication taking. Adolescents, like all organ transplant recipients irrespective of their age, must adhere to a life-long immunosuppressive regimen in addition to other aspects of their therapeutic regimen. Therefore, adolescent transplant recipients, as all transplant patients, should be regarded as a chronically ill patient population in whom behavioral and psychosocial management is equally important as state-of-the-art medical management. This paper provides an overview of the current knowledge on prevalence, clinical consequences, and risk-factors for non-compliance with the immunosuppressive regimen in adolescent transplant recipients and offers some suggestions for adolescent-tailored interventions to improve medication adherence.     

Perceived barriers to adherence among adolescent renal transplant candidates

Non-adherence to medical regimens is a ubiquitous hindrance to quality health care among adolescent transplant recipients. Identification of potentially modifiable barriers to adherence when patients are listed for organ transplant would help with early intervention efforts to prepare adolescents for the stringent medication regimen post-transplant. Fifty-six adolescents listed for a kidney transplant, mean age 14.27 (s.d. = 2.2; range 11-18 yr), 73.2% male, 62.5% Caucasian participated in a semi-structured interview, the Medical Adherence Measure, to assesses the patient's knowledge of the prescribed regimen, reported adherence (missed and late doses), the system used to organized medications, and who holds the primary responsibility over medication management. Better knowledge of the medication regimen was associated with fewer missed doses (r = -0.48, p < 0.001). Patients who perceived more barriers had more missed (r = 0.38, p = 0.004) and late (r = 0.47, p < 0.001) doses. Patients who endorsed "just forget," the most common barrier (56.4%), reported significantly more missed (z = -4.25, p < 0.001) and late (z = -2.2, p = 0.02) doses. Only one-third of the transplant candidates used a pillbox to organize medications but these patients had significantly better adherence, z = -2.2, p = 0.03. With regard to responsibility over managing the regimens, adolescents missed fewer doses when their parents were in charge than when they were solely responsible, z = -2.1, p = 0.04. Interventions developed to prepare transplant candidates for a stringent post-transplant regimen need to focus on ensuring accurate knowledge of as simple a regimen as possible. Use of an organized system such as a pillbox to establish a routine and facilitate tracking of medications is recommended with integration of reminders that may be appealing for this age group. Although individuation is developmentally normative at this age, parent involvement seems critical until the adolescent is able to manage the responsibility more independently.     

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.