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.

Impact of Surgical Complexity on Health-Related Quality of Life in Congenital Heart Disease Surgical Survivors.

BACKGROUND: Surgical complexity and related morbidities may affect long-term patient quality of life (QOL). Aristotle Basic Complexity (ABC) score and Risk Adjustment in Congenital Heart Surgery (RACHS-1) category stratify the complexity of pediatric cardiac operations. The purpose of this study was to examine the relationship between surgical complexity and QOL and to investigate other demographic and clinical variables that might explain variation in QOL in pediatric cardiac surgical survivors. METHODS AND RESULTS: Pediatric Cardiac Quality of Life (PCQLI) study participants who had undergone cardiac surgery were included. The PCQLI database provided sample characteristics and QOL scores. Surgical complexity was defined by the highest ABC raw score or RACHS-1 category. Relationships among surgical complexity and demographic, clinical, and QOL variables were assessed using ordinary least squares regression. A total of 1416 patient-parent pairs were included. Although higher ABC scores and RACHS-1 categories were associated with lower QOL scores (P<0.005), correlation with QOL scores was poor to fair (r=-0.10 to -0.29) for all groups. Ordinary least squares regression showed weak association with R(2)=0.06 to R(2)=0.28. After accounting for single-ventricle anatomy, number of doctor visits, and time since last hospitalization, surgical complexity scores added no additional explanation to the variance in QOL scores. CONCLUSIONS: ABC scores and RACHS-1 categories are useful tools for morbidity and mortality predictions prior to cardiac surgery and quality of care initiatives but are minimally helpful in predicting a child's or adolescent's long-term QOL scores. Further studies are warranted to determine other predictors of QOL variation.

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.

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 reveals highly variable adherence patterns in patients prescribed ivacaftor.

BACKGROUND: Previous studies of CF treatments have shown suboptimal adherence, though little has been reported regarding adherence patterns to ivacaftor. Electronic monitoring (EM) of adherence is considered a gold standard of measurement. METHODS: Adherence rates by EM were prospectively obtained and patterns over time were analyzed. EM-derived adherence rates were compared to pharmacy refill history and self-report. RESULTS: 12 subjects (age 6-48 years; CFTR-G551D mutation) previously prescribed ivacaftor were monitored for a mean of 118 days. Overall adherence by EM was 61% (SD=28%) and decreased over time. Median duration between doses was 16.9 hours (IQR 13.9-24.1 hours) and increased over time. There was no correlation between EM-derived adherence and either refill history (84%, r=0.26, p=0.42) or self-report (100%, r=0.40, p=0.22). CONCLUSIONS: Despite the promising nature of ivacaftor, our data suggest adherence rates are suboptimal and comparable to other prescribed CF therapies, and more commonly used assessments of adherence may be unreliable.

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.

Communication about the risks and benefits of phase I pediatric oncology trials.

INTRODUCTION: Phase 1 pediatric oncology trials offer only a small chance of direct benefit and may have significant risks and an impact on quality of life. To date, research has not examined discussions of risks and benefits during informed consent conferences for phase 1 pediatric oncology trials. The objective of the current study was to examine clinician and family communication about risks, benefits, and quality of life during informed consent conferences for phase 1 pediatric oncology trials. METHODS: Participants included clinician investigators, parents, and children recruited from 6 sites conducting phase 1 pediatric oncology trials. Eighty-five informed consent conferences were observed and audiotaped. Trained coders assessed discussions of risks, benefits, and quality of life. Types of risks discussed were coded (e.g., unanticipated risks, digestive system risks, and death). Types of benefits were categorized as therapeutic (e.g., discussion of how participation may or may not directly benefit child), psychological, bridge to future trial, and altruism. RESULTS: Risks and benefits were discussed in 95% and 88% of informed consent conferences, respectively. Therapeutic benefit was the most frequently discussed benefit. The impact of trial participation on quality of life was discussed in the majority (88%) of informed consent conferences. CONCLUSION: Therapeutic benefit, risks, and quality of life were frequently discussed. The range of information discussed during informed consent conferences suggests the need for considering a staged process of informed consent for phase 1 pediatric oncology trials.

Quality of life in pediatric patients affected by electrophysiologic disease.

BACKGROUND: Treatment of electrophysiologic (EP) disease in pediatric patients has improved; however, the effects on quality of life (QOL) are unknown. OBJECTIVE: The purpose of this study was to compare QOL within EP disease groups and to other congenital heart diseases, to evaluate the effects of cardiac rhythm devices on QOL, and to identify drivers of QOL in EP disease. METHODS: Cross-sectional study of patient/parent proxy-reported Pediatric Cardiac Quality of Life Inventory scores (Total, Disease Impact, Psychosocial Impact) in subjects aged 8 to 18 years from 11 centers with congenital complete heart block (CCHB), ventricular tachycardia (VT), supraventricular tachycardia (SVT), and long QT syndrome (LQTS). QOL was compared between EP disease groups and congenital heart disease groups [bicuspid aortic valve (BAV), tetralogy of Fallot (TOF), and Fontan]. General linear modeling was used to perform group comparisons and to identify predictors of QOL variation. RESULTS: Among 288 patient-parent pairs, mean age was 12.8 ± 3.0 years. CCHB (µ = 83) showed higher patient Total QOL than other EP disease cohorts (P ≤ .02; LQTS µ = 73; SVT µ = 74). SVT (µ = 75) and LQTS (µ = 75) had lower patient Total scores than BAV (µ = 81; P ≤ .008). Patient/parent-proxy QOL scores for all EP disease groups were not different than TOF and higher than Fontan. The presence of a cardiac rhythm device was associated with lower QOL scores in LQTS (µ = 66 vs µ = 76; P < .01). Predictors of lower patient/parent-proxy QOL included EP disease type (P ≤ .03), increased medical care utilization (P ≤ .04), and no parental college degree (P ≤ .001). CONCLUSION: Given the significant variation in QOL in EP disease type, stratification by EP disease type and increased medical care utilization may allow for targeted interventions to improve QOL.

Family hardships and serum cotinine in children with asthma.

BACKGROUND AND OBJECTIVE: A better understanding of how poverty-related hardships affect child health could highlight remediable intervention targets. Tobacco smoke exposure may be 1 such consequence of family hardship. Our objective was to explore the relationship between family hardships and tobacco exposure, as measured by serum cotinine, a tobacco metabolite, among children hospitalized for asthma. METHODS: We prospectively enrolled a cohort of 774 children, aged 1 to 16 years, admitted for asthma or bronchodilator-responsive wheezing. The primary outcome was detectable serum cotinine. We assessed family hardships, including 11 financial and social variables, through a survey of the child's caregiver. We used logistic regression to evaluate associations between family hardship and detectable cotinine. RESULTS: We had complete study data for 675 children; 57% were African American, and 74% were enrolled in Medicaid. In total, 56% of children had detectable cotinine. More than 80% of families reported ≥ 1 hardship, and 41% reported ≥ 4 hardships. Greater numbers of hardships were associated with greater odds of having detectable cotinine. Compared with children in families with no hardships, those in families with ≥ 4 hardships had 3.7-fold (95% confidence interval, 2.0-7.0) greater odds of having detectable serum cotinine in adjusted analyses. Lower parental income and educational attainment were also independently associated with detectable serum cotinine. CONCLUSIONS: Family hardships are prevalent and associated with detectable serum cotinine level among children with asthma. Family hardships and tobacco smoke exposure may be possible targets for interventions to reduce health disparities.

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.

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.

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.

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.

Autonomy support and responsibility-sharing predict blood glucose monitoring frequency among youth with diabetes.

OBJECTIVE: Adolescence poses a number of special challenges for youth and their families managing the Type 1 diabetes medical regimen. Little is known on how family and youth factors and management of the regimen change over the course of early adolescence and predict adherence to the regimen during this developmental period. METHODS: Youth with Type 1 diabetes (n = 239) and their maternal caregivers completed measures of diabetes-specific autonomy support, diabetes-related family conflict, regimen responsibility, and blood glucose monitoring frequency (BGMF) at 4 timepoints over a 3-year period. RESULTS: Autonomy support and BGMF significantly decreased over time and responsibility for the diabetes regimen shifted from the caregiver toward youth over time. Significant changes in perceived family conflict over time differed depending on the reporter. Baseline BGMF, changes in caregiver autonomy support, and changes in responsibility for the regimen significantly predicted changes in BGMF over time. CONCLUSIONS: This study documents changes in autonomy support, youth responsibility for the diabetes regimen, and BGMF during the transition into early adolescence. Higher levels of caregiver autonomy support preserve BGMF during a developmental period in which BGMF typically deteriorates.

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.

Identification and prediction of group-based glycemic control trajectories during the transition to adolescence.

OBJECTIVE: To identify trajectories of glycemic control over a period of 3 years in a pediatric sample of youth diagnosed with Type 1 diabetes transitioning to adolescence. A second aim was to examine a set of modifiable individual and family level baseline predictors of glycemic control group membership. METHODS: This multisite, prospective study included 239 children and adolescents (ages 9-11 years at baseline) diagnosed with Type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c (HbA1c) collected at 6-month intervals over a period of 3 years. Predictors of glycemic control membership included baseline global executive functioning, diabetes self-management, diabetes-specific family conflict, blood glucose monitoring frequency, and relevant individual and family level covariates. RESULTS: Group-based trajectory analyses were used to describe patterns of glycemic control from baseline to 36 months and 3 trajectories were identified: low risk (42.9%), elevated risk (44.6%), and high risk (12.1%) subgroups. Baseline maternal-reported family conflict, blood glucose monitoring frequency, and gender were significant predictors of glycemic control group membership. Higher levels of baseline family conflict, lower frequency of blood glucose monitoring, and female gender were associated with elevated and high-risk group membership. CONCLUSIONS: These findings underscore the importance of examining trajectories of HbA1c across time. These results suggest that problematic trajectories of glycemic control are evident during the transition to adolescence. Furthermore, there are modifiable individual and family level characteristics that predict group membership and hence could be targeted in interventions to ensure adequate glycemic control is maintained over time and that risks for diabetes-related complications are reduced.

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.

Strategies of adherence promotion in the management of pediatric chronic conditions.

Children and families often have difficulty following prescribed medical treatment for chronic pediatric conditions. Such nonadherence has a significant impact on children's health care outcomes and the costs of their care. This review describes a comprehensive approach to increase treatment adherence in chronic pediatric illnesses and lessen its impact. Key elements of this proposed model of adherence promotion include the following: (1) a core approach to adherence promotion to be implemented by pediatric health care providers; (2) follow-up and ongoing management; and (3) tailoring and targeting specific more intensive family-centered interventions to children and adolescents who demonstrate clinically significant treatment nonadherence or risk for nonadherence. Behavioral specialists have important roles in conducting research on adherence promotion, training health care providers, and delivering services to children and adolescents with clinically significant adherence problems.

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.