Measuring Medication Adherence in Pediatric Cancer: An Approach to Validation.

Objective: This study described the prospective relationship between pharmacological and behavioral measures of 6-mercaptopurine (6MP) medication adherence in a multisite cohort of pediatric patients diagnosed with cancer ( N = 139). Methods: Pharmacological measures (i.e., metabolite concentrations) assessed 6MP intake. Behavioral measures (e.g., electronic monitoring) described adherence patterns over time. Results: Three metabolite profiles were identified across 15 months: one group demonstrated low levels of both metabolites (40.8%) consistent with nonadherence and/or suboptimal therapy; two other groups demonstrated metabolite clusters indicative of adequate adherence (59.2%). Those patients whose metabolite profile demonstrated low levels of both metabolites had consistently lower behavioral adherence rates. Conclusions: To our knowledge, this was the first study to prospectively validate a pharmacological measure of medication adherence with a behavioral adherence measure in a relatively large sample of pediatric patients with cancer. Using multiple methods of adherence measurement could inform clinical care and target patients in need of intervention.

Executive Functioning and School Performance among Pediatric Survivors of Complex Congenital Heart Disease.

OBJECTIVE: To investigate the presence and severity of real-world impairments in executive functioning-responsible for children's regulatory skills (metacognition, behavioral regulation)-and its potential impact on school performance among pediatric survivors of complex congenital heart disease (CHD). STUDY DESIGN: Survivors of complex CHD aged 8-16 years (n = 143) and their parents/guardians from a regional CHD survivor registry participated (81% participation rate). Parents completed proxy measures of executive functioning, school competency, and school-related quality of life (QOL). Patients also completed a measure of school QOL and underwent IQ testing. Patients were categorized into 2 groups based on heart lesion complexity: 2-ventricle or single-ventricle. RESULTS: Survivors of complex CHD performed significantly worse than norms for executive functioning, IQ, school competency, and school QOL. Metacognition was more severely affected than behavioral regulation, and metacognitive deficits were more often present in older children. Even after taking into account demographic factors, disease severity, and IQ, metacognition uniquely and strongly predicted poorer school performance. In exploratory analyses, patients with single-ventricle lesions were rated as having lower school competency and school QOL, and patients with 2-ventricle lesions were rated as having poorer behavioral regulation. CONCLUSIONS: Survivors of complex CHD experience greater executive functioning difficulties than healthy peers, with metacognition particularly impacted and particularly relevant for day-to-day school performance. Especially in older children, clinicians should watch for metacognitive deficits, such as problems with organization, planning, self-monitoring, and follow-through on tasks.

Practical communication guidance to improve phase 1 informed consent conversations and decision-making in pediatric oncology.

BACKGROUND: It can be difficult to explain pediatric phase 1 oncology trials to families of children with refractory cancer. Parents may misunderstand the information presented to them, and physicians may assume that certain topics are covered in the informed consent document and need not be discussed. Communication models can help to ensure effective discussions. METHODS: Suggestions for improving the informed consent process were first solicited from phase 1 study clinicians via questionnaire. Eight parents who had enrolled their child on a phase 1 pediatric oncology trial were recruited for an advisory group designed to assess the clinicians' suggestions and make additional recommendations for improving informed consent for pediatric phase 1 trials. RESULTS: A phase 1 communication model was designed to incorporate the suggestions of clinicians and families. It focused on educating parents/families about phase 1 trials at specific time points during a child's illness, but specifically at the point of disease recurrence. An informative phase 1 fact sheet that can be distributed to families was also presented. CONCLUSIONS: Families who will be offered information regarding phase 1 clinical trials can first receive a standardized fact sheet explaining the general purpose of these early-phase clinical trials. Parental understanding may be enhanced further when oncologists address key themes, beginning at the time of diagnosis and continuing through important decision points during the child's illness. This model should be prospectively evaluated.

Historical analysis in pediatric psychology: from gaining access to leading.

OBJECTIVE: To provide a historical analysis of professional growth and the legacy of early challenges to the development of the field of pediatric psychology: METHOD: More than 40 years of professional experience and consideration of published work provided the basis for this article. RESULTS: Challenges to the future of pediatric psychology that date back to the origins of the field include foundational challenges involving medical authority and administrative control as well as models of medical practice in pediatric hospital settings. These influences limited opportunities for program leadership and independent funding of clinical services, constrained interorganizational organization, and led to an underemphasis of prevention and primary care in clinical practice, research, and training. CONCLUSION: Transformative future growth in pediatric psychology will necessitate innovative strategies that address continuing professional challenges with roots in the field's early history.

A 3-year prospective study of parent-child communication in early adolescents with type 1 diabetes: relationship to adherence and glycemic control.

OBJECTIVE: To examine changes in parent-child communication patterns and their relation to glycemic control and treatment adherence using observational data in a 3-year prospective multisite study of youth with type 1 diabetes aged 9-11 years at baseline and their families (n = 217). METHODS: Adolescents and caregivers participated in a diabetes problem-solving discussion. Families were rated on negative and positive communication and interactions using the Interaction Behavior Code. RESULTS: Maternal and paternal negative communication decreased over time, whereas adolescent and maternal positive communication and positive reciprocity increased. Baseline preadolescent youth and maternal positive communication predicted adherence 3 years later. Changes in family communication did not predict changes in glycemic control or adherence. CONCLUSIONS: During the transition to adolescence, family communication changed in unexpected and positive ways. Additionally, the relationship of baseline family communication to subsequent adherence suggests the need to assess family communication concerning diabetes-related management during preadolescence.

Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework.

OBJECTIVES: This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). METHODS: This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. RESULTS: Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. CONCLUSIONS: Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood.

Electronic monitoring of medication adherence in early maintenance phase treatment for pediatric leukemia and lymphoma: identifying patterns of nonadherence.

OBJECTIVE: To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). METHODS: Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7-19 years diagnosed with ALL or LBL across 6 centers. RESULTS: The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. CONCLUSIONS: Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns.

Health-related quality of life outcomes in children and adolescents with congenital heart disease.

OBJECTIVES: To compare health-related quality of life (HRQOL) in a group of pediatric patients with congenital heart disease (CHD) and healthy controls and patients with other chronic diseases, and to compare HRQOL among patients with CHD of various severity categories with one another, with controls, and with patients with other chronic diseases. STUDY DESIGN: In this cross-sectional survey, t tests were used to compare patient and proxy-reported Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) scores (including total, physical health, and psychosocial health summary scores) in children (aged 8-12 years) and adolescents (aged 13-18 years) between controls and (1) a composite CHD population; and (2) patients in each of 3 CHD severity categories: mild (no intervention), biventricle (BV; postintervention), and single ventricle (SV; postpalliation). PedsQL scores among CHD severity categories were compared by ANOVA. PedsQL scores were also compared in the CHD population and children with other chronic diseases without age stratification using t tests. RESULTS: There were 1138 (children, n = 625; adolescents, n = 513) and 771 (children, n = 528; adolescents, n = 243) patient and/or proxy reporters in the CHD and healthy control groups, respectively. Total, physical health, and psychosocial health summary scores were lower in the composite CHD, BV, and SV groups compared with controls (P < .0001). There were significant differences among disease severity categories for all scores (P < .01). The composite CHD, BV, and SV groups had similar PedsQL scores as end-stage renal disease, asthma, and obesity populations. CONCLUSION: Children and adolescents with BV and SV CHD have significantly lower HRQOL than healthy controls and similar HRQOL as patients with other chronic pediatric diseases. Interventions targeting both physical and psychosocial domains are needed to improve HRQOL in this high-risk population.

Patient involvement in informed consent for pediatric phase I cancer research.

OBJECTIVE: To examine children's and adolescents' involvement in the informed consent conference for phase I cancer trials and test associations with patient age, ease of understanding, and pressure to participate. PROCEDURE: Participants included 61 patients aged 7 through 21 years who were offered participation in a phase I trial. Consent conferences were audiotaped, transcribed, and coded for communication between patients and physicians and between patients and parents. RESULTS: On the basis of word counts, the mean proportion of the consent conference in which the physician was talking to the patient was 36%; the vast majority (73%) of this communication consisted of giving information. Physician-patient communication increased with age, but overall levels of patient-to-physician communication were low (3%). After controlling for patient age, greater physician-to-patient communication was associated with greater ease of understanding. CONCLUSIONS: The focus on providing information in the context of informed consent may come at the expense of other communication exchanges that are important to patients, especially in the context of end-of-life decisions. Children and adolescents may benefit from the assent process when physicians direct more of their communication to them. Future research should identify the reasons for low patient communication during the consent conference and strategies to enhance their participation in decision making about phase I trial enrollment.

Patterns and predictors of paternal involvement in early adolescents' type 1 diabetes management over 3 years.

OBJECTIVE: To document trajectories of paternal involvement in diabetes management and examine bidirectional associations with diabetes outcomes across early adolescence. METHODS: 3-year prospective assessment of paternal involvement, diabetes self-management, and glycemic control among 136 youth (age 9-12 at baseline) and their mothers and fathers. RESULTS: Unconditional growth curves demonstrated decreasing amount (maternal report: F(1,128) = 14.79; paternal report: F(1,111) = 12.95, ps < 0.01) and level of contribution (maternal report: F(1,131) = 23.6, p < .01) of paternal involvement. Controlling for covariates, lower youth self-management predicted an increasing slope in fathers' self-reported amount of involvement (b = -0.15 to -0.22, p < .05), and higher levels of fathers' self-reported level of contribution predicted a decreasing slope in youths' self-reported self-management (b = -0.01, p < .05). CONCLUSIONS: Like mothers, fathers' involvement declines modestly during early adolescence. Different aspects of paternal involvement influence or are influenced by youths' self-management. Communication about ways to enhance fathers' involvement before this transition may help prevent or reduce declining diabetes management and control common in adolescence.

Suggestions from adolescents, young adults, and parents for improving informed consent in phase 1 pediatric oncology trials.

BACKGROUND: Informed consent for a pediatric oncology phase 1 trial is a delicate process, and is made more complex by the difficulty of the information and the requirement for parental consent, and patient assent when applicable. This analysis identifies suggestions for improving the informed consent process received from parents and adolescent and young adult patients (aged 14 years-21 years) who had the option of participating in a phase 1 pediatric oncology trial. METHODS: A total of 57 parents and 20 patients completed interviews as part of a multisite, prospective, descriptive study. These transcribed interviews were studied using established content analysis methods. RESULTS: Parent and patient responses contained 220 suggestions and 54 suggestions, respectively. A total of 21 unique suggestions for improvement emerged in 3 main themes: 1) provision of more information; 2) structure and presentation of the informed consent process, and 3) suggestions for physicians conducting the process. Common suggestions included providing more specific information about the trial, allowing more time for decision-making, and using different methods to deliver information. CONCLUSIONS: Participants involved in the informed consent process for a phase 1 trial provided specific recommendations to research teams to enhance the process. Physician/investigators should be informed of these recommendations and develop and test interventions incorporating them.

Prevalence and patterns of retention in cardiac care in young adults with congenital heart disease.

The population with adult congenital heart disease is expanding. Cardiac care retention and follow-up patterns were assessed in 153 adults with congenital heart disease (median age, 24.5 years), previously compliant as teenagers. The majority (125; 81.7%) were retained in care, most often by a pediatric cardiologist (69%). The rate of retention was surprisingly high.

A meta-analysis of adherence to antiretroviral therapy and virologic responses in HIV-infected children, adolescents, and young adults.

The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) <100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and may be affected by moderating sample and methodological factors. Methodological and research recommendations for the interpretation of the current findings as well as for future HIV adherence related research are presented.

Adolescent perspectives on phase I cancer research.

BACKGROUND: The aim of this study was to examine adolescent patients' perspectives on their understanding and decision making about a pediatric phase I cancer study. PROCEDURE: Participants included adolescents ages 14-21 years with cancer (N = 20), all of whom attended a phase I study consent conference. Participants responded to closed- and open-ended questions on a verbally administered structured interview, which assessed aspects of understanding and decision making about the phase I study. RESULTS: All participants decided to enroll in the phase I study. The majority of participants understood that participation was voluntary, entailed risks, and that they could withdraw. Most also believed that participation in the phase I study would increase the length of their lives. The most frequent reasons for enrolling were positive clinical benefit, needing an option, impact on quality of life, and few side effects or fewer than those of current or past treatments. Eighty-five percent of participants reported that they themselves made the final decision about enrollment in the phase I study. CONCLUSIONS: Most participants hoped or expected that the phase I study would provide a direct benefit (increased survival time or cure) and reported that they themselves were the final decision-maker about enrollment. Clinicians may underestimate the role of adolescents, especially if they believe that parents typically make such decisions. Future research should assess the actual participation of children and adolescents during the informed consent process and explore the role of hope in their decision making about phase I studies.

The impact of socio-economic status on health related quality of life for children and adolescents with heart disease.

BACKGROUND: Socioeconomic status (SES) is known to influence children's health-related quality of life. Many SES indicators assess distinct dimensions of a family's position rather than measuring the same underlying construct. Many researchers, however, see SES indicators as interchangeable. The primary aim of this study was to determine which measure of SES had the strongest impact on health-related quality of life. METHODS: This is a secondary analysis of the Pediatric Cardiac Quality of Life Inventory Validation Study. The SES variables were family income, Hollingshead Index (occupational prestige), and highest parent educational attainment level. Health-related quality of life was measured using the Pediatric Cardiac Quality of Life Inventory. Correlations tested the relationship among the three SES indicators. Regression-based modeling was used to calculate the strength of the association between SES measures and the Pediatric Cardiac Quality of Life Inventory. RESULTS: The correlations among the SES measures were moderately high, with the correlation between the Hollingshead Index and parental education being r = 0.62 (95% CI = 0.56-0.65). There were equally high correlations between family income and the Hollingshead (r = 0.61, 95% CI = 0.57-0.65) and a slightly lower correlation between family income and parental education (r = 0.55, 95% CI = 0.52-0.59). Family income had the highest explanatory value compared to the Hollingshead Index or parental educational attainment, while controlling for sex, race, current cardiac status, and original diagnosis, accounting for 4-5% of the variation in patient and parent Pediatric Cardiac Quality of Life Inventory Total score, respectively, compared to the other SES measures. CONCLUSION: Family income as an SES measure demonstrated the greatest fidelity with respect to health-related quality of life as measured by the Pediatric Cardiac Quality of Life Inventory across respondent groups and explained more of the variation compared to the Hollingshead Index or highest parental educational attainment.

Reflections on developing collaborative research in pediatric psychology: implications and future directions.

OBJECTIVES: Collaborative research with pediatric colleagues has become increasingly important in the professional agenda of pediatric psychology, and there is a continuing need to articulate the challenges of such research. To address this need, this article describes types of collaborative research, reasons for collaboration, collaborative process, challenges, and strategies to facilitate collaborative research. METHODS: Experiences and lessons learned over the course of a career in collaborative research are described. RESULTS: Challenges in collaborative research can be overcome by effective strategies of engagement and communication. Useful methods of training researchers in collaborative research include modeling and supervised mentored experiences in research initiated by trainees. CONCLUSION: Data are needed to identify the characteristics of successful collaborative research, strategies to promote effective research, and methods of training and career development.

Clinical effectiveness of comprehensive psychological intervention for nonadherence to medical treatment: a case series.

OBJECTIVE: To evaluate the effectiveness of an adherence promotion intervention provided to patients and families referred to a clinical service. METHODS: 6 patients and their caregivers representing 5 different chronic conditions were seen for comprehensive psychological intervention that was evaluated based on electronic monitoring of adherence to prescribed oral medication. RESULTS: Time series analysis (Auto-Regressive Integrated Moving Average) indicated that for each of the 6 cases, treatment adherence increased during the intervention phase relative to nonintervention periods, but for 5 of these 6 patients, adherence decreased during the follow-up period (p < .05). CONCLUSION: Comprehensive adherence promotion strategies delivered in standard clinical practice were effective, but the effects did not persist after treatment. Future adherence promotion interventions should focus on sustaining intervention effects.

Changes in executive functioning and self-management in adolescents with type 1 diabetes: a growth curve analysis.

OBJECTIVE: To investigate the relation of changes in executive functioning to changes in diabetes self-management in a 2-year prospective study of a sample of youth aged 9-11 years at baseline (n = 239) with type 1 diabetes and their maternal caregivers. RESEARCH DESIGN AND METHODS: Youth and maternal caregivers completed the Diabetes Self-Management Profile (DSMP) at baseline, 12 months, and 24 months. Maternal caregivers completed the Behavioral Rating Inventory of Executive Functioning (BRIEF) at the same time points to assess global executive functioning, and the domains of behavioral regulation and metacognition. RESULTS: Youth reported self-management decreased over time (p < .01) while behavioral regulation (e.g., the child's ability to shift cognitive set and moderate emotions and behaviors via emotional control) increased (p < .05). Changes in behavioral regulation significantly predicted rate of change in youth-reported self-management (p < .01). Global executive functioning and metacognition (e.g., the child's ability to monitor, initiate, plan, organize, and sustain future-oriented problem solving and working memory) did not change over time and did not predict changes in self-management. Moreover, executive functioning and self-management did not predict changes in HbA1c. CONCLUSIONS: Positive changes in behavioral regulation may enhance self-management of type 1 diabetes during the transition to adolescence.

Diabetes management and glycemic control in youth with type 1 diabetes: test of a predictive model.

The objective of this study was to test a comprehensive model of biologic (pubertal status), family (communication and conflict), and psychological influences (behavioral autonomy) on diabetes management and glycemic control in a sample of youth (N = 226) with type 1 diabetes recruited during late childhood/early adolescence (ages 9-11 years). The study design was a prospective, multisite, multi-method study involving prediction of diabetes management and glycemic control 1 year post-baseline. The primary outcome measures included diabetes management behaviors based on the Diabetes Self-Management Profile (DSMP) administered separately to mothers and youth and glycemic control measured by glycated hemoglobin (HbA1c) obtained by blood samples and analyzed by a central laboratory to ensure standardization. Our hypothesized predictive model received partial support based on structural equation modeling analyses. Family conflict predicted less adequate glycemic control 1 year later (p < 0.05). Higher conflict predicted less adequate diabetes management and less adequate glycemic control. More advanced pubertal status also predicted less adequate glycemic control, but behavioral autonomy did not. Family conflict is an important, potentially clinically significant influence on glycemic control that should be considered in primary and secondary prevention in the management of type 1 diabetes in youth.

Diabetes self-management profile short form: a preliminary report.

Effective family management of type 1 diabetes in childhood is critical to maintaining optimal glycemic control. The purpose of this study was to provide preliminary evidence for a reduced form of the Diabetes Self-Management Profile (DSMP) using Rasch modeling techniques. The study was a secondary analysis of DSMP data drawn from a previous study on patterns of self-management from 239 preadolescents with type 1 diabetes. Rasch modeling strategies were used to identify the most informative items and then a reduced score composite was correlated with hemoglobin A1c (A1c) and blood glucose monitoring (BGM) frequency. A short form of the DSMP was obtained using seven items that comprised all five subscales of the DSMP. The DSMP Short-Form (DSMP-SF) composite score correlated significantly with child's HbA1c and BGM frequency. The DSMP-SF may be considered a valid and effective screening interview alternative to the longer, original, DSMP, particularly when attempting to identify high-risk patients.