Joseph R. Rausch

Patterns of nonadherence to antiepileptic drug therapy in children with newly diagnosed epilepsy.

CONTEXT Because of epilepsys common occurrence, the narrow therapeutic and safety margins of antiepileptic medications, and the recognized complications of medication nonadherence in adults with epilepsy, identifying the rates, patterns, and predictors of nonadherence in children with epilepsy is imperative. The onset and evolution of antiepileptic drug nonadherence in children with newly diagnosed epilepsy remains unknown. OBJECTIVES To identify and characterize trajectories of adherence in children with newly diagnosed epilepsy over the first 6 months of therapy and to determine sociodemographic and epilepsy-specific predictors of adherence trajectories. DESIGN, SETTING, AND PATIENTS Prospective, longitudinal observational study of antiepileptic drug adherence in a consecutive cohort of 124 children (2-12 years old) with newly diagnosed epilepsy at Cincinnati Childrens Hospital Medical Center. Patients were recruited from April 2006 through March 2009, and final data collection occurred in September 2009. MAIN OUTCOME MEASURE Objective adherence measured using electronic monitors. RESULTS Fifty-eight percent of children with newly diagnosed epilepsy demonstrated persistent nonadherence during the first 6 months of therapy. Group-based trajectory models identified 5 differential adherence patterns (Bayesian information criterion = -23611.8): severe early nonadherence (13%; 95% confidence interval [CI], 8%-20%), severe delayed nonadherence (7%; 95% CI, 3%-12%), moderate nonadherence (13%; 95% CI, 8%-20%), mild nonadherence (26%; 95% CI, 19%-34%), and near-perfect adherence (42%; 95% CI, 33%-50%). The adherence pattern of most patients was established by the first month of therapy. Socioeconomic status was the sole predictor of adherence trajectory group status (χ(4)(2) = 19.3 [n = 115]; P < .001; partial r(2) = 0.25), with lower socioeconomic status associated with higher nonadherence. CONCLUSION Five trajectory patterns were identified that captured the spectrum of nonadherence to antiepileptic drugs among children with newly diagnosed epilepsy; the patterns were significantly associated with socioeconomic status.

Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents A Randomized Clinical Trial

IMPORTANCE Early, safe, effective, and durable evidence-based interventions for children and adolescents with chronic migraine do not exist. OBJECTIVE To determine the benefits of cognitive behavioral therapy (CBT) when combined with amitriptyline vs headache education plus amitriptyline. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial of 135 youth (79% female) aged 10 to 17 years diagnosed with chronic migraine (≥15 days with headache/month) and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to the CBT plus amitriptyline group (n = 64) or the headache education plus amitriptyline group (n = 71). The study was conducted in the Headache Center at Cincinnati Childrens Hospital between October 2006 and September 2012; 129 completed 20-week follow-up and 124 completed 12-month follow-up. INTERVENTIONS Ten CBT vs 10 headache education sessions involving equivalent time and therapist attention. Each group received 1 mg/kg/d of amitriptyline and a 20-week end point visit. In addition, follow-up visits were conducted at 3, 6, 9, and 12 months. MAIN OUTCOMES AND MEASURES The primary end point was days with headache and the secondary end point was PedMIDAS (disability score range: 0-240 points; 0-10 for little to none, 11-30 for mild, 31-50 for moderate, >50 for severe); both end points were determined at 20 weeks. Durability was examined over the 12-month follow-up period. Clinical significance was measured by a 50% or greater reduction in days with headache and a disability score in the mild to none range (<20 points). RESULTS At baseline, there were a mean (SD) of 21 (5) days with headache per 28 days and the mean (SD) PedMIDAS was 68 (32) points. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group vs 6.8 for the headache education plus amitriptyline group (difference, 4.7 [95% CI, 1.7-7.7] days; P = .002). The PedMIDAS decreased by 52.7 points for the CBT group vs 38.6 points for the headache education group (difference, 14.1 [95% CI, 3.3-24.9] points; P = .01). In the CBT group, 66% had a 50% or greater reduction in headache days vs 36% in the headache education group (odds ratio, 3.5 [95% CI, 1.7-7.2]; P < .001). At 12-month follow-up, 86% of the CBT group had a 50% or greater reduction in headache days vs 69% of the headache education group; 88% of the CBT group had a PedMIDAS of less than 20 points vs 76% of the headache education group. Measured treatment credibility and integrity was high for both groups. CONCLUSIONS AND RELEVANCE Among young persons with chronic migraine, the use of CBT plus amitriptyline resulted in greater reductions in days with headache and migraine-related disability compared with use of headache education plus amitriptyline. These findings support the efficacy of CBT in the treatment of chronic migraine in children and adolescents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00389038.

a Pilot Randomized Controlled Trial of a Clinic and Home-Based Behavioral Intervention to Decrease Obesity in Preschoolers

We evaluated the efficacy of a 6‐month clinic and home‐based behavioral intervention (Learning about Activity and Understanding Nutrition for Child Health; LAUNCH) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced standard of care (Pediatrician Counseling; PC). LAUNCH was a family‐based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves. PC presented the same diet and activity recommendations, but was delivered in a one‐time PC session. Eighteen children aged 2–5 years (mean 4.71 ± 1.01) with an average BMI percentile of 98 (±1.60) and an overweight parent were randomized to LAUNCH or PC. Assessments were conducted at baseline, 6 months (end of LAUNCH treatment) and 12 months (6 months following LAUNCH treatment). LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 (post‐treatment) BMI z (−0.59 ± 0.17), BMI percentile (−2.4 ± 1.0), and weight gain (−2.7 kg ± 1.2) than PC and this difference was maintained at follow‐up (month 12). LAUNCH parents also had a significantly greater weight loss (−5.5 kg ± 0.9) at month 6 and 12 (−8.0 kg ± 3.5) than PC parents. Based on the data from this small sample, an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care.

Changes in Treatment Adherence and Glycemic Control During the Transition to Adolescence in Type 1 Diabetes

OBJECTIVE To test models of unidirectional and bidirectional change between treatment adherence and glycemic control in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a 2-year longitudinal, multisite study of 225 youth with type 1 diabetes recruited at the cusp of adolescence (aged 9–11 years) to describe the mutual influences of glycemic control as measured by HbA1c and treatment adherence as measured by blood glucose monitoring frequency (BGMF) during the transition to adolescence. RESULTS HbA1c increased from 8.2 to 8.6% (P < 0.001) and BGMF decreased from 4.9 to 4.5 checks per day (P < 0.02) during the 2-year period. Changes in the BGMF slope predicted changes in HbA1c. A change (increase) in HbA1c was associated with a change (decrease) in BGMF of 1.26 (P < 0.001) after controlling for covariates. CONCLUSIONS The magnitude of the effect of declining treatment adherence (BGMF) on glycemic control in young adolescents may be even greater than declines observed among older adolescents. BGMF offers a powerful tool for targeted management of glycemic control for type 1 diabetes during the critical transition to adolescence.

Prevalence, Patterns, and Persistence of Sleep Problems in the First 3 Years of Life

OBJECTIVE: Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life. METHODS: Three hundred fifty-nine mother/child pairs participated in a prospective birth cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring. RESULTS: Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6–24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24–36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life. CONCLUSIONS: Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.

Depressive symptoms predict change in glycemic control in adolescents with type 1 diabetes: rates, magnitude, and moderators of change.

Hood KK, Rausch JR, Dolan LM. Depressive symptoms predict change in glycemic control in adolescents with type 1 diabetes: rates, magnitude, and moderators of change.

Treatment Factors Affecting Longitudinal Quality of Life in New Onset Pediatric Epilepsy

OBJECTIVES Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. METHOD Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. RESULTS HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. CONCLUSIONS AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

Parent and family stress factors predict health-related quality in pediatric patients with new-onset epilepsy

To examine the influence of parent and family general and epilepsy‐related stress on longitudinal generic and epilepsy‐specific health‐related quality of life (HRQOL) for children with new‐onset epilepsy, while controlling for demographic characteristics, disease factors, and antiepileptic drug (AED) adherence.

Preliminary Feasibility, Acceptability, and Efficacy of an Innovative Adherence Intervention for Children With Newly Diagnosed Epilepsy

OBJECTIVE To report acceptability, feasibility, and preliminary efficacy from a randomized controlled trial of a family-tailored adherence intervention (AI) targeting nonadherence to antiepileptic drugs in pediatric new-onset epilepsy. METHOD 30 children with new-onset epilepsy (7.2 ± 3.1 years old, 47% male) and their caregivers participated. At baseline, participants were given adherence electronic monitors. After a 1-month run-in period, participants with good adherence (≥90%) were monitored. Participants with adherence <90% were randomized to the AI or Treatment-As-Usual (TAU) group. The AI group received four adherence promotion intervention sessions over >2 months. Follow-up adherence data were collected. RESULTS 8 families were randomized (AI, n = 4; TAU, n = 4). Families perceived AI to be feasible and acceptable. Preliminary results demonstrated that the AI group had improved adherence from baseline to post-test. CONCLUSIONS A family-tailored AI appears promising and needs to be tested with a larger pediatric epilepsy sample.

Early pediatric antiepileptic drug nonadherence is related to lower long-term seizure freedom

Objective: To examine the relationship between previously identified nonadherence trajectories during the first 6 months of antiepileptic drug (AED) therapy and long-term seizure-free rates (defined as ≥1 year of seizure freedom at the 4 years postdiagnosis milestone) in a cohort of children with newly diagnosed epilepsy. Methods: A prospective longitudinal observational study of AED adherence and seizure freedom in a consecutive cohort of 124 children (ages 2–12 years) with newly diagnosed epilepsy was conducted. The association between previously identified AED adherence trajectories (i.e., near-perfect adherence [e.g., average adherence = 96.8%] vs nonadherent) and seizure freedom for ≥1 year at the 4 years postdiagnosis milestone was determined. Results: Children who exhibited nonadherence to AED therapy in the first 6 months of treatment were 3.24 times more likely not to have achieved ≥1 year of seizure freedom at the 4 years postdiagnosis milestone compared to children in the near-perfect adherence group (χ2 = 5.13; p = 0.02). Specifically, at the 4 years postdiagnosis milestone, only 12% of children in the near-perfect adherence group were continuing to experience seizures compared to 31% of children in the nonadherent group. Conclusions: Children with epilepsy who achieved near-perfect adherence during the first 6 months of therapy experienced a higher rate of seizure freedom 4 years postdiagnosis compared with those children who demonstrated early nonadherence. This suggests that adherence intervention early in the course of treatment could play a role in improving long-term seizure freedom rates in children with epilepsy.