Add-On Deep Brain Stimulation versus Continued Vagus Nerve Stimulation for Childhood Epilepsy (ADVANCE): A Partially Randomized Patient Preference Trial.

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024.

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study.

BACKGROUND: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. METHODS: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. FINDINGS: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). INTERPRETATION: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. FUNDING: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre.

An optimal search filter for retrieving systematic reviews and meta-analyses.

BACKGROUND: Health-evidence.ca is an online registry of systematic reviews evaluating the effectiveness of public health interventions. Extensive searching of bibliographic databases is required to keep the registry up to date. However, search filters have been developed to assist in searching the extensive amount of published literature indexed. Search filters can be designed to find literature related to a certain subject (i.e. content-specific filter) or particular study designs (i.e. methodological filter). The objective of this paper is to describe the development and validation of the health-evidence.ca Systematic Review search filter and to compare its performance to other available systematic review filters. METHODS: This analysis of search filters was conducted in MEDLINE, EMBASE, and CINAHL. The performance of thirty-one search filters in total was assessed. A validation data set of 219 articles indexed between January 2004 and December 2005 was used to evaluate performance on sensitivity, specificity, precision and the number needed to read for each filter. RESULTS: Nineteen of 31 search filters were effective in retrieving a high level of relevant articles (sensitivity scores greater than 85%). The majority achieved a high degree of sensitivity at the expense of precision and yielded large result sets. The main advantage of the health-evidence.ca Systematic Review search filter in comparison to the other filters was that it maintained the same level of sensitivity while reducing the number of articles that needed to be screened. CONCLUSIONS: The health-evidence.ca Systematic Review search filter is a useful tool for identifying published systematic reviews, with further screening to identify those evaluating the effectiveness of public health interventions. The filter that narrows the focus saves considerable time and resources during updates of this online resource, without sacrificing sensitivity.

Family Members' Perceptions of Their Psychological Responses One Year Following Pediatric Intensive Care Unit (PICU) Hospitalization: Qualitative Findings From the Caring Intensively Study.

Introduction: PICU hospitalization can have a profound impact on child survivors and their families. There is limited research on children's long-term recovery within the context of the family following critical illness. This study aimed to explore children's and parents' perceptions of long-term psychological and behavioral responses within the context of the family one year following PICU hospitalization. Materials and Methods: Caring Intensively is a mixed methods multi-site prospective cohort study that aims to examine children's psychological and behavioral responses over a 3-year period following PICU hospitalization. In this study, part of the qualitative arm of Caring Intensively, an interpretive descriptive design was used to explore children's recovery one year post-discharge. Purposive sampling was used to select 17 families, including 16 mothers, 6 fathers, and 9 children. Semi-structured, audio-recorded interviews were conducted. Data were analyzed iteratively using the constant comparison method. Results: Families described efforts to readapt to routine life and find a new normal following PICU hospitalization. Finding a New Normal consisted of four major themes: (1) Processing PICU Reminders and Memories, (2) Changing Perceptions of Health and Illness, (3) We Are Not the Same, and (4) Altered Relationships. Participants described significant emotional and behavioral changes during the year following discharge. The psychological impact of individual family members' experiences led to changes in their sense of self, which affected family dynamics. PICU memories and reminders impacted participants' perceptions of childhood health and illness and resulted in increased vigilance. Parents and siblings demonstrated increased concern for the child survivor's health, and the experience of long absences and new or altered caregiving roles resulted in changes in relationships and family dynamics. Conclusion: PICU hospitalization impacted the psychological well-being of all family members as they sought to re-establish a sense of normalcy one year following discharge. Parent and child experiences and responses were closely interconnected. Findings highlight the importance of increased follow-up care aimed at supporting the family's psychological recovery.

A Sleep Hygiene and Relaxation Intervention for Children With Acute Lymphoblastic Leukemia: A Pilot Randomized Controlled Trial.

BACKGROUND: Sleep disturbance and fatigue are common and distressing pediatric cancer-related outcomes. Sleep hygiene education and relaxation techniques are recommended to improve sleep in healthy children and adult cancer survivors. No studies have tested these interventions to improve sleep and fatigue for children with acute lymphoblastic leukemia (ALL) in the home setting. OBJECTIVES: The aim of this study is to establish the feasibility and acceptability of a sleep hygiene and relaxation intervention to improve sleep and fatigue for children receiving maintenance chemotherapy for ALL. The child's fatigue and sleep data were collected to inform sample size calculations for a future trial. METHODS: In this pilot randomized controlled trial, 20 children were allocated randomly to the sleep intervention or control group. The sleep intervention group received a 60-minute educational session to discuss sleep and fatigue in children with cancer and strategies to improve sleep, including use of 2 storybooks to teach deep breathing and progressive muscle relaxation. Objective sleep data were collected using actigraphy and fatigue was measured using the Childhood Cancer Fatigue Scale. RESULTS: The intervention was acceptable to families, and feasibility of the intervention and data collection was clearly established. Although not statistically significant, increases in mean nighttime sleep and decreases in mean wake time after sleep onset in the sleep intervention group represented clinically important improvements. CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a sleep hygiene and relaxation intervention for children undergoing maintenance chemotherapy for ALL. IMPLICATIONS FOR PRACTICE: Given the clinically important improvements in sleep observed, replication in a larger, adequately powered randomized controlled trial is merited.