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Adolescent non-adherence: Prevalence and consequences in liver transplant recipients
Abstract
Few studies have examined the prevalence, demographic variables and adverse consequences associated with non-adherence to immunosuppressive therapy in the adolescent liver transplant population. Our hypothesis is that a significant proportion of adolescent liver transplant recipients exhibit non-adherence to medical regimens and that certain demographic and medical condition-related characteristics can be identified as potential predictors of non-adherent behavior. Furthermore, non-adherence leads to a greater incidence of morbidity and mortality in this population as compared with the adherent subset of adolescent patients. We reviewed the charts of 97 patients from 1987 to 2002 who by December of 2002 had survived at least 1 yr post-transplant and were followed by the Pediatric Liver Transplant Service at any point during their adolescent period (ages of 12-21). Non-adherence was defined as documentation of a report of non-adherence by a patient, parent or healthcare provider that was recorded in the patient's legal medical record. Descriptive statistics were used to determine the prevalence, demographic variables and adverse outcomes associated with non-adherence to immunosuppressive therapy. Categorical variables were analyzed using the chi-square test or the Fisher exact probability test. The unpaired Student's t-test was used to analyze the continuous variable of age at transplant. Using the inclusion criteria, a total of 97 patients represented the study sample of whom 37 subjects (38.1%) were defined as non-adherent and 60 (61.8%) were adherent. Non-adherent subjects were more likely to be female, older (>18 yr) and from a single-parent household. There was no significant difference in immunosuppressive regimen between non-adherent and adherent patients. Non-adherence was significantly (p<0.025) associated with lower socioeconomic status (SES), older age at transplant (p<0.005, 95% CI: -5.5 to -.99, Student's t-test) and episodes of late acute rejection (p<.001). Non-adherence was also significantly associated with re-transplantation and death secondary to chronic rejection by the Fisher exact test (p<0.006 and p<0.05, respectively). Non-adherence to immunosuppressive therapy is a prevalent problem that is correlated with certain demographic and medical condition-related risk factors and more frequent adverse consequences in the adolescent liver transplant population. The greater incidence of late acute rejection, death and re-transplantation owing to chronic rejection in non-adherent patients suggests that non-adherence is significantly associated with an increased risk of morbidity and mortality. Further investigation to identify patients at greatest risk for non-adherence is necessary to design the most effective intervention to increase patient survival and well being.
... Several demographic factors have been found predictive of medication non-adherence in prior studies (Dew et al., 2009;Killian et al., 2018). Patient age remains among the most studied factors with older patients, especially those in adolescence, having greater non-adherence (Berquist et al., 2006;Bilhartz et al., 2015;Connelly et al., 2015;Killian, 2017;Shaw et al., 2003). Research has produced differing findings as to patient gender as a risk factor for post-transplant non-adherence and other posttransplant health outcomes. ...
... Greater non-adherence has been reported among African-American or ethnic minority patients and families (Connelly et al., 2015;Jarzembowski et al., 2004;Oliva et al., 2013;Simons et al., 2009aSimons et al., , 2009bTucker et al., 2001). Lower socio-economic status as indicated by receipt of public medical insurance has predicted post-transplant non-adherence in samples of liver transplant recipients (Berquist et al., 2006(Berquist et al., , 2008de Oliveira et al., 2017), heart and lung transplant recipients (Davies et al., 2013;Killian, 2017;Oliva et al., 2013), and multiple organ types (Simons et al., 2009a(Simons et al., , 2009b. ...
... Gender also influenced adherence with female patients demonstrating greater adherence than males, but gender did not directly influence LAR. Male patients have been found to be at greater risk for poor adherence in prior research (Connelly et al., 2015;Seyedan, 2011;Tucker et al., 2002), yet greater non-adherence has also been found among older female children (Berquist et al., 2006). Analyses examining the interaction between patient age and gender, when predicting adherence where differences in adherence rates between male and female patients vary significantly depending on their age (Killian et al., 2018), were inconclusive across the two sets of models (i.e., with and without controlling for years of MLVI). ...
Few studies in pediatric solid organ transplantation have examined non-adherence to immunosuppressive medication over time and its associations with demographic factors and post-transplant outcomes including late acute rejection and hospitalizations. We examined longitudinal variation in patient Medication Level Variability Index (MLVI) adherence data from pediatric kidney, liver, and heart transplant recipients. Patient and administrative data from the United Network for Organ Sharing were linked with electronic health records and MLVI values for 332 patients. Multilevel mediation modeling indicated comparatively more variation in MLVI values between patients than within patients, longitudinally, over 10 years post transplant. MLVI values significantly predicted late acute rejection and hospitalization. MLVI partially mediated patient factors and post-transplant outcomes for patient age indicating adolescents may benefit most from intervention efforts. Results demonstrate the importance of longitudinal assessment of adherence and differences among patients. Efforts to promote medication adherence should be adapted to high-risk patients to increase likelihood of adherence.
... If not properly managed, this response may lead to cellular rejection with possible graft loss. 1 Therefore, most transplant recipients require specific long-term immunosuppression. [1][2][3][4][5] Starting in 1990, tacrolimus has been widely used as a primary immunosuppressant in solid organ and tissue transplantation. 1 Tacrolimus is classified as a calcineurin inhibitor and interferes with T-cell activation. 6 Additionally, tacrolimus has wide interindividual and intra-individual pharmacokinetic variability and a narrow therapeutic index. ...
... However, in the field of pediatric transplantation, studies have focused primarily on the adolescent age group. [2][3][4]7,[11][12][13] Studies have previously identified correlation between non-adherence and certain demographic variables such as female gender, low socioeconomic status, younger age, and single parent home suggesting a risk profile that may be used to identify patients at greatest risk of adverse consequences for the graft. 3,7,10 This was demonstrated both in adolescents and children under 10 years old. ...
... [2][3][4]7,[11][12][13] Studies have previously identified correlation between non-adherence and certain demographic variables such as female gender, low socioeconomic status, younger age, and single parent home suggesting a risk profile that may be used to identify patients at greatest risk of adverse consequences for the graft. 3,7,10 This was demonstrated both in adolescents and children under 10 years old. 10 The application of MLVI as an objective marker of adherence in child-age pediatric transplant recipients has been understudied. ...
MLVI has been used to assess adherence. To determine the MLVI in children <12 years of age at transplantation and to identify demographic correlates and consequences for the graft. This is a retrospective study of 50 outpatients (4.0 ± 3.5 years), at least 13-month post-liver transplantation. The outcomes evaluated were MLVI, ALT > 60 IU/L, ACR, death, and graft loss. We analyzed demographic and socioeconomic characteristics, indication for transplantation, and type of donor. Student's t test and the chi-square test were used. Statistical significance was set at P ≤ .05. Seventy-two percent were infants or preschoolers, 62% biliary atresia. Seventy-four percent of the mothers had middle-school education, and 54% of the families had an income ≤3632.4 US$/y. Twenty-two (44%) patients had a MLVI ≥ 2 SD; this was more prevalent in families with higher incomes (P = .045). ALT levels > 60 IU/L were more common in MLVI ≥ 2 SD group (P = .035). ACR episodes were similar between groups (P = 1.000). No patient died or lost the graft. MLVI ≥ 2 SD may be an indicator of the risk of medication non-adherence.
... More than other factors, adherence to immunosuppressive medications is critical to a transplant recipient's survival and quality of life (1)(2)(3)(4). Rates of immunosuppressant medication non-adherence range from 4% to 60% in samples of children and adolescents after organ transplantation with several meta-analyses estimating an average of approximately 30% (4)(5)(6)(7). ...
... The role of gender as a predictor of posttransplant adherence is less clear. Male pediatric transplant recipients may exhibit greater non-adherence (11), though other studies have reported adolescent females as more non-adherent after renal transplantation (12,13) and liver transplantation (2). A review of adherence research found no significant association between gender and medication adherence (8). ...
... Gender was not found to be a significant predictor of adherence even when statistically controlling for age of the recipient. Though prior studies have found significant effects of gender such as greater non-adherence among groups of adolescent female recipients (2) or male renal transplant recipients (13), a meta-analytic review of the literature did not find gender associated with non-adherence (8). ...
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 (χ(2) =28.146, df=5, P<.001) explained approximately 39.5% of the variance in physician reports of adherence (Nagelkerke r(2) =.395). Blood level standard deviation scores were predicted by age at transplant (F=5.624, P=.02, r(2) =.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.
... 11 Non-adherence remains a significant predictor of poor posttransplant outcomes. 1,5 Adolescent patients have greater number of rejection episodes [15][16][17] and earlier incidence of the first rejection episode when compared to younger children. 18 Few appropriate interventions are available to target medication adherence in pediatric organ transplant recipients, let alone higher risk adolescents. ...
... 20,21 The need to develop and examine mHealth approaches for patient care, especially those addressing critical health behaviors, has increased dramatically due to the COVID-19 pandemic. 22,23 Increased access and use of personal technology and mobile smart devices among adolescents and their families [24][25][26][27][28] with an estimated rate of 81.1% for adolescents (ages [12][13][14][15][16][17] and 95.7% for young adults (ages [18][19][20][21][22][23][24] 29 has allowed the exponential increase in mHealth approaches. Moreover, broadband adoption and access have increased nationally, even among younger populations and those of lower socio-economic means. ...
Purpose:
HT recipients experience high levels of medication non-adherence during adolescence. This pilot study examined the acceptability and feasibility of an asynchronous DOT mHealth application among adolescent HT recipients. The app facilitates tracking of patients' dose-by-dose adherence and enables transplant team members to engage patients. The DOT application allows patients to self-record videos while taking their medication and submit for review. Transplant staff review the videos and communicate with patients to engage and encourage medication adherence.
Methods:
Ten adolescent HT recipients with poor adherence were enrolled into a single-group, 12-week pilot study examining the impact of DOT on adherence. Secondary outcomes included self-report measures from patients and parents concerning HRQOL and adherence barriers. Long-term health outcomes assessed included AR and hospitalization 6 months following DOT.
Findings:
Among 14 adolescent HT patients approached, 10 initiated the DOT intervention. Of these, 8 completed the 12-week intervention. Patients and caregivers reported high perceptions of acceptability and accessibility. Patients submitted 90.1% of possible videos demonstrating medication doses taken. MLVI values for the 10 patients initiating DOT decreased from 6 months prior to the intervention (2.86 ± 1.83) to 6 months following their involvement (2.08 ± 0.87) representing a 21.7% decrease in non-adherence, though not statistically significant given the small sample size.
Conclusions:
Result of this pilot study provides promising insights regarding the feasibility, acceptability, and potential impact of DOT for adolescent HT recipients. Further randomized studies are required to confirm these observations.
... Previous studies have reported variable rates of non-adherence to treatment protocols in teenagers with liver transplants, from as low as 17% to as high as 76% [6][7][8]. Non-adherence with immunosuppression regimens and poor follow-up is strongly correlated with worse clinical outcomes in teenage transplant patients, including transplant rejection, graft loss, and death [8][9][10][11][12][13][14][15]. It is a major contributing factor to the high rates of graft loss in teenage and early adult years compared to other age groups [1,2,7,9,10,13,16]. ...
... Non-adherence with immunosuppression regimens and poor follow-up is strongly correlated with worse clinical outcomes in teenage transplant patients, including transplant rejection, graft loss, and death [8][9][10][11][12][13][14][15]. It is a major contributing factor to the high rates of graft loss in teenage and early adult years compared to other age groups [1,2,7,9,10,13,16]. As we published last year, 3-year patient survival and graft survival was significantly lower in those who underwent liver transplant at age 16-17 years old compared to younger children [4]. ...
Purpose of review:
Many pediatric liver transplant patients are surviving to adulthood, and providers have come to recognize the importance of effectively transitioning these patients to an adult hepatologist. The review aims to analyze the most recent literature regarding patient outcomes after transition, barriers to successful transition, recommendations from clinicians and medical societies regarding transition programs, and to provide personal insights from our experience in transitioning liver transplant recipients.
Recent findings:
While results were variable between studies, many recent reports show significant morbidity and mortality in patients following transition to adult care. Medical non-adherence is frequently seen in adolescents and young adults both prior to and after transition, and is consistently associated with higher rates of rejection, graft loss, and death. In general, transplant programs with a formal transition process had better patient outcomes though recent findings are mostly-single center and direct comparison between programs is difficult. Societal recommendations for how to create a transition program contain a number of common themes that we have categorized for easier understanding. Successful transition is vital to the continued health of pediatric liver transplant patients. While an effective transition program includes a number of key components, it should be individualized to best function within a given transplant center. Here, we have reviewed a number of recent single-center retrospective studies on transition, but multi-site retrospective or prospective data is lacking, and is a fertile area for future research.
... Patient social factors predicting outcomes across the time frames in the current study included patient age, ethnicity, level of education, and gender, which have been reported as important predictors in prior research [14,27,[31][32][33]. Female and adolescent patients have been shown to be at greater risk for rejection episodes [34][35][36] and mortality compared to male or younger patients [37][38][39][40][41]. ...
Background
Prediction of post-transplant health outcomes for pediatric heart transplantation is critical for high quality post-transplant care. The purpose of the current study is to examine the use of machine learning models to predict late acute rejection, hospitalizations, and mortality for pediatric heart transplant recipients.
Methods
Various traditional machine learning and deep learning models were used to predict late acute rejection, hospitalizations, and mortality at 1-, 3-, and 5-years post-transplant in pediatric heart transplant recipients using the national United Network for Organ Sharing data. Variables predicting post-transplant outcomes included donor and recipient medical and social predictors. SHAP (SHapley Additive exPlanations) were calculated to estimate the importance of each variable for prediction and to increase the interpretability of modeling results.
Results
Logistic regression, random forest, and adaptive boosting models were the best performing algorithms for different prediction windows across outcomes. Based on the area under the receiver operating curve, models predicting rejection and mortality were found to be more accurate than those predicting hospitalizations.
Conclusions
Machine learning approaches can identify unique risk factors, their complex relationship with outcomes using prediction modeling, thereby aiding in identifying at-risk patients, providing a solid foundation for improved clinical care, risk stratification, and guiding decision-making within pediatric organ transplant centers. The current study demonstrates the value of machine learning approaches for modeling post-transplant health outcomes using patient-level data and informs the transplant community about the future potential of these innovative approaches to improve pediatric post-heart transplant care.
... Age and gender were both identified in numerous post-transplant models as predictive of hospitalizations. Older age at transplant and current patient age have been found to predict lower post-transplant health-related quality of life [61], more rejection episodes (both acuteand chronic)[ [62][63][64], and greater mortality riskwhen compared toyounger children across organ type [55,65]. Female patients have reported poor posttransplant outcomes in studies of pediatric kidney [55,66,67] and heart [68] recipients. ...
Objectives
Prediction of post-transplant health outcomes and identification of key factors remain important issues for pediatric transplant teams and researchers. Outcomes research has generally relied on general linear modeling or similar techniques offering limited predictive validity. Thus far, data-driven modeling and machine learning (ML) approaches have had limited application and success in pediatric transplant outcomes research. The purpose of the current study was to examine ML models predicting post-transplant hospitalization in a sample of pediatric kidney, liver, and heart transplant recipients from a large solid organ transplant program.
Materials and Methods
Various logistic regression, naive Bayes, support vector machine, and deep learning (DL) methods were used to predict 1-, 3-, and 5-year post-transplant hospitalization using patient and administrative data from a large pediatric organ transplant center.
Results
DL models generally outperformed traditional ML models across organtypes and prediction windows with area under the receiver operating characteristic curve values ranging from 0.750 to 0.851. Shapley additive explanations (SHAP) were used to increase the interpretability of DL model results. Various medical, patient, and social variables were identified as salient predictors across organ types.
Discussion
Results demonstrate the utility of DL modeling for health outcome prediction with pediatric patients, and its use represents an important development in the prediction of post-transplant outcomes in pediatric transplantation compared to prior research.
Conclusion
Results point to DL models as potentially useful tools in decision-support systems assisting physicians and transplant teams in identifying patients at a greater risk for poor post-transplant outcomes.
... 5 Medication non-adherence is especially prevalent in adolescent transplant populations with an estimated non-adherence rate of 15%-40%. [6][7][8][9][10] Factors associated with non-adherence in this population are extensive and include low socioeconomic status, family instability, limited parental supervision, depression, poor coping, disease frustration, longer time since transplant, side effects associated with immunosuppressive medication, and poor knowledge about the risks of medication non-adherence. 5,11,12 Researchers have studied numerous direct and indirect methods to assess medication adherence in pediatric patients. ...
Given the complexity of the pediatric post‐transplant medication regimen and known medication adherence difficulties within the solid organ transplant population, interventions to improve adherence continue to be explored and fine‐tuned. Advances in technology have led to the development of new programs aimed at improving medication adherence and the overall care of transplant patients. This manuscript describes implementation of a DMP where transplant patients' medications were co‐encapsulated with ingestible sensors, and adherence was monitored via a patient mobile application and a provider portal. The benefits and challenges of the DMP as reported by patients, caregivers, and medical providers are explored in this manuscript. Participant feedback regarding best practices highlighted these benefits: ease of use/intuitive technology, sense of improved communication with medical team, increased knowledge and motivation around treatment regimen, and positive self‐reports of medication adherence. Challenges included reluctance to participate (n = 43, 54.43% of patients approached declined participation) and patch wearability difficulties reported by participants (n = 20; 68.97%). Other notable challenges included the following: limited drug profile compatibility with the DMP technology and concerns about privacy and electronic data sharing for patients who chose not to participate. DMP implementation highlighted how technological advances offer novel methods to assess adherence, enhance medical decision‐making, and can potentially improve clinical outcomes. Although numerous benefits of the program were recognized by participants, challenges were identified and the DMP technology and medication panel continues to be refined; further investigation of such programs continues to be warranted.
... In the current study, HCPs reported concerns about non-adherence in adolescent and young adult patients. As there is increased morbidity and mortality in non-adherent liver transplant patients compared to young people who are adherent, 24 this was a particular concern. The feeling of being different was attributed to be one of the likely causes of non-adherent behaviour by all the HCPs in the study which is in line with other studies exploring young people's experiences of life with a liver transplant. ...
Introduction:
Transition from pediatric to adult services of young people with a liver transplant is an important priority due to increasing numbers of young people surviving into adulthood. There is increased incidence of graft loss and non-adherence following transfer to adult services. Although studies have considered the views and perceptions of young people who have undergone liver transplantation and their parents about transition, there is currently no qualitative research with healthcare professionals working in the field of liver transplantation. The aim of this study was to elicit the views of this group of stakeholders about barriers and facilitators of an effective transition process.
Methods:
Semi-structured interviews were carried out with 11 HCPs from pediatric and adult liver transplant programs and from a range of professional backgrounds. Interviews were transcribed verbatim and analyzed using thematic analysis.
Results:
Four themes were identified: "non-adherence and psychosocial issues," "need for better psychological support," "the role of parents," and "the emotional impact of transition on healthcare professionals." Within these themes, professionals described factors which hindered or promoted an effective transition process.
Conclusions:
Screening tools which address psychological and social aspects of the lives of young people should be used in routine practice to identify patients requiring psychosocial support and to identify those at risk of non-adherence. All staff involved with transition should be trained in the use of psychosocial screening strategies. The development of a formal referral pathway so that young people can access psychological support in adult services is recommended.
... Twenty studies assessed medication adherence by nonobjective methods: questionnaires or interviews (n=16), the opinion of physicians and/or nurses (n=4), retrospective chart review (RCR; n=3). RCR evaluated the number of patient records documenting medication non-adherence: the medication adherence reported in the 3 studies was 50%, 28 62%, 27 and 91%. 34 Among the 4 studies using the opinion of physicians and/or nurses, 13,19,23,26 2 reported medication adherence by this method: 52% 19 and 61%. ...
Background: Medication adherence is a major concern in public health. It is fully established that immunosuppressive therapy (IT) and concomitant medications affect transplant outcomes in the pediatric population, showing interest in adherence to this therapy. The aim of the present review was to report on medication adherence in pediatric population post-transplantation. This will enable us to know the situation in this particular population.
Methods: A literature search was performed using the MEDLINE database. Studies that were published from January 1999 to January 2016 in English language and which investigated medication adherence in pediatric transplantation were included. The type of organ and the methods used to assess medication adherence were studied.
Results: A total of 281 records were identified, from which 34 studies were selected: 38% (n=13) on kidney transplantation, 32% (n=11) on liver transplantation, and 23% (n=10) on the transplantation of other organs. Medication adherence was found to be lower than 80% in two-thirds of the studies (64%), and varied from 22% to 97%. This wide range was explained in part by the important heterogeneity of assessment methods among studies. The methods used were objective, non-objective, or combined both types. Most studies did not fully describe the data collected: the time since transplantation, the period over which adherence was assessed, the population, the medications, and the threshold discriminating adherence and non-adherence.
Conclusion: The present study found poor medication adherence in the pediatric population post-transplantation. There was a wide range of medication adherence, explained largely by the heterogeneity of assessment methods. Future studies must consider the characteristics of each methodology, but also the threshold defining adherence should be chosen on the basis of clinical outcomes, and describe all data collected to gain precision. To improve adherence in this population, it is essential to identify factors influencing medication (IT and concomitant medications) adherence.
... 5 Medication non-adherence is especially prevalent in adolescent transplant populations with an estimated non-adherence rate of 15%-40%. [6][7][8][9][10] Factors associated with non-adherence in this population are extensive and include low socioeconomic status, family instability, limited parental supervision, depression, poor coping, disease frustration, longer time since transplant, side effects associated with immunosuppressive medication, and poor knowledge about the risks of medication non-adherence. 5,11,12 Researchers have studied numerous direct and indirect methods to assess medication adherence in pediatric patients. ...
... Due to this achievement, long-term problems, the psychological and social aspects of care, the quality of the patient's life, and non-adherence to treatment have become more important. Non-adherence can lead to increased rates of hospitalization, graft loss and death and is well documented following pediatric liver transplant [1][2][3] . Since adolescence is a potentially risky period [4] , this developmental period is challenging for all concerned -young people, parents and health professionals -and lends itself to a high risk for non-adherence in chronic diseases. ...
AIM
To develop a locally adapted, patient-focused transition-program, we evaluated the perceptions of adult and adolescent patients and parents regarding transition-programs and transfer.
METHODS
We evaluated these perceptions by analyzing the responses of pre-transfer adolescents (n = 57), their parents (n = 57) and post-transfer adults (n = 138) from a cohort of pediatric-liver-transplant-patients using a self-designed questionnaire. Furthermore, we compared a responder group with a non-responder group as well as the provided answers with baseline characteristics and clinical outcomes to exclude selection bias, characterize high-risk patients for non-adherence and test for gender differences. Included in our study were all pre-transfer liver transplant and combined liver-kidney transplant recipients aged 11-19 currently under our care and their parents, as well as all post-transfer liver transplant and combined liver-kidney transplant recipients aged ≥ 17 years who had received a liver transplant and were treated at our center during childhood.
RESULTS
Fifty-seven (24 female) pre-transfer patients who received a transplant in the previous 8-186 mo (mean 93.9 mo, median 92 mo, SD 53.8 mo) and 138 (57 female) post-transfer patients who received a transplant in the preceding 2-29 years (mean 15.6 years, median 17, SD 6.90) met the inclusion criteria. A total of 67% of pre-transfer patients (71% of female; 64% of male; P = 0.78) and their parents replied. Additionally, 54% of post-transfer patients (26% of female; 48% of male; P = 0.01) replied. No differences in clinical outcomes were observed between the responder and non-responder groups, and responses did not differ significantly based on clinical complication rates, although they did differ based on gender and the location of medical follow-up after transfer. Adolescents were generally ambivalent toward transition programs. However, adults strongly supported transition programs.
CONCLUSION
Transition programs need to be developed in close collaboration with adolescents. The best clinical practices regarding transition should respect local circumstances, gender and the location of post-transfer medical follow-up.
... 4 The period of transition to adult services is noted as a period of vulnerability or deteriorating health. An example of this is nonadherence to medication being more common in young people 5 and that is exacerbated after transition to adult services. 6 The result of a negative transition experience can undermine previous good practice during pediatric care. ...
Background:
The process and preparation of moving from child to adult services (transition) is a challenging period of time for young people and represents significant changes in care and support systems. The proliferation of mobile phone applications for health purposes suggests that it is an area for further investigation.
Objective:
The review explores the potential to use mobile phone technology to help support young liver transplant recipients moving to adult services. It represents the first review conducted in this specialism and considers a new model of support for young liver patients.
Methods:
A systematic rapid review of the published peer-reviewed literature.
Results:
Two searches were conducted: Search 1: the use of technology to support transition to adult services (6 studies) and Search 2: how best to support liver transplant recipients during transition (6 studies).
Discussion:
Research shows that to achieve positive transition young people need information about their condition and transition. The process needs to be guided by transition readiness, rather than the young persons' age. Although parents and support networks should be in place and are valued, transition should build upon self-management and independence. Results suggest that there appears to be scope to use mobile phone technology to support transition. This is the first time a review has explored the types of issues or concerns facing liver transplant patients and how these can be addressed through mobile phone technology.
... However, in adolescent transplant patients, non-participation in all aspects of the medical regimen including laboratory testing is a prevalent problem associated with adverse consequences. [3][4][5][6][7] The lack of proven interventions requires further studies to address this problem in this high-risk population. ...
Background:
In solid organ transplant patients, non-participation in all aspects of the medical regimen is a prevalent problem associated with adverse consequences particularly in the adolescent and young adult (AYA) age group. This study is the first to evaluate the feasibility, utility and impact of a text messaging (TM) intervention to improve participation in laboratory testing in adolescent liver transplant patients.
Methods:
AYA patients, aged 12 to 21 years, were recruited for a prospective pilot trial evaluating a TM intervention delivered over a 1-year period. The intervention involved automated TM reminders with feedback administered according to a prescribed laboratory testing frequency. Participation rate in laboratory testing after the intervention was compared to the year prior. Patient responses and feedback by text and survey were used to assess feasibility, acceptability and use of the intervention.
Results:
Forty-two patients were recruited and 33 patients remained enrolled for the study duration. Recipients of the TM intervention demonstrated a significant improvement in participation rate in laboratory testing from 58% to 78% (P<.001). This rate was also significantly higher than in non-intervention controls (P=.003). There was a high acceptability, response rate and a significant correlation with reported versus actual completion of laboratory tests by TM.
Conclusions:
TM reminders significantly improved participation in laboratory testing in AYA liver transplant patients. The intervention demonstrated feasibility, acceptability, and use with a high proportion of patients who engaged in and perceived a benefit from using this technology.
... This finding is consistent with the findings from another study on adherence among liver transplant recipients in the US but using a different method of adherence assessment, where the adherence rate was reported to be 61.8%. [33] In general, the rate of medication adherence among adult liver transplant patients ranges from 60% to 85%. The variety of methods used to measure adherence along with the different definitions of the term "non-adherence" may have contributed to the wide range of reported adherence rates in liver transplant recipients. ...
Background/aims:
Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15-100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients.
Patients and methods:
Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant-related data.
Results:
A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 ± 12.7 in Effectiveness, 80.0 ± 25.9 in Side Effects, 83.5 ± 15.7 in Convenience, and 94.6 ± 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 ± 10.4 vs. 88.6 ± 14.8), Side Effects (83.9 ± 22.0 vs. 74.2 ± 30.1), Convenience (87.0 ± 13.9 vs. 77.2 ± 16.1), and Global Satisfaction (96.9 ± 6.6 vs. 91.2 ± 8.6).
Conclusion:
Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients.
... Since SES is typically stable over time, it appears to have ongoing negative consequences, such that lower SES is associated with worse adherence trajectories. It is well-established in the literature that lower SES is associated with poorer adherence among youth with epilepsy [1,12] and other chronic illnesses [32]. Although SES is non-modifiable, clinicians should be aware that it is an important risk factor for non-adherence to AED therapy. ...
This study aimed to identify psychosocial predictors of two-year antiepileptic drug (AED) adherence trajectories among youth with newly diagnosed epilepsy, controlling for known demographic and medical factors.
This study is part of a large, prospective, longitudinal observational study of AED adherence and medical outcomes in youth with newly diagnosed epilepsy. Parents completed questionnaires of psychosocial and family functioning at one month and one year following diagnosis. Chart review and questionnaires were used to collect medical variables and seizure outcomes. Previously established two-year AED adherence trajectories (Severe Early Nonadherence, Variable Nonadherence, Moderate Nonadherence, High Adherence) were used as the outcome variable.
Participants were 91 parents of youth with epilepsy (7.3±2.8years of age; 60% male) and their families. Early (one month following diagnosis) predictors of two-year adherence trajectories included socioeconomic status, epilepsy knowledge, family problem-solving, and family communication. Significant predictors one year following diagnosis included socioeconomic status, parent fears and concerns, and parent life stress.
There are modifiable parent and family variables that predict two-year adherence trajectories above and beyond known medical (e.g., seizures, side effects) factors. Psychosocial interventions delivered at key points during the course of epilepsy treatment could have a positive impact on adherence outcomes.
Copyright © 2015 Elsevier Inc. All rights reserved.
... Many believe that nonadherence to immunosuppressive therapy is the most important factor contributing to poor graft survival among kidney transplant recipients in emerging adulthood (16)(17)(18)(19); poor adherence has been more commonly reported in emerging adults than any other age group (17,20,21). In both pediatric and adult heart recipients, poor adherence has been associated with both late acute rejection and death (22)(23)(24)(25); similar associations between adherence and outcomes have also been observed in other organ types (17,20,21,(26)(27)(28)(29). ...
Emerging adulthood (17-24 years) is a period of high risk for graft failure in kidney transplant. Whether a similar association exists in heart transplant recipients is unknown. We sought to estimate the relative hazards of graft failure at different current ages, compared with patients between 20 and 24 years old. We evaluated 11 473 patients recorded in the Scientific Registry of Transplant Recipients who received a first transplant at <40 years old (1988-2013) and had at least 6 months of graft function. Time-dependent Cox models were used to estimate the association between current age (time-dependent) and failure risk, adjusted for time since transplant and other potential confounders. Failure was defined as death following graft failure or retransplant; observation was censored at death with graft function. There were 2567 failures. Crude age-specific graft failure rates were highest in 21-24 year olds (4.2 per 100 person-years). Compared to individuals with the same time since transplant, 21-24 year olds had significantly higher failure rates than all other age periods except 17-20 years (HR 0.92 [95%CI 0.77, 1.09]) and 25-29 years (0.86 [0.73, 1.03]). Among young first heart transplant recipients, graft failure risks are highest in the period from 17 to 29 years of age.
© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
... Nonadherence to medication is a critical clinical care issue with an estimated cost of $100-300 billion annually 1,2 . Across chronic illness populations, nonadherence is associated with increased disease morbidity [3][4][5][6][7][8] , poorer quality of life and psychological functioning [9][10][11] , higher risk of mortality [12][13][14] , and greater health care utilization 15,16 . Published reports indicate that as many as 50% of children 6 , and 65-88% of adolescents 17,18 , are nonadherent to treatment, increasing the risk of complications substantially. ...
... The model for nonadherence was recognized as being multifactorial including four general groups of elements: health care team and systemrelated factors, condition-related factors, characteristics of therapies and patient-related factors. Much of the research performed has concentrated on organ transplant surgery and chronic conditions such as human immunodeficiency virus (HIV) and tuberculosis since continued adherence is so critical to success and these constitute major health issues in developing countries [6][7][8]. However, adherence to other forms of medical treatment has been studied including hand washing and universal precautions in surgery [9,10]. ...
The success of hand surgery relies heavily on post-operative therapy. The ability to identify barriers to patient adherence with therapy may therefore allow for improvement in therapeutic and surgical decisions and results. The purpose of this study was to identify significant barriers to adherence with hand therapy following surgery for distal radius fracture. A questionnaire addressing demographic, social, psychological, occupational and medical factors was administered to 20 subjects undergoing surgery for distal radius fracture. Adherence was evaluated by the therapist and by the number of missed sessions. There were 9 males and 11 females. Average age was 46.2 (19-88). The therapists' evaluation of adherence and number of missed appointments were significantly correlated (R2 = 0.86, p < 0.0001, Spearman's test). Gender, distance from therapy, and driving status were significantly related to adherence. Difficulty in reaching the therapy sessions was negatively related to adherence with hand therapy in our population. Other parameters such as smoking, were borderline significant. Further study is needed to investigate the effect of additional parameters, in a larger population in order to better define barriers to patient postsurgical adherence.
Background:
The prediction of posttransplant health outcomes for pediatric heart transplantation is critical for risk stratification and high-quality posttransplant care.
Objective:
The purpose of this study was to examine the use of machine learning (ML) models to predict rejection and mortality for pediatric heart transplant recipients.
Methods:
Various ML models were used to predict rejection and mortality at 1, 3, and 5 years after transplantation in pediatric heart transplant recipients using United Network for Organ Sharing data from 1987 to 2019. The variables used for predicting posttransplant outcomes included donor and recipient as well as medical and social factors. We evaluated 7 ML models—extreme gradient boosting (XGBoost), logistic regression, support vector machine, random forest (RF), stochastic gradient descent, multilayer perceptron, and adaptive boosting (AdaBoost)—as well as a deep learning model with 2 hidden layers with 100 neurons and a rectified linear unit (ReLU) activation function followed by batch normalization for each and a classification head with a softmax activation function. We used 10-fold cross-validation to evaluate model performance. Shapley additive explanations (SHAP) values were calculated to estimate the importance of each variable for prediction.
Results:
RF and AdaBoost models were the best-performing algorithms for different prediction windows across outcomes. RF outperformed other ML algorithms in predicting 5 of the 6 outcomes (area under the receiver operating characteristic curve [AUROC] 0.664 and 0.706 for 1-year and 3-year rejection, respectively, and AUROC 0.697, 0.758, and 0.763 for 1-year, 3-year, and 5-year mortality, respectively). AdaBoost achieved the best performance for prediction of 5-year rejection (AUROC 0.705).
Conclusions:
This study demonstrates the comparative utility of ML approaches for modeling posttransplant health outcomes using registry data. ML approaches can identify unique risk factors and their complex relationship with outcomes, thereby identifying patients considered to be at risk and informing the transplant community about the potential of these innovative approaches to improve pediatric care after heart transplantation. Future studies are required to translate the information derived from prediction models to optimize counseling, clinical care, and decision-making within pediatric organ transplant centers.
Background:
Identification of differences in medication adherence by sex or organ type may help in planning interventions to optimize outcomes. We compared immunosuppressive medication adherence between males and females, and between kidney, liver and heart transplant recipients.
Methods:
This multicenter study of prevalent kidney, liver and heart transplant recipients 14-25 years assessed adherence 3 times (0, 3, 6 months post-enrollment) with the BAASIS self-report tool. At each visit, participants were classified as adherent if they missed no doses in the prior 4 weeks and non-adherent otherwise. Adherence was also assessed using the coefficient of variation (CV) of tacrolimus trough levels; CV < 30% was classified as adherent. We used multivariable mixed effects logistic regression models adjusted for potential confounders to compare adherence by sex and by organ.
Results:
Across all visits, males (n = 150, median age 20.4 years, IQR 17.2-23.3) had lower odds of self-reported adherence than females (n = 120, median age 19.8 years, IQR 17.1-22.7) (OR 0.41, 95% CI 0.21-0.80) but higher odds of adherence by tacrolimus CV (OR 2.50, 95% CI 1.30-4.82). No significant differences in adherence (by self-report or tacrolimus CV) were noted between the 184 kidney, 58 liver, and 28 heart recipients.
Conclusion:
Females show better self-reported adherence than males but greater variability in tacrolimus levels. Social desirability bias, more common in females than males, may contribute to better self-reported adherence among females. Higher tacrolimus variability among females may reflect biologic differences in tacrolimus metabolism between males and females rather than sex differences in adherence. There were no significant differences in adherence by organ type.
Background:
AYA who have undergone liver transplantations often struggle to adhere to their post-transplant immunosuppressant medications, which can lead to serious health complications. The objective of this pilot study is to examine the acceptability and feasibility of a brief mobile health (mHealth) intervention and its impact on medication adherence among AYA liver transplant recipients.
Methods:
Thirty-five AYAs (13-21 years old) were randomized to either (1) receive praise text messages whenever laboratory results indicated immunosuppressant medications within the expected range or (2) usual care. Motivation for adherence and adherence were assessed via self-report, and a MLVI was calculated based on values abstracted from the electronic health record.
Results:
Multilevel, multivariate models showed significant associations between group assignment and some self-reported motivation and adherence outcomes but not MLVI. Specifically, AYA receiving the praise text messages were significantly more likely to report taking their prescribed doses (OR = 2.49, p = .03), taking their medicine according to the directions (OR = 2.39, p = .04), and being highly confident in taking their medication (OR = 2.46, p = .04), compared with the usual services group. Qualitative responses indicated praise texts were mostly helpful but could be improved.
Conclusions:
The results suggest texting patients about positive health indicators was acceptable and, with refinement, might promote AYA illness self-management.
Objective:
To analyze demographic, psychosocial and clinical factors in pediatric liver transplant recipients for their association with death or loss to follow-up in adulthood. We aimed to better understand known health disparities in transplant outcomes and identify potentially modifiable risk factors prior to transfer.
Methods:
Retrospective cohort study of children who underwent liver transplantation at a large tertiary transplant center and were transferred to adult care between 2000-2015.
Results:
During the study period 101 qualifying patients were transferred. Ninety-three individuals followed with an adult provider, while eight were lost to follow-up. In total 23/93 patients died after transfer (24.7%). Several childhood factors were associated with adult death: Black race (odds ratio [OR] 6.59, p<0.001); psychiatric illness or substance use (OR 2.81, p=0.04); failure to graduate high school (HS) before transfer (OR 9.59, p<0.001); post-transplant tacrolimus medication level variability index >2.5 (OR 5.36, p=0.04); provider documentation of medication non-adherence (OR 4.72, p=0.02); acute cellular rejection (OR 4.44, p=0.03); presence of diabetes mellitus (OR 5.71, p=0.001) and chronic kidney disease (OR 2.82, p=0.04). Failure to graduate HS was associated with loss to follow-up (p<0.001). On multivariate analysis, Black race, substance use, diabetes, and failure to graduate HS retained association with adult death (each p<0.05).
Conclusions:
Complex, intertwined patient characteristics are associated with increased odds of death in pediatric liver transplant recipients transferred to adult care. Early recognition of high-risk patients and intervention for modifiable factors, such as improved HS graduation and substance use prevention, may improve long-term outcomes.
Objectives:
We analyzed liver tissue morphology dynamics in experimental animals with acute liver failure during treatment with a combination of transplanted cultured embryonic hepatocytes and the hepatoprotective drug Erbisol.
Materials and methods:
We studied 30 white outbred male rats weighing 250 to 350 g, divided into 6 groups with 5 animals in each group. Acute liver damage was induced by a hepatotoxic model of acute liver failure for which carbon tetrachloride was applied (200 μg CCl4/100 g body weight with toxin-to-oil volume ratio of 1:1). To obtain cultured embryonic hepatocytes, we used an enzymatic-mechanical process that caused only minimal cell damage. This method is known to improve the output of viable cultured embryonic hepatocytes, improve the morphological-functional properties of the hepatocytes, and reduce the process time during procurement, and thereby reduce the overall time from procurement to the subsequent culturing of the obtained cells. Transplant of cultured embryonic hepatocytes was performed intrape-ritoneally at a dose of 50 million (0.5 × 108) cells. Morphological studies were performed on day 7 and day 21 of the experiment.
Results and conclusions:
There were significant morphological changes in livers from animals with acute liver failure, caused by widespread necrosis and an elevated inflammatory response. Treatment with injections of cultured embryonic hepatocytes induced regeneration of the liver parenchyma cells and reduced the inflammatory response, both of which were further reduced in rats that received combined treatment of transplant with Erbisol. Combined application of cultured embryonic hepatocytes and Erbisol potentiated the effects of both treatments, which produced intensive proliferation of hepatocytes, hypertrophy and polyploidization of hepatocyte nuclei, and an early restoration of liver structure and organ mass.
“Adherence” is defined as a coincidence of patient’s behaviour and clinical prescriptions, with a cooperative relationship between the patient and the clinician. In the transplant setting, non-adherence can influence short- and long-term outcomes and can negatively impact quality of life (QoL). Aim of this chapter is to provide an exhaustive overview on the themes of adherence and QoL in the liver transplant setting. Particular attention is paid in identifying the principle risk factors of non-adherence and the possible strategies of interventions in order to improve adherence and consequently the QoL.
Background
There is no consensus about long-term outcomes in patients with biliary atresia. We retrospectively reviewed the long-term outcomes in pediatric patients who underwent living donor liver transplantation for biliary atresia.
Methods
Between May 2001 and December 2020, 221 (73%) of 302 pediatric patients who underwent living donor liver transplantation had biliary atresia. The median age at living donor liver transplantation was 1.2 (range 0.2–16.5) years, and follow-up was 10.3 ± 5.5 years.
Results
The 10-year graft survival rates in patients with and without biliary atresia were 94% and 89%, respectively (P = .019). The 10-year graft survival was significantly poorer in patients ≥12 years of age (84%) versus those <12 years of age at living donor liver transplantation (0–2 years: 95%; 2–12 years: 96%) (P = .016). The causes of graft failure in patients with biliary atresia included late-onset refractory rejection (n = 6), bowel perforation (n = 2), and acute encephalitis (n = 2), as well as cerebral hemorrhage, hepatic vein thrombosis, and sepsis (n = 1 for all). All 7 patients with graft failure due to refractory rejection and hepatic vein thrombosis underwent repeated liver transplantation and are alive in 2021. The rates of post-transplant portal vein complications and early-onset acute cellular rejection in patients with biliary atresia were higher than in those without biliary atresia (P = .042 and P = .022, respectively). In 2021, of 60 adolescents with biliary atresia, 14 (23%) reported medication nonadherence. The rate of liver dysfunction due to late-onset acute cellular rejection and graft failure due to late-onset refractory rejection in patients with nonadherence was higher than in patients with satisfactory adherence (P = .009).
Conclusion
The long-term prognosis after living donor liver transplantation in pediatric patients with biliary atresia is quite good. However, long-term support to enhance medication adherence is required in adolescents with biliary atresia.
Objetivo: Fornecer informações ao hepatologista, referentes ao atendimento ao adolescente transplantado, no que diz respeito às questões da adolescência para evitar risco de rejeição, muito prevalente nesse grupo. As informações foram coletadas de artigos científicos publicados nas bases de dados SciELO, MEDLINE e PUBMED de 2004 a 2010, livros técnicos e publicações de consenso de organismos internacionais. Síntese dos dados: Com o aumento do número de transplantes e melhora da sobrevida, muitas crianças transplantadas estão atingindo a fase turbulenta da adolescência e muitos adolescentes são submetidos ao transplante nessa fase. Na atualidade, poucos serviços de transplante têm padronizado um programa de transição, para assegurar ao paciente adolescente um seguimento de saúde adequado após sua transferência para uma clínica de adultos. Alguns autores confirmam que a atenção no período de transição possibilita uma revisão educacional para os pacientes adolescentes e também uma oportunidade conveniente para otimizar o bem-estar na vida adulta. Infelizmente, porém, as clínicas de adultos em geral estão sobrecarregadas de pacientes e as questões do desenvolvimento da adolescência não são prioritárias. O pediatra, que deveria ter um papel essencial na transferência de adolescentes para serviços de saúde de adultos, muitas vezes e de modo inconsciente, acaba atuando como um dificultador por não demonstrar confiança plena em seus colegas. Conclusão: Um ambulatório de transição oferece a oportunidade de abordar questões essenciais para a saúde integral do adolescente transplantado e seu desenvolvimento pleno com temas como: autonomia, identidade, auto-estima, qualidade de vida, sexualidade, alterações corporais, projetos de vida e desenvolvimento da escolaridade/profissionalização.
Solid organ transplantation is now an accepted therapeutic modality for children and teenagers suffering from a wide variety of complex medical conditions. Unfortunately, patients continue to die while on the organ waiting list as there remains an imbalance between the number of recipients listed for transplantation and the number of donors available. The organ allocation process continues to generate ethical questions and debates. In this publication, we discuss some of the most frequently reported ethical matters in the field of pediatric solid organ transplantation.
Background
Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are rare indications for liver transplantation (LT) in children. The aim of the present retrospective multicenter study was to evaluate long-term outcome after LT for autoimmune liver disease in childhood.
Methods
Retrospective data from 30 children who underwent a first LT from 1988 to 2018 were collected.
Results
The study population consisted of 18 girls and 12 boys, transplanted for AIH type 1 (n = 14), AIH type 2 (n = 7) or PSC (n = 9). Mean age at LT was 11.8 ± 5.2 years. The main indications for LT were acute (36.7%) or chronic end-stage liver failure (63.3%). Graft rejection occurred in 19 patients (63.3%); 6 pts required retransplantation for chronic rejection. Recurrence of initial disease was observed in 6 patients (20.0%), all of them with type 1 AIH, after a median time of 42 months, requiring retransplantation in 2 cases. Overall patient survival rates were 96.4%, 84.6%, 74.8%, 68.0%, 68.0%, 68.0% and 68.0% at 1, 5, 10, 15, 20, 25 and 30 years, respectively. Age at LT < 1year (p < 0.0001), LT for fulminant failure (p = 0.023) and LT for type 2 AIH (p = 0.049) were significant predictive factors of death.
Conclusion
Long-term outcome after LT for pediatric autoimmune liver disease is impaired in patients with AIH because of consistent complications such as rejection and disease recurrence.
Purpose:
The purpose of this mixed methods study was to better understand the long term impact of living-related liver donation (LRLD) on youth and young adult (YYA) recipients and their family.
Design and methods:
Semistructured interviews were conducted with YYA, aged 11-18 years, who received a living donation from a parent. Interviews were audiotaped, transcribed, and analyzed to aggregate themes that represented the participants' views as live-liver recipients. An ethnographic process was conducted to understand the participants' social behavior. At interview, participants completed a demographics questionnaire and the Youth Quality of Life Instrument-Research Version (YQOL-R).
Results:
Thirteen adolescents were interviewed; six were re-interviewed as key informants. Three major categories were created from the data: Developing Identity, Redefining Family Relationships, Feeling Gratitude to Donors. The overarching theme was Resiliency. Findings from the YQOL-R showed no difference in overall scores or separate domains when compared with a reference population with no chronic illness.
Conclusion:
Qualitative and quantitative data highlight the positive effect that LRLD can have on pediatric patients as they transition from childhood to adolescence to young adulthood.
Practice implications:
As pediatric transplant centers in the United States soon mark 30 years of performing live-liver donation, recipients are becoming adults and understanding more clearly that the long-term effects of such donations will lead to improvements in future care.
RESUMO Objetivo: Com o sucesso e o aumento do número de transplante hepático, fornecer informações para o médico pediatra para o atendimento do adolescente transplantado de fígado e como ele pode colaborar no que se refere às questões da adolescência e à aderência ao tratamento imunossupressor para evitar o risco de rejeição aguda e crônica com necessidade de retransplante. Fontes dos dados: As informações foram coletadas a partir de artigos científi cos publicados nas bases de dados SciELO, MEDLINE e PUBMED de 2004 a 2010, livros técnicos e publicações de consenso de organismos internacionais. As palavras-chave utilizadas foram: adolescence, solid organ transplantation, adeherence, compliance. Síntese dos dados: Com o aumento do número de transplantes e a melhora da sobrevida, muitas crianças transplantadas estão atingindo a fase turbulenta da adolescência. Os provedores e as próprias crianças que foram submetidas a transplante de órgão sólido experimentam as mesmas difi culdades e frustrações como ocorre com outras doenças graves. Na atualidade ainda existem poucos serviços de transplante que tenham padronizado um programa de transição para assegurar ao paciente adolescente um seguimento de saúde adequado após a sua transferência para uma clínica de adultos. Alguns autores confi rmam que atenção no período de transição possibilita uma revisão educacional para seus pacientes adolescentes e também uma oportunidade conveniente para otimizar o bem-estar na vida adulta. Infelizmente, porém, as clínicas de adultos em geral estão sobrecarregadas de pacientes e as questões do desenvolvimento da adolescência não são prioritárias. O pediatra, que deveria ter o papel essencial na transferência de adolescentes para os serviços de saúde dos adultos, muitas vezes e de modo inconsciente, acaba atuando como um fator difi cultador por não demonstrar confi ança plena em seus colegas. Conclusão: Um ambulatório de transição pode fornecer esta oportunidade por abordar as questões essenciais para saúde integral do adolescente transplantado hepático e o seu desenvolvimento pleno com temas como: autonomia, identidade, auto-estima, qualidade de vida, sexualidade, alterações corporais, projetos de vida e desenvolvimento da escolaridade/profi ssionalização. ABSTRACT Objective: With the number of successful liver transplants rising steadily, this review provides information for pediatricians on the care of adolescents receiving liver transplants, while fostering compliance with immunosuppressive treatment in order to avoid the risk of acute and chronic rejection giving rise to the need for a second transplant, in addition to other important aspects of adolescence. Data Sources: Information was collected from scientifi c articles published in the SciELO, MEDLINE and PubMed databases from 2004 to 2010, as well as technical books and consensus publications by international entities. The descriptors used were: adolescence, solid organ transplantation, adherence, compliance. Findings Summary: As a result of rising numbers of transplants and longer survival times, improvement, many young transplantees are reaching the turbulent
Adult liver transplant programs have heretofore been hesitant to perform liver retransplantation in adult patients who underwent primary liver transplantation as a child (P_A). Areas of concern include: 1) potential disruption in care when transferring from a pediatric to an adult transplant center; 2) generally inferior outcomes of retransplantation; 3) reputation of young adults for non‐adherence to post‐transplant regimen; and 4) potential higher work effort for equivalent outcomes. To examine these concerns, we reviewed data on all U.S. liver adult retransplants from 10/01/1987 to 9/30/2017. We propensity matched the P_A patients to patients who received both primary and retransplantation as adults (A_A), with ≥550 days between transplants. A mixed Cox proportional hazards model with program size and time period of transplantation as random variables revealed that retransplantation of P_A patients produced no significantly different graft survival or patient survival rates than retransplantation of the matched A_A patients. Therefore, inferior rates of liver retransplantation in these patients and concerns about continuity of care in changing transplant programs are not as believed in the wider liver transplant community. In conclusion, liver transplant centers should be optimistic about retransplanting adults who received their primary transplants as children.
To understand factors contributing to liver graft loss and patient death, we queried a national database designed to follow pediatric patients transplanted between 1987 and 1995 till adulthood. A comparison was made to a cohort transplanted between 2000 and 2014. The 5‐, 10‐, 15‐, 20‐, and 25‐year patient survival and graft survival were 95.5%, 93.7%, 89.1%, 80.8%, and 73.1%, and 92.5%, 86.7%, 77.6%, 68.7%, and 62.2%, respectively. The twenty‐year patient/graft survival was significantly worse in those transplanted between 5 and 17 years of age compared to those transplanted at <5 years of age (P < 0.001). For the modern era cohort, the 3‐year patient survival was significantly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5 and 11‐15 years of age (P ≤ 0.02). The 3‐year graft survival was similarly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5, 5‐10, and 11‐15 years of age (P ≤ 0.001). Infection as a cause of death occurred either early or >15 years post‐transplant. Chronic rejection remained the leading cause of graft loss in both cohorts and the commonest indication for retransplantation 20‐25 years following primary transplant. Further research is required to identify modifiable factors contributing to development of chronic rejection.
Purpose
Adherence to the medical regimen after pediatric liver transplantation is crucial for good clinical outcomes. However, the existing literature provides inconsistent evidence regarding the prevalence of and risk factors for nonadherence to the medical regimen after pediatric liver transplantation. This study aimed to investigate such nonadherence after pediatric liver transplantation and risk factors associated with this nonadherence using findings of reported studies.
Methods
The electronic databases of Excerpta Medica, Ovid Technologies, PubMed and WanFang Data were searched using the keywords “adherence”, “liver transplant” and “paediatric”. Additionally, relevant references cited in related studies were used to obtain original articles. Using 22 original articles, data regarding nonadherence to the medical regimen after pediatric liver transplantation were quantitatively combined, and risk factors associated with nonadherence were qualitatively identified. Average rates of nonadherence in four areas of medical regimens were calculated. The heterogeneity of the included original articles was also analyzed. When I²>50 and P<0.05, a random effects model was used; otherwise, a fixed effects model was used. Moreover, Egger’s and Begg’s tests were used to evaluate publication bias, if any, and original articles with P>0.05 were considered to have no publication bias.
Results
The clinical attendance nonadherence rate was 45% (95% confidence interval [CI]: 39–51), global nonadherence rate was 17% (95% CI: 13–21) and immunosuppression non-adherence rates were 39% (95% CI: 26–52) and 34% (95% CI: 30–39) for cyclosporine and tacrolimus, respectively. Risk factors included older age of the pediatric patient, low family cohesion, poor social functioning, poor mental health and single-parent family.
Conclusions
The nonadherence rate in pediatric liver transplantation is high. Therefore, intervention on the basis of risk factors, such as mental health and family function, may be necessary. Moreover, a standard technique for assessing nonadherence to the medical regimen after pediatric liver transplantation, comprising as many dimensions as possible, is required in order to be more objective and comprehensive when assessing nonadherence.
Background:
The period of transition from pediatric to adult services represents a time when young people need support, information, and appropriate care in order to successfully move. It is a period that is associated with nonadherence and disengagement with care.
Objective:
To explore the experiences of young liver transplant recipients transitioning to adult services and determine what they require in order to achieve a successful move. The research also explored the possibility of using a mobile phone application (app) as a tool to support transition.
Design:
Qualitative approach using novel arts-based focus groups and one-to-one interviews.
Participants:
Twenty-one young people aged 16 to 25 years, 16 health-care professionals involved in their care, and 7 young people as follow-up. Participants used services provided by the 3 liver centers in England (Leeds, Birmingham, and London).
Results:
Data highlighted the variability of transition pathways in England for young people moving from child to adult health services. The results showed that they required clear information regarding transition processes including specific medical information and that there was a shortfall in such information. Support was required in the form of a designated transition coordinator or similar specialist who could act as a point of reference and guidance throughout the process. Transitions needed to be individualized and based upon transition readiness rather than age, although the research showed that age cut-offs were still used.
Conclusion:
Young people welcomed apps to provide information, reminders, contacts, and connections. Future research should explore the efficacy of such apps.
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.
Background
Racial disparity in access to liver transplantation among African Americans (AA) compared to Caucasians (CA) has been well described. The aim of this investigation was to examine the presentation of AA liver transplant recipients in a socioeconomically challenged region.
Methods
680 adult liver transplant candidates and 233 resultant recipients between 2007 and 2015 were analyzed using univariate and multivariate analyses to evaluate factors significant for transplantation.
Results
Percentages of wait list patients transplanted were similar between CA and AA (34.9% vs. 32.2%, p = 0.5205). AA were younger (50.4 ± 1.8 vs. 56.3 ± 0.7 yrs, p = 0.0003) with higher average MELD scores (22.9 ± 1.6 vs. 19.4 ± 0.7, p = 0.0230). Overall patient mortality was similar (AA 22.7% vs. CA 26.3%, p = 0.5931). A multiple linear regression showed that male gender was strongly associated with transplantation.
Conclusions
Equal access to liver transplantation remains challenging for racial minorities. At our institution, AA were accepted and transplanted at an equivalent rate as CA despite a higher AA population, HCV rate and diagnosed HCC. AA were younger and sicker at the time of transplant, but overall had similar outcomes compared to CA. Our study highlights the need for studies to delineate the underpinnings of disparity in transplantation access.
Liver allograft rejection has some unique aspects when compared to rejection in other transplanted solid organs. These include a higher current incidence of early rejection episodes but a comparative lack of long-term impact of these early rejection episodes on long-term graft survival. We herein described the clinical presentation of rejection as one possible cause of liver graft dysfunction in two time periods: early (<6 months) and late (?6 months) after transplant. The classification of liver rejection is reinforced and an algorithm is offered to guide the diagnosis and management of liver rejection based upon the post-transplant time period.
This article discusses preliminary findings from phenomenological research into the lived experience of liver transplant recipients in New Zealand, focusing on their views about the organ donor, the donor family, and organ donation more generally. It examines data collected during two phases of research; phase one, comprising seventeen qualitative interviews with transplant recipients across New Zealand, and phase two, which entailed a qualitative survey sent to 180 potential research participants. A brief background to liver transplantation in New Zealand is provided, followed by an outline of the eligibility criteria used to select participants for this research. The perspectives of liver transplant recipients are then explored through the themes of the donated liver as a gift, gratitude, what information recipients have about their donor families, communication with donor families, and conceptions of liver transplantation as a transformative experience.
Purpose: Adherence to immunosuppressants is the key to prevent organ rejection in organ transplant recipients. The purpose of this study was to investigate current interventions to improve adherence to immunosuppressants in liver transplant recipients. Methods: A systemic literature search was done using PubMed, Embase, Cochrane Library, CINAHL and four Korean databases to identify experimental studies reported in English or Korean up to and including 2015. We identified eight intervention studies on the adherence to immunosuppressants in liver transplant recipients independently reviewed by two reviewers. The quality and risk of bias of the selected studies were assessed. Results: Education, conversion of regimen, and text messaging were identified as intervention techniques to improve adherence. We found positive results in three out of four studies implementing educational strategies, but the results were not sufficient to draw a definite conclusion. Conversion from a twice-daily tacrolimus-based regimen to a once-daily tacrolimus extended-release formula was used in three adult-only studies and its effectiveness was confirmed. One study showed that improved adherence and outcomes were effected by using text messaging with pediatric patients. Conclusion: Future research is needed to facilitate interventions to improve adherence to immunosuppressants in various ages of patients including pediatric/adolescent liver transplant recipients.
Solid organ transplantation has become the most effective treatment for end-stage organ failure and is often the unique opportunity for patients to survive. Patients who require organ transplantation do not only face tremendous stressors during the waiting period for transplantation, but also postoperative and during the long-term treatment following transplantation. The burden of psychiatric disorders is significant in patients awaiting and following transplantation and is associated with increased morbidity and mortality. Psychiatric liaison can contribute to appropriate diagnosis and treatment of psychiatric comorbidity and therefore may contribute to improve quality of life of transplant recipients and to the general success of transplantation. Moreover, consulting psychiatrists are often involved in the evaluation of organ recipients and donors. Psychopharmacological treatment following transplantation requires substantive knowledge of pharmacodynamics and pharmacokinetic aspects and adverse effects of immunosuppressant medication and of putative drug-interactions.
Background:
Graft failure risk is highest during emerging adulthood (17-24 years) in kidney and heart transplant. It is unknown whether a similar association exists in liver transplant recipients.
Methods:
We sought to estimate the relative hazards of graft failure at different current ages, compared with those aged 21 to 24 years. We evaluated 17 181 patients recorded in the Scientific Registry of Transplant Recipients who received a first isolated liver transplant at 40 years or younger (1988-2013) and had 6 months or longer of graft function. We used time-dependent Cox models to estimate the association between current age and failure risk, defined as retransplant or death after graft failure; observation was censored at death with graft function.
Results:
There were 2540 failures. Absolute graft failure rates were highest in ages 25 to 29 years (3.0/100 person-years). Compared with individuals with the same time since transplantation, those aged 21 to 24 years had significantly higher failure rates than those younger than 17 years and older than 34 years; hazards did not differ for those aged 25 to 29 years (1.03 [0.86, 1.24]) and were lower, but not significantly, for those aged 17 to 20 years (hazards ratio, 0.83; 95% confidence interval, 0.68-1.01) and ages 30 to 34 years (hazards ratio, 0.84; 95% confidence interval, 0.70-1.01).
Conclusions:
Among young first isolated liver transplant recipients, graft failure risks are highest in the period from 21 to 29 years of age.
AimThis mixed methods study describes the post-transplantation daily life of pre-adolescents and adolescents who had undergone living donor liver transplantation and their parents.Methods
Nine parent–child dyads were enrolled and all children were living donor liver transplant recipients. Three participants were pre-adolescents and the six were adolescents. Five of the parents surveyed in this study had been the donors. Members of the parent–child dyads completed the questionnaires and participated in semistructured interviews. An inductive qualitative analysis of the interview data was conducted.ResultsThe post-transplantation daily life of the parent–child dyads had four distinct patterns: (i) pre-adolescents who had undergone transplantation during infancy, who had no understanding of the transplant procedure, and whose care was managed by their parent(s) without any problems; (ii) adolescents who were aware that their physical condition had improved after the transplant and who managed and dealt with the situation on their own; (iii) adolescents who were dissatisfied with the transplantation and associated immunosuppression because transplant procedures were perceived as negative or because they could not remember the transplant procedure; and (iv) one participant could not be categorized because their liver function deteriorated post-transplantation and they were registered for re-transplantation. Patterns were identified that characterized the post-transplantation daily life of pre-adolescents/adolescents who underwent liver transplantation, and that of their parents. Further research for post-transplantation parent–child dyads is warranted.
Symptoms of posttraumatic stress disorder (PTSD) were described in survivors of life-threatening diseases, the trauma being the experiences associated with the disease or its treatment. Their prevalence in liver transplant recipients is unknown. Based on clinical observations, we hypothesize that a significant proportion of pediatric liver transplant recipients suffers from PTSD symptoms. We further hypothesize that nonadherence (noncompliance) to medical management may, in some cases, be associated with these symptoms. Traumatized patients, according to this hypothesis, will avoid taking their medications, because these serve as painful reminders of the disease.
To determine the prevalence of PTSD symptoms in a sample of pediatric liver transplant recipients. To determine whether symptoms of PTSD are associated with nonadherence in these patients. To describe the clinical presentation of PTSD and the management of severe nonadherence in patients who suffer from this disorder.
Nineteen pediatric liver transplant recipients and their caretakers were interviewed, using the UCLA Post Traumatic Stress Disorder Reaction Index (PTSRI). Data were obtained on a few demographic parameters and perception of disease threat. Adherence was evaluated by 2 methods: 1) a clinician panel (taking into account the clinical sequelae of severe nonadherence); and 2) computation of the standard deviations (SDs) of consecutive determinations of blood levels of Tacrolimus (a higher SD means higher variability between individual measures and is therefore an indicator of nonadherence). As an illustration of the general phenomenon, we describe 3 cases of liver transplant recipients who were nonadherent and who suffered from PTSD.
Six of 19 patients had positive scores on all 3 components of the PTSRI (PTSD patients). Three of these, and none of the others, were considered significantly nonadherent by the panel. Therefore, nonadherence was significantly associated with the existence of symptoms from all 3 domains of PTSD (Fisher's exact test) in our sample. In particular, a high avoidance score on the PTSRI was highly correlated with panel-determined nonadherence. Further, SD of medication levels were significantly higher in PTSD patients, compared with the rest of our sample. No significant differences were found in perception of disease threat or demographic variables between PTSD patients and the rest of our sample. The 3 cases that we describe became adherent to their medications when symptoms of PTSD subsided during the course of therapy.
Clinically significant nonadherence, determined by 2 different methods, was associated with the full spectrum of PTSD symptoms in this sample. It was especially associated with a high avoidance score, which suggests that avoidance of reminders of the disease (eg, medications) may be a mechanism of nonadherence. Screening for and management of these symptoms, therefore, may improve adherence. This novel concept may be applicable to other patient populations. However, more data are needed before any definite conclusions can be drawn.
To understand the impact of family structure on the metabolic control of children with diabetes, we posed two research questions: 1) what are the differences in sociodemographic, family, and community factors between single-mother and two-parent families of diabetic children? and 2) to what extent do these psychosocial factors predict metabolic control among diabetic children from single-mother and two-parent families?
This cross-sectional study included 155 diabetic children and their mothers or other female caregivers. The children were recruited if they had been diagnosed with diabetes for at least 1 year, had no other comorbid chronic illnesses, and were younger than 18 years of age. Interviews and self-report questionnaires were used to assess individual, family, and community variables.
The findings indicate that diabetic children from single-mother families have poorer metabolic control than do children from two-parent families. Regression models of children's metabolic control from single-mother families indicate that age and missed clinic appointments predicted HbA1c levels; however, among two-parent families, children's ethnicity and adherence to their medication regimen significantly predicted metabolic control.
This study suggests that children from single-mother families are at risk of poorer metabolic control and that these families have more challenges to face when raising a child with a chronic illness. Implications point to a need for developing strategies sensitive to the challenges of single mothers.
This longitudinal pilot study of adolescent renal transplant recipients (a) describes the prevalence of psychological distress, (b) describes the prevalence of nonadherence, and (c) explores the association between the recipient's psychological distress and his/her subsequent medical adherence. Twenty-two adolescents, aged 13-18 years, completed two interviews that were separated by approximately 12 months. Psychological distress was assessed in three domains: symptoms of depression, anxiety, and anger. Adherence was assessed in three domains: medication taking, blood work, and clinic attendance. At the initial interview, 36.4% had symptoms of depression, 36.4% endorsed anxiety, and 18.2% endorsed excessive state anger. Non-adherence rates were 13.6% for medication, 22.7% for blood work, and 50% for missed clinic. At the second interview, nonadherence with medication remained the same and the other domains decreased. Our small pilot sample, however, limited our ability to detect statistically significant changes over time. Predictive analyses demonstrated that adolescents with excessive anger were at greater risk for subsequently missing medications than adolescents without excessive anger. These findings suggest that while symptoms of depression and anxiety are observed among some adolescents with renal transplants, only anger is associated with elevated risk for nonadherence with medication.
Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated.
We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days.
An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited.
Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.
: Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate.
Despite the fact that non-adherence to medical therapy is one of the major causes of late morbidity and mortality in pediatric liver transplant recipients, little is known of the risk factors involved in this behavior. Three cases of fatal non-adherence are reported. Factors associated with non-adherence were investigated by performing a retrospective chart review of a panel of 27 variables in an age-matched cohort of 15 pediatric liver transplant recipients. The most striking differences between the severely non-adherent group and the age-matched cohort included history of substance abuse, child abuse (physical or sexual), not having two parents at home, having received public assistance, having been diagnosed with a psychiatric disorder, and history of school dropout. In addition it appeared that a pretransplant diagnosis of autoimmune hepatitis was associated with more significant medical sequelae related to non-adherence. These findings are preliminary owing to the retrospective design of this study, but could be used as a starting point for a prospective study of this important phenomenon.
Inadequate compliance with prescribed medication regimens in children is complex and poorly understood. We measured the
extent and pattern of noncompliance with cyclosporine in our adolescent renal transplant population and attempted to determine
factors associated with poor compliance. After informed consent, each patient was provided cyclosporine capsules in a medication
bottle equipped with an electronic monitoring device (MEMS-4) in the lid. Of the 24 patients eligible, 19 patients (8 female,
11 male) completed the study. Four (21%) patients took less than 80% of the prescribed cyclosporine doses. Five (26%) patients
took drug holidays involving ≥3 consecutive doses. There was a trend towards improved compliance with the evening dose (88.5%
vs. 93.4%, P = 0.09) and a downward trend in compliance over the course of the study (P = 0.17). None of the variables tested were found to be associated with noncompliance. Experienced physicians and nurses were
able to identify 2 of the 4 individuals who were identified by MEMS as noncompliant. Additionally, 2 of the 4 noncompliant
patients demonstrated low cyclosporine trough levels (<50 ng/ml). Noncompliance with cyclosporine regimens occurs commonly
in adolescent renal transplant recipients. Unexpectedly low cyclosporine levels are strongly suggestive of noncompliance,
whereas other variables, including prediction by physicians and nurses intimately involved in the care, were not reflective
of noncompliance.
Noncompliance with medication and follow-up care was evaluated in 538 renal, 50 heart, and 13 liver transplant recipients. In a retrospective review of 260 kidney transplant recipients followed from three months posttransplant, the incidence of medication noncompliance was 18%. It was 15% in a prospective study of 196 kidney recipients from 1984 to 1987. Patients most likely to become noncompliant were young and in a lower socioeconomic group. There was no significant difference in the incidence of noncompliance with respect to cadaveric vs. living-related donor kidney source, or in male vs. female patients. There was a higher incidence of noncompliance in blacks and Hispanics, but that may have been due to a higher incidence of lower socioeconomic status in those groups. Noncompliance can occur many years posttransplant and was seen in heart and liver transplant recipients. In the retrospective study, 91% of kidney transplant recipients who were noncompliant with medications and follow-up care either lost their grafts or died. Noncompliant behavior was usually not predictable and was often without an identifiable reason. Efforts to increase compliance, such as better patient selection, more education, and simplified medical regimens may have reduced the incidence of noncompliance in recent patients.
Noncompliance with medication and follow-up care was evaluated in 538 renal, 50 heart, and 13 liver transplant recipients. In a retrospective review of 260 kidney transplant recipients followed from three months posttransplant, the incidence of medication non-compliance was 18%. It was 15% in a prospective study of 196 kidney recipients from 1984 to 1987. Patients most likely to become noncompliant were young and in a lower socioeconomic group. There was no significant difference in the incidence of noncompliance with respect to cadaveric vs. living-related donor kidney source, or in male vs. female patients. There was a higher incidence of noncompliance in blacks and His-panics, but that may have been due to a higher incidence of lower socioeconomic status in those groups. Noncompliance can occur many years posttransplant and was seen in heart and liver transplant recipients. In the retrospective study, 91 % of kidney transplant recipients who were noncompliant with medications and follow-up care either lost their grafts or died. Noncompliant behavior was usually not predictable and was often without an identifiable reason. Efforts to increase compliance, such as better patient selection, more education, and simplified medical regimens may have reduced the incidence of noncompliance in recent patients.
(C) Williams & Wilkins 1990. All Rights Reserved.
Noncompliance in the adolescent is a difficult problem that can be prevented or improved. It is best identified early by nonjudgmental questioning about current or previous regimen behavior. An appreciation of the relevant psychological and social issues can suggest to the clinician which adolescents are at high risk for noncompliance. Intervention techniques based on educational and psychological principles can be successfully applied by the physician to improve compliance and can improve the teenager's sense of mastery. Personal characteristics of the physician, however, may determine whether he or she can work productively with the noncompliant adolescent.
In summary, compliance behavior among adolescents is complex and imcompletely understood. Although the study of compliance is important for understanding the adolescent's stage of psychological development, relationships with authority figures, and the beginning of the youngster's career as a consumer of health care, its ultimate importance lies in the prospect of improving the likelihood that medication will be utilized appropriately. The first step in the process involves systematic monitoring of compliance rather than doing so only when noncompliance is clinically suspected. When compliance is found to be problematic for an adolescent, resorting to "scare" techniques or re-education is rarely effective. A more positive outcome may be achieved by determining the circumstances under which the youngster was successful in complying and attempting to tailor-make the regimen accordingly. Barriers to compliance, such as the presence of side effects, previous negative experience with the medicine, and lack of conviction about the diagnosis of appropriateness of therapy, should always be explored. Other potential intervention strategies for improving compliance have been discussed. In the final analysis, however, as Jonson has noted, all strategies aimed at improving compliance must provide the patient with insight into his own situation and himself, as well as his capability of doing something other than conforming when he judges it best.
Noncompliance is known to be an important cause of late graft failure after renal transplantation. We investigated prospectively the degree of compliance with immunosuppressive and antihypertensive drugs during the first year after renal transplantation by monthly pill counts. In addition, we examined whether noncompliance was related to a number of demographic and clinical variables or to the occurrence of rejections. The study population consisted of 127 patients who were involved in a randomized trial comparing cyclosporine monotherapy with azathioprine-prednisone treatment. Average compliance rates approximated 100%, although considerable variability within and between subjects was observed. Using an arbitrary limit to classify patients as compliers or noncompliers, the following frequencies of noncompliance were observed during the study year: cyclosporine, 23%; azathioprine, 13%; prednisone, 23%; atenolol, 36%; and nifedipine, 32%. Average compliance scores for all immunosuppressive drugs were superior to those of antihypertensive medication (P < 0.001). Except for a better compliance for prednisone in men as compared with women, we found no consistent relationship between compliance on the one hand and several demographic variables, graft function, or quality of life on the other hand. Patients who developed one or more acute rejection episodes showed a higher degree of undercompliance, especially for prednisone, than patients without rejections (P < 0.01). Following the occurrence of a rejection episode, compliance scores improved significantly. Keeping in mind the limitations of the pill count method, we conclude that noncompliance with immunosuppressive drugs is not a huge problem during the first year after renal transplantation. However, it is likely that noncompliance contributes to a certain number of acute rejection episodes.
The purpose of this study was to identify variables that are associated with noncompliance among adult renal transplant recipients, including demographic characteristics, transplant-related variables, and psychosocial factors. The measurement of noncompliance was improved by assessing noncompliant behaviors (i.e., noncompliance with medications and the follow-up regimen) prior to the onset of complications and/or graft loss and by measuring compliance as a continuous rather than dichotomous variable. Two-hundred-and-forty-one renal transplant recipients completed the Beck Depression Inventory, the anxiety and hostility subscales of the Brief Symptom Inventory, the Multidimensional Health Locus of Control Scale, the Inventory of Socially Supportive Behaviors, the Coping Strategies Inventory, a measure of transplant-related stressors, and self-report measures of compliance with medications and the follow-up regimen. Approximately half of our sample reported at least some degree of noncompliance. Recipients who were younger, female, unmarried, retransplanted, and with lower incomes tended to be noncompliant with medications (all p's < 0.05). Recipients who were unmarried, low income, not insulin-dependent, and with a longer time since transplant tended to be noncompliant with the follow-up regimen. In addition, recipients who reported higher stress and more depression, who coped with stress by using avoidant coping strategies, and who believed that health outcomes are beyond their control were less compliant with both medications and follow-up (all p's < 0.05). Regression analyses revealed that stress was the strongest predictor of both medication and follow-up compliance.
In this descriptive cross-sectional study, we investigated the incidence, determinants, and consequences of subclinical noncompliance with immunosuppressive therapy in 150 adult renal transplant recipients with more than one year posttransplant status. Symptom frequency and symptom distress, and self-care agency were measured by the Transplant Symptom Frequency and Symptom Distress Scale, and the Appraisal for Self-Care Agency Scale, respectively. The Long-Term Medication Behavior Self-Efficacy Scale and a renal transplant knowledge questionnaire were developed as part of this study to measure perceived self-efficacy and knowledge of the therapeutic regimen. Demographic variables were also measured. The incidence of subclinical noncompliance with immunosuppressive therapy as assessed by interview was 22.3%. Compliers and noncompliers differed significantly on the variables of marital status (P = 0.03), situational-operational knowledge (P = 0.02), self-care agency (P = 0.03), and perceived self-efficacy related to long-term medication intake (P = 0.048). A logistic regression model using gender, marital status, perceived self-efficacy, self-care agency, knowledge about medication administration and signs of infection, and situational operational knowledge as predictor variables, revealed a 78.6% correct classification of compliers versus noncompliers and a sensitivity ratio of 95.9%. There were significantly more acute late rejection episodes (P = 0.003) in the noncompliant group. Graft survival at 5 years in this group was also significantly lower (P = 0.03) than the compliant patients. No significant difference was found in terms of the occurrence of chronic rejection episodes or in terms of patient survival at 5 years. Because noncompliance is a risk factor for negative clinical outcome in renal transplant recipients, it is of utmost importance to develop intervention strategies to enhance compliance in this population by using determinants identified in exploratory studies.
Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate.
Kidney transplantation is a successful treatment for end-stage renal disease. We studied demographic and psychosocial variables that relate to compliance behaviors following renal transplant. One hundred and five renal allograft recipients, with a minimum of 18 months follow-up, were studied. A biographical questionnaire, the Center for Epidemiologic Studies Depression Scale, the Multidimensional Health Locus of Control Scale, and the Social Support Appraisals Questionnaire were used as measuring instruments. Specifically for this study, we designed a Health Belief Model Questionnaire, a Patient and Provider Relationship Questionnaire, a Compliance Self-Report Questionnaire, and a Self-Efficacy Questionnaire. Compliance was determined by cyclosporine whole blood levels > 30 ng/ml, maintenance of ideal body weight (< 20% gain), and percentage of missed clinic visits (< 20%). Data was analyzed using discriminant analysis, Pearson's correlation, and chi-square. Four groups were identified, i.e., overall compliant (n = 25), noncompliant with diet (n = 29), noncompliant with medication (n = 27), and overall noncompliant (n = 29). No patient missed > 20% of clinic visits. Discriminant function analysis distinguished patients who were compliant from those who were not. Males were more likely to be noncompliant with medication, whereas females were more likely to be noncompliant with diet. Noncompliance was also associated with increased numbers of prescribed medications, depression, black race, locus of control attributed to powerful others, unemployment, as well as the perceived amount of social and family support. Patients with failed grafts (n = 14) were more depressed (P < 0.05), perceived less benefit from the treatment regimen (P < 0.01), and had less confidence in their care providers (P < 0.05) than those recipients of successful grafts (n = 91). In conclusion, this study identifies a number of psychosocial and demographic variables that impact on patient compliance behaviors after renal transplant. Interventional strategies to obviate noncompliance will need to consider these heterogeneous variables in order to maximize long-term renal allograft survival.
Although noncompliance with immunosuppressive medication is recognized as a critical behavioral risk factor for late acute rejection episodes and graft loss after transplantation, little is known about the degree of subclinical cyclosporine noncompliance, its associated risk for acute late rejection episodes (>1 year after transplantation), and its determinants in heart transplant recipients.
The convenience sample of this longitudinal study included 101 European heart transplant recipients (87 men and 14 women), with a median age of 56 (Q1 = 50, Q3 = 61) and a median posttransplantation status of 3 (range 1 to 6) years. Subclinical cyclosporine noncompliance was measured during a 3-month period with electronic event monitoring. Selected sociodemographic, behavioral, cognitive, emotional, health, and treatment-related determinants of medication noncompliance were measured by using instruments with established psychometric properties or by patient interviews. With the use of iterative partitioning methods of cluster analysis, including nonstandardized electronic event monitoring compliance parameters, patients were categorized by degree of subclinical cyclosporine noncompliance into a 3-cluster solution.
Overall compliance was high, with a median medication taking compliance of 99.4%. The 3 derived clusters, that is, excellent compliers (84%), minor subclinical noncompliers (7%), and moderate subclinical noncompliers (9%), differed significantly by degree of subclinical noncompliance (p < .0001) and showed a 1.19%, 14.28%, and 22.22% incidence of late acute rejections (p = .01), respectively. The 3 groups also differed in terms of former medication noncompliance (p = .02), appointment noncompliance (p = .03), and perceived self-efficacy with medication taking (p = .04).
Although in absolute numbers cyclosporine compliance in this sample was high, minor deviations from dosing schedule were associated with an increased risk for acute late rejection episodes. This suggests a pivotal role of patient compliance in successful long-term outcome after transplantation.
Despite the fact that non-adherence to medical therapy is one of the major causes of late morbidity and mortality in pediatric liver transplant recipients, little is known of the risk factors involved in this behavior. Three cases of fatal non-adherence are reported. Factors associated with non-adherence were investigated by performing a retrospective chart review of a panel of 27 variables in an age-matched cohort of 15 pediatric liver transplant recipients. The most striking differences between the severely non-adherent group and the age-matched cohort included history of substance abuse, child abuse (physical or sexual), not having two parents at home, having received public assistance, having been diagnosed with a psychiatric disorder, and history of school dropout. In addition it appeared that a pretransplant diagnosis of autoimmune hepatitis was associated with more significant medical sequelae related to non-adherence. These findings are preliminary owing to the retrospective design of this study, but could be used as a starting point for a prospective study of this important phenomenon.
Many studies confirm that noncompliance or poor compliance is one of the great problems in health care as it results in waste of resources and funds.
This overview includes literature on heart, liver, and kidney transplants with emphasis on heart transplantation in adult and pediatric transplant patients and addresses the following variables as potential predictors of postoperative compliance problems: demographic variables (age, marital status, gender) psychological variables (anxiety, denial) psychiatric disorders (major depression, anxiety, and personality disorders), poor social support, pretransplant noncompliance, obesity, substance abuse, and health-related variables (distance from transplant center, indication for transplantation, required pretransplant assist device). Relevant studies on these topics that were conducted up to 1999 are included and discussed in this overview. The most important results are presented in tables.
Unfortunately, there has not been any systematic and comprehensive review of the literature on predictors of noncompliance in organ transplant patients so far. With organ transplantation noncompliance impairs both life quality and life span as it is a major risk factor for graft rejection episodes and is responsible for up to 25% of deaths after the initial recovery period. Therefore, it might be assumed that well-informed transplant patients are a highly motivated group whose compliance is just as high. This is not the case. However, even when graft loss means loss of life as in heart or liver transplantation, noncompliance occurs. To best select potential organ recipients, it would be ideal if patients who are very likely to show noncompliant behavior could be identified already before being transplanted.
The literature overview shows the necessity of preoperative psychosocial screening regarding predictors for posttransplant noncompliance.
The consequences of failing to comply to doctor's instructions can be damaging and devastating for the individual patient and their family. Noncompliance also leads to waste, as it reduces the potential benefits of therapy, and to the extra cost of treating avoidable consequent morbidity. Life-long immunosuppression is a prerequisite for good graft function, and noncompliance is often associated with late acute rejection episodes, graft loss, and death. It might be assumed that transplant patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. This overview includes literature on heart, liver, and kidney transplants in adult and pediatric transplant patients. Compliance behavior after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, and reasons for postoperative noncompliance will be addressed.
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.
Although non‐compliance in pediatric liver transplants is known to be a major cause of late graft loss and patient mortality, follow‐up seems inconsistent. As liver transplant becomes a luxury because of the shortage of organs, the need to maximize graft and patient survival by intense monitoring becomes a necessity. When evaluating children with elevated liver enzymes post‐transplant, early or late non‐compliance should always be suspected. The risk of non‐compliance in children with chronic illness varies from 10 to 89%. In a study by Sudan et al. (Annals of Surgery 1997: 29: 430–431) non‐compliance was one of the leading causes of late mortality in children age 10–17 yr. Although it is well documented that teenagers have a high rate of non‐compliance, the rate in the younger children has not been documented. In our series, we found that parental non‐compliance comprises the majority of our problems with liver dysfunction, hospitalization, and graft loss.
The purpose of this study was to evaluate the incidence of non‐compliance in children post‐liver transplant. A retrospective chart review of patient records from admissions and outpatient records was performed for documentation of elevated enzymes and low immunosuppressive levels. From July 1987 to December 2002, our program performed 266 liver transplants in 234 children, with 1‐yr graft survival of 84% and 1‐yr patient survival of 90%. Our overall patient survival was 85% with 77% graft survival. There were 40 children with documented non‐compliance with mild to severe liver dysfunction in this study. Twenty‐eight of these children were younger than 10 yr [28 of 40 (46%) <5 yr], and 12 (30%) were older than 10 yr at the time of rejection. In 10 of 40 children, there was one documented incident of non‐compliance, while 26 of 40 had two to four incidents, and four had five or more documented events. Our children (50%) came from two‐parent households. The remaining 50% were from single households. In 27 of 40 (68%) children, rejection was confirmed by liver biopsy. In children on cyclosporine (Neoral; Novartis, East Hanover, NJ, USA) with a known history of non‐compliance and low immunosuppressive levels, C2 monitoring was performed to verify absorption. Admission for drug monitoring and verification of non‐compliance was accomplished in 32 of 40 (80%). Four of the 40 children (10%) were retransplanted, and one child had died.
In conclusion, non‐adherence to medications remains a major source of graft loss and morbidity post‐transplant. We found that non‐compliance crosses all socio‐economic and cultural groups and that flexibility of clinic hours, shortened time between visits, and decreased numbers and times of medication will increase adherence.
Solid organ transplantation has become accepted therapy for the treatment of end-stage organ dysfunction in children. As early management of the pediatric transplant recipient has improved, important age-related differences in long-term patient outcomes have become apparent. Late morbidity and mortality can, in most cases, be attributed to the consequences of long-term immunosuppression: graft loss from under-immunosuppression or an increased incidence of cancer, hypertension, renal failure or diabetes from over-immunosuppression. Age-related differences in both biological and psychological factors play an important role in the optimization of therapy in the transplanted child. Important age-related differences have been demonstrated in all phases of pharmacokinetics: absorption, distribution, metabolism and elimination. Information regarding specific age-related pharmacokinetic differences is lacking for many immunosuppressive medications. Further study using physiologically based pharmacokinetic (PBPK) models will lead to more specific recommendations for age-based immunosuppression protocols. Non-adherence is common among solid organ transplant recipients of all ages and the consequences of non-adherence include increased rejection, late graft loss and death. The biological and psychological developmental changes that occur during adolescence place the transplanted adolescent at an even higher risk of non-adherence and poor outcome than other age groups. Further studies to elucidate the importance of both age-related pharmacokinetic and behavioral factors are needed to formulate therapeutic interventions that would improve adherence and patient outcomes.
Recent advancements in immunosuppression and surgical techniques have significantly improved the outcome of kidney transplantation in the pediatric population. Adolescents enjoy the best 1-year graft survival of any age group. However, the long-term transplant outcome in adolescents is disappointing. Non-adherence with immunosuppressive medications is one of the most important contributing factors for graft rejection and loss in teenagers. The impact of non-adherence is perceived to be far more powerful in adolescent transplant recipients than in the transplant population as a whole. To better understand adolescent non-adherence, the process of transplantation must be placed in the context of adolescent development. Adolescents try to establish their identity and autonomy separately from the parents; however at the same time, adolescents with chronic illness require help, support and guidance from adults, including parents and medical personnel. Adolescents have limited ability to anticipate abstractly the long-term consequences of their immediate actions. This inconsistency can create frustration in both adolescents and in the supporting systems around them. Despite the significant consequences of adolescent non-adherence, research in this area is scarce. There are still no established definitions, standardized diagnostic methods and effective interventions to treat and prevent this problem. We propose the recommendations to approach the problems of adolescent transplant non-adherence from the transplant clinician's viewpoint. With early identification and appropriate interventions, significant improvement in adolescent graft survival is possible.
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.
By definition, tolerance will eliminate the problem of adolescent medication non-adherence. Although adolescents' propensity toward non-adherence makes them at first glance to be particularly attractive candidates for tolerance trials, there are also immunologic, psychosocial and ethical barriers that temper enthusiasm for their inclusion at present. Limits in emotional and cognitive maturity are combined during the teenage years with adult-like immunologic maturity to lessen the potential for successful implementation of tolerance and near tolerance strategies. Alternatively, an interval step to tolerance in adolescents is to eliminate the medications most likely contributing to non-adherence through harsh side effects such as steroids and calcineurin inhibitors. This manuscript will review the general topic of transplantation tolerance with specific attention given to the application of pro-tolerant therapies in adolescent recipients.
Advances in knowledge in transplantation have improved 1-year renal allograft survival in all age groups of pediatric patients. However, the results from many studies have shown that the long-term allograft survival is least successful in adolescent recipients. The major cause of late graft failure in adolescents can be contributed in large measure to medication noncompliance. Medication noncompliance in teenagers has been shown to be more than four times greater in adolescents than in adults. The teenage years are a time of transition from childhood to adulthood. Important tasks during this transition include the development of an autonomous identity that progresses to full independence. However, the cognitive skills and intellectual maturation of adolescents are still limited, and this is particularly true in adolescents with chronic diseases. They have difficulty with abstract thinking, particularly the conceptualization of future consequences of present actions. This leads to characteristic risk-taking behaviors, including noncompliance with medical treatments. This transition is more intricate for adolescents with chronic illness because of their physical limitations. There are a number of strategies that are helpful in mitigating noncompliance. Adolescents must be dealt with directly. Previous noncompliant behaviors need to be acknowledged and dealt with, because studies show that noncompliance is a "stable" personality attribute that persists over time. Efforts should be made to choose medications that have the least side effects. Psychological and psychiatric conditions such as posttraumatic stress disorder require early recognition, diagnosis, and treatment. It is necessary to build rapport with teenagers, and this should start before transplantation. A multidisciplinary approach with physicians, social workers, nurses, and transplant coordinators is an effective mean of enhancing compliance. These and other strategies outlined in this discussion will enable the adolescent to achieve good compliance rates and prevent graft loss.