Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice.

The gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human epilepsy is unclear. We find that the clinical KD alters gut microbial function in children with refractory epilepsy. Colonizing mice with KD-associated microbes promotes seizure resistance relative to matched pre-treatment controls. Select metagenomic and metabolomic features, including those related to anaplerosis, fatty acid ß-oxidation, and amino acid metabolism, are seen with human KD therapy and preserved upon microbiome transfer to mice. Mice colonized with KD-associated gut microbes exhibit altered hippocampal transcriptomes, including pathways related to ATP synthesis, glutathione metabolism, and oxidative phosphorylation, and are linked to susceptibility genes identified in human epilepsy. Our findings reveal key microbial functions that are altered by KD therapies for pediatric epilepsy and linked to microbiome-induced alterations in brain gene expression and seizure protection in mice.

Health status, healthcare, and access in children with long-term medication use and difficulties with emotion, concentration, and behavior.

PROBLEM: Children with chronic conditions often have difficulties with emotions, concentration, and behaviors (ECB) and are not recognized and treated adequately. In this paper, long-term medication use (LTM) was adopted as a proxy for chronic illness due to the lack of consistent and standardized diagnostic criteria for chronic illnesses in children. METHODS: Children (8-12 years) were selected from the California Health Interview Survey (2017) based on: (1) households with children (<12 years), (2) parent/adult caregivers report about child's health indicating "yes" to, (3) "does your child require prescription medicine for a health condition that has lasted or is expected to last at least 12 months or more," and (4) "difficulties with ECB in past 6 months." FINDINGS: A total of 1600 children were included by the CHIS data set, and children whose parental report had met the selection criteria were children with LTM (n = 144; 7.4 ± 2.9 years), ECB (n = 233; 8.16 ± 2.14), and both LTM + ECB (n = 62; 8.61 ± 1.81). Children with LTM+ ECB were Caucasian (56.4%), Hispanic (19.3%), and males (64.5%). Children with both LTM + ECB had two to three (33.87%) or at least four (53.2%) physician visits, and/or receiving special therapy (45.1%). Children with LTM had prescription delays (n = 144; 5.6%) and were not able to get medical care due to lack of insurance (n = 144; 6.9%). The majority of the children with LTM (54.2%) and LTM + ECB (43.5%) had parental employment-based insurance. More children that have both LTM and ECB (48.4%) than children with LTM, No ECB (32.9%) were on Medi-Cal/Medicaid. CONCLUSION: Children with LTM need further evaluation for difficulties with ECB. Future studies are required to examine health status, healthcare use, and access for children with LTM and ECB.

Self-Management, Self-Efficacy, and Health-Related Quality of Life in Children With Chronic Illness and Medical Complexity.

INTRODUCTION: Children with chronic illnesses and medical complexity (CIMC) require frequent health-care use, thereby increasing medical care costs. We evaluated parent-child perceptions of self-management, self-efficacy, and health-related quality of life (HRQOL) in children with CIMC. METHOD: Parent-children pairs (n = 32) completed three measures before discharge from the hospital (Patient Activation Measure, Self-Efficacy Scale, and Acute Care-Pediatric Quality of Life for Children 8-12 and 13-17 years). RESULTS: Parents (56.3%) and children (40.6%) reported moderate levels of self-management. HRQOL was correlated with both self-management (r = .441, p = .12) and self-efficacy (r = .464, p = .008). At least 25% to 50% reported low PedsQL subscale scores (< 70), which indicate problems with physical, emotional, social, and mental domains. DISCUSSION: Our findings support the assessment of not only physical but also mental, emotional, and social needs in children with CIMC. We recommend development and testing strategies promoting self-management and self-efficacy to maximize HRQOL and improve health outcomes in children with CIMC.