Dennis Drotar’s research while affiliated with Cincinnati Children's Hospital Medical Center and other places

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.

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.

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.

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.

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. 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. 12 subjects (age 6-48years; CFTR-G551D mutation) previously prescribed ivacaftor were monitored for a mean of 118days. Overall adherence by EM was 61%(SD=28%) and decreased over time. Median duration between doses was 16.9hours (IQR 13.9-24.1hours) 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). 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. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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. 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. 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. 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. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.

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.

Treatment for electrophysiologic diseases (EPD) in pediatric patients has improved. Effects on quality of life (QOL) are unknown. 1) To compare QOL within EPD groups and to other congenital heart diseases (CHD); 2) To evaluate effects of cardiac rhythm devices (CRD) on QOL; 3) To identify drivers of QOL in EPD. Cross-sectional study of patient/parent proxy-reported Pediatric Cardiac Quality of Life Inventory (PCQLI) scores (Total, Disease Impact (DI), Psychosocial Impact (PI)) in subjects 8-18 years from 11 centers with congenital heart block (CCHB), ventricular tachycardia (VT), supraventricular tachycardia (SVT), and long QT syndrome (LQTS). QOL was compared between EPD groups and CHD groups [bicuspid aortic valve (BAV), tetralogy of Fallot (TOF) and Fontan]. General linear modeling (GLM) was used to perform group comparisons and identify predictors of QOL variation. Among 288 patient-parent pairs, mean age was 12.8+3.0 years. CCHB (μ =83) showed higher patient Total QOL than other EPD cohorts (p<0.02; LQTS μ=73; SVT μ =74). SVT (μ =75) and LQTS (μ =75) had lower patient Total scores than BAV (μ =81; p<0.008). Patient/parent-proxy QOL scores for all EPD groups were not different than TOF and higher than Fontan. The presence of CRDs was associated with lower QOL scores in LQTS (μ =66 vs. μ =76; p<0.01). Predictors of lower patient/parent-proxy QOL included EPD type (p<0.03), increased medical care utilization (p<0.04), and no parental college degree (p<0.001). Given significant variation in QOL in EPD type, stratification by EPD type and increased medical care utilization may allow for targeted interventions to improve QOL. Copyright © 2015. Published by Elsevier Inc.