Interactive video games to reduce paediatric procedural pain and anxiety: a systematic review and meta-analysis

Background: Procedural pain and anxiety in children can be poorly controlled, leading to significant short- and long-term sequelae, such as longer procedure times or future healthcare avoidance. Caregiver anxiety can exacerbate these effects. We aimed to evaluate the effect of interactive video game interventions on children's procedural pain and anxiety, including the effect of different types of video games on those outcomes. Methods: We conducted a systematic review and meta-analysis of the effectiveness of interactive video games compared with standard care in children (0–18 yr) undergoing painful procedures. We searched the databases MEDLINE, Embase, and PsycINFO. We conducted random-effects meta-analysis using ‘R’ of children's procedural pain and anxiety and caregivers' anxiety. Results: Of 2185 studies screened, 36 were eligible (n=3406 patients). Studies commonly involved venous access (33%) or day surgery (31%). Thirty-four studies were eligible for meta-analyses. Interactive video games appear to reduce children's procedural pain (standardised mean difference [SMD]=–0.43; 95% confidence interval [CI]: –0.67 to –0.20), anxiety (SMD=0.61; 95% CI: –0.88 to –0.34), and caregivers' procedural anxiety (SMD=–0.31; 95% CI: –0.58 to –0.04). We observed no difference between preparatory and distracting games, or between virtual reality and non-virtual reality games. We also observed no difference between interactive video games compared with standard care for most medical outcomes (e.g. procedure length), except a reduced need for restraint. Studies reported minimal adverse effects and typically had high intervention acceptability and satisfaction. Conclusions: Our findings support introducing easily available video games, such as distraction-based conventional video games, into routine practice to minimise paediatric procedural pain and child/caregiver anxiety

Acceptability and feasibility of an online information linker service for caregivers who have a child with genetic epilepsy: A mixed-method pilot study protocol

Introduction Developmental and epileptic encephalopathies (DEEs) are rare epilepsy conditions that collectively impact 1 in 2000 children. They are highly genetically heterogeneous, resulting in significant barriers to accurate and adequate information for caregivers. This can lead to increased distress and dissatisfaction with the healthcare system. To address this gap, we developed € GenE Compass' to provide caregivers with the highest-quality possible, understandable and relevant information in response to specific questions about their child's DEE. Using a mixed-method design, we will now pilot GenE Compass to evaluate the acceptability to caregivers and clinicians, feasibility and impact to caregivers. Methods and analysis We will recruit 88 caregivers (estimated final sample of 50 at follow-up) who have a child under 18 years of age with a suspected or confirmed DEE diagnosis. Following consent and a baseline questionnaire (questionnaire 1 (Q1)), participants will be able to submit questions to GenE Compass over a 3-month period. After 3 months, participants will complete a follow-up questionnaire (Q2) and an optional telephone interview to answer the research questions. Primary outcomes are acceptability of GenE Compass and feasibility of delivering the intervention (eg, cost of the intervention, number of questions submitted and time taken to respond to questions). Secondary outcomes include the impact of GenE Compass on caregivers' quality of life, information searching behaviours, perceptions of their child's illness and activation. Ethics and discussion The study protocol (V.2, dated 16 September 2021) has been approved by the Sydney Children's Hospitals Network Human Research Ethics Committee (ETH11277). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be disseminated to all participants. Trial registration number ACTRN12621001544864

Transcriptional targets of the schizophrenia risk gene MIR137

Genome-wide association studies (GWAS) have strongly implicated MIR137 (the gene encoding the microRNA miR-137) in schizophrenia. A parsimonious hypothesis is that a pathway regulated by miR-137 is important in the etiology of schizophrenia. Full evaluation of this hypothesis requires more definitive knowledge about biological targets of miR-137, which is currently lacking. Our goals were to expand knowledge of the biology of miR-137 by identifying its empirical targets, and to test whether the resulting lists of direct and indirect targets were enriched for genes and pathways involved in risk for schizophrenia. We overexpressed miR-137 in a human neural stem cell line and analyzed gene expression changes at 24 and 48 h using RNA sequencing. Following miR-137 overexpression, 202 and 428 genes were differentially expressed after 24 and 48 h. Genes differentially expressed at 24 h were enriched for transcription factors and cell cycle genes, and differential expression at 48 h affected a wider variety of pathways. Pathways implicated in schizophrenia were upregulated in the 48 h findings (major histocompatibility complex, synapses, FMRP interacting RNAs and calcium channels). Critically, differentially expressed genes at 48 h were enriched for smaller association P-values in the largest published schizophrenia GWAS. This work provides empirical support for a role of miR-137 in the etiology of schizophrenia

Providing psychological support to parents of childhood cancer survivors: ‘cascade’ intervention trial results and lessons for the future

We conducted a three‐armed trial to assess Cascade, a four‐module group videoconferencing cognitive behavior therapy (CBT) intervention for parents of childhood cancer survivors currently aged <18 years. We allocated parents to Cascade, an attention control (peer‐ support group), or a waitlist. The primary outcome was parents’ health‐related quality of life (PedsQL‐Family Impact/EQ‐5D‐5L) six months post‐intervention. Parents also reported their anxiety/depression, parenting self‐agency, fear of recurrence, health service and psychotropic medication use, engagement in productive activities, confidence to use, and actual use of, CBT skills, and their child’s quality of life. Seventy‐six parents opted in; 56 commenced the trial. Cascade achieved good parent engagement and most Cascade parents were satisfied and reported benefits. Some parents expressed concerns about the time burden and the group format. Most outcomes did not differ across trial arms. Cascade parents felt more confident to use more CBT skills than peer-support and waitlisted parents, but this did not lead to more use of CBT. Cascade parents reported lower psychosocial health scores for their child than waitlisted parents. Cascade parents’ health service use, psychotropic medication use, and days engaged in productive activities did not improve, despite some improvements in waitlisted parents. Our trial was difficult to implement, but participants were largely satisfied. Cascade did not improve most outcomes, possibly because many parents were functioning well pre‐enrolment. We used these findings to improve Cascade and will trial the new version in future

Genetic Analysis of Hematological Parameters in Incipient Lines of the Collaborative Cross

Hematological parameters, including red and white blood cell counts and hemoglobin concentration, are widely used clinical indicators of health and disease. These traits are tightly regulated in healthy individuals and are under genetic control. Mutations in key genes that affect hematological parameters have important phenotypic consequences, including multiple variants that affect susceptibility to malarial disease. However, most variation in hematological traits is continuous and is presumably influenced by multiple loci and variants with small phenotypic effects. We used a newly developed mouse resource population, the Collaborative Cross (CC), to identify genetic determinants of hematological parameters. We surveyed the eight founder strains of the CC and performed a mapping study using 131 incipient lines of the CC. Genome scans identified quantitative trait loci for several hematological parameters, including mean red cell volume (Chr 7 and Chr 14), white blood cell count (Chr 18), percent neutrophils/lymphocytes (Chr 11), and monocyte number (Chr 1). We used evolutionary principles and unique bioinformatics resources to reduce the size of candidate intervals and to view functional variation in the context of phylogeny. Many quantitative trait loci regions could be narrowed sufficiently to identify a small number of promising candidate genes. This approach not only expands our knowledge about hematological traits but also demonstrates the unique ability of the CC to elucidate the genetic architecture of complex traits

Identification of an ATP/P2X7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR

Genetic Regulation of Zfp30, CXCL1, and Neutrophilic Inflammation in Murine Lung

Allergic asthma is a complex disease characterized in part by granulocytic inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are also present, particularly in cases of severe asthma. We sought to identify the genetic determinants of neutrophilic inflammation in a mouse model of house dust mite (HDM)-induced asthma. We applied an HDM model of allergic asthma to the eight founder strains of the Collaborative Cross (CC) and 151 incipient lines of the CC (preCC). Lung lavage fluid was analyzed for PMN count and the concentration of CXCL1, a hallmark PMN chemokine. PMN and CXCL1 were strongly correlated in preCC mice. We used quantitative trait locus (QTL) mapping to identify three variants affecting PMN, one of which colocalized with a QTL for CXCL1 on chromosome (Chr) 7. We used lung eQTL data to implicate a variant in the gene Zfp30 in the CXCL1/PMN response. This genetic variant regulates both CXCL1 and PMN by altering Zfp30 expression, and we model the relationships between the QTL and these three endophenotypes. We show that Zfp30 is expressed in airway epithelia in the normal mouse lung and that altering Zfp30 expression in vitro affects CXCL1 responses to an immune stimulus. Our results provide strong evidence that Zfp30 is a novel regulator of neutrophilic airway inflammation