Epilepsy-specific patient-reported outcome measures of children's health-related quality of life: A systematic review of measurement properties.

This is the final version. Available from the publisher via the DOI in this record.OBJECTIVE: To identify and appraise published evidence of the measurement properties for epilepsy-specific patient-reported outcome measures (PROMs) of children's health-related quality of life (HRQoL). METHODS: We searched multiple databases for studies evaluating the measurement properties of English-language epilepsy-specific PROMs of children's HRQoL. We assessed the methodological quality using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidance. We extracted data about the content validity, construct validity, internal consistency, test-retest reliability, proxy reliability, responsiveness, and precision, and assessed the measurement properties with reference to standardized criteria. RESULTS: We identified 27 papers that evaluated 11 PROMs. Methodological quality was variable. Construct validity, test-retest reliability, and internal consistency were more commonly assessed. Quality of Life in Childhood Epilepsy (QoLCE) questionnaires are parent-reported and evaluated more than other PROMs; QoLCE-55 has good and replicated evidence for structural and construct validity and internal consistency. Health-Related Quality of Life Measure for Children with Epilepsy (CHEQoL) has both child and parent-reported versions and good evidence of content, structural, and construct validity. SIGNIFICANCE: This review identified two leading candidate epilepsy-specific PROMs for measuring health-related quality of life in children. Establishing evidence of the responsiveness of PROMs is a priority to help the interpretation of meaningful change scores.National Institute for Health Research (NIHR

Mapping epilepsy-specific patient-reported outcome measures for children to a proposed core outcome set for childhood epilepsy

This is the final version. Available on open access from Elsevier via the DOI in this recordObjective: The objectives of the study were to (1) map questions in epilepsy-specific patient-reported outcome measures (PROMs) of children's health-related quality of life (HRQoL) to a proposed core outcome set (COS) for childhood epilepsy research and (2) gain insight into the acceptability of two leading candidate PROMs. Method: We identified 11 epilepsy-specific PROMs of children's HRQoL (17 questionnaire versions) in a previous systematic review. Each item from the PROMs was mapped to 38 discrete outcomes across 10 domains of the COS: seizures, sleep, social functioning, mental health, cognition, physical functioning, behavior, adverse events, family life, and global quality of life. We consulted with three children with epilepsy and six parents of children with epilepsy in Patient Public Involvement and Engagement (PPIE) work to gain an understanding of the acceptability of the two leading PROMs from our review of measurement properties: Quality of Life in Childhood Epilepsy (QOLCE-55) and Health-Related Quality of Life Measure for Children with Epilepsy (CHEQOL). Results: Social Functioning is covered by all PROMs except DISABKIDS and G-QOLCE and Mental Health is covered by all PROMs except G-QOLCE and Hague Restrictions in Childhood Epilepsy Scale (HARCES). Only two PROMs (Epilepsy and Learning Disability Quality of Life (ELDQOL) and Glasgow Epilepsy Outcome Scale (GEOS-YP)) have items that cover the Seizure domain. The QOLCE-55 includes items that cover the domains of Physical Functioning, Social Functioning, Behavior, Mental Health, and Cognition. The CHEQOL parent and child versions cover the same domains as QOLCE-55 except for Physical Functioning and Behavior, and the child version has one item that covers the discrete outcome of Overall Quality of Life and one item that covers the discrete outcome of Relationship with parents and siblings. The QOLCE-55 parent version was acceptable to the parents we consulted with, and CHEQOL parent and child versions were described as acceptable to our child and parent advisory panel members. Significance: Mapping items from existing epilepsy-specific PROMs for children is an important step in operationalizing our COS for childhood epilepsy research, alongside evaluation of their measurement properties. Two leading PROMS, QOLCE-55 and CHEQOL, cover a wide range of domains from our COS and would likely be used in conjunction with assessment tools selected for specific study objectives. The PPIE work provided practical insights into the administration and acceptability of candidate PROMs in appropriate context. We promote our COS as a framework for selecting outcomes and PROMs for future childhood epilepsy evaluative research.National Institute for Health Research (NIHR)Canadian Institutes of Health ResearchWaterloo FoundationCharles Sykes Epilepsy Research Trus

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers

This is the final version of the article. Available from Springer Nature via the DOI in this record.The dataset generated during the current study are available from the corresponding author on reasonable request.Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.This research was funded by a PhD Studentship from the Medical Research Council (MRC) to the C.H. and an MRC DPFS award (MR/K015524/1) to HVC and CJAM.TPF is funded by a Senior Academic Fellowship from the Society for the Study of Addiction

Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E: A protocol for a randomised controlled trial comparing an online behavioural sleep intervention with standard care in children with Rolandic epilepsy

This is the final version. Available from BMJ Publishing Group via the DOI in this record. INTRODUCTION: Sleep and epilepsy have an established bidirectional relationship yet only one randomised controlled clinical trial has assessed the effectiveness of behavioural sleep interventions for children with epilepsy. The intervention was successful, but was delivered via face-to-face educational sessions with parents, which are costly and non-scalable to population level. The Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E trial addresses this problem by comparing clinical and cost-effectiveness in children with Rolandic epilepsy between standard care (SC) and SC augmented with a novel, tailored parent-led CASTLE Online Sleep Intervention (COSI) that incorporates evidence-based behavioural components. METHODS AND ANALYSES: CASTLE Sleep-E is a UK-based, multicentre, open-label, active concurrent control, randomised, parallel-group, pragmatic superiority trial. A total of 110 children with Rolandic epilepsy will be recruited in outpatient clinics and allocated 1:1 to SC or SC augmented with COSI (SC+COSI). Primary clinical outcome is parent-reported sleep problem score (Children's Sleep Habits Questionnaire). Primary health economic outcome is the incremental cost-effectiveness ratio (National Health Service and Personal Social Services perspective, Child Health Utility 9D Instrument). Parents and children (≥7 years) can opt into qualitative interviews and activities to share their experiences and perceptions of trial participation and managing sleep with Rolandic epilepsy. ETHICS AND DISSEMINATION: The CASTLE Sleep-E protocol was approved by the Health Research Authority East Midlands (HRA)-Nottingham 1 Research Ethics Committee (reference: 21/EM/0205). Trial results will be disseminated to scientific audiences, families, professional groups, managers, commissioners and policymakers. Pseudo-anonymised individual patient data will be made available after dissemination on reasonable request. TRIAL REGISTRATION NUMBER: ISRCTN13202325.National Institute for Health and Care Research (NIHR)National Health and Medical Research Council (NHMRC, Australia)Victorian Government’s Operational Infrastructure Support Progra

Risk and protective factors for self-harm and suicide in children and adolescents: a systematic review and meta-analysis protocol.

Introduction Self-harm and suicide are major public health concerns among children and adolescents. Many risk and protective factors for suicide and self-harm have been identified and reported in the literature. However, the capacity of these identified risk and protective factors to guide assessment and management is limited due to their great number. This protocol describes an ongoing systematic review and meta-analysis which aims to examine longitudinal studies of risk factors for self-harm and suicide in children and adolescents, to provide a comparison of the strengths of association of the various risk factors for self-harm and suicide and to shed light on those that require further investigation. Methods and analysis We perform a systematic search of the literature using the databases EMBASE, PsycINFO, Medline, CINAHL and HMIC from inception up to 28 October 2020, and the search will be updated before the systematic review publication. Additionally, we will contact experts in the field, including principal investigators whose peer-reviewed publications are included in our systematic review as well as investigators from our extensive research network, and we will search the reference lists of relevant reviews to retrieve any articles that were not identified in our search. We will extract relevant data and present a narrative synthesis and combine the results in meta-analyses where there are sufficient data. We will assess the risk of bias for each study using the Newcastle–Ottawa Scale and present a summary of the quantity and the quality of the evidence for each risk or protective factor. Ethics and dissemination Ethical approval will not be sought as this is a systematic review of the literature. Results will be published in mental health journals and presented at conferences focused on suicide prevention

No selection for change in polyandry under experimental evolution

What drives mating system variation is a major question in evolutionary biology. Female multiple mating (polyandry) has diverse evolutionary consequences, and there are many potential benefits and costs of polyandry. However, our understanding of its evolution is biased towards studies enforcing monandry in polyandrous species. What drives and maintains variation in polyandry between individuals, genotypes, populations and species remains poorly understood. Genetic variation in polyandry may be actively maintained by selection, or arise by chance if polyandry is selectively neutral. In Drosophila pseudoobscura, there is genetic variation in polyandry between and within populations. We used isofemale lines to found replicate populations with high or low initial levels of polyandry and tracked polyandry under experimental evolution over seven generations. Polyandry remained relatively stable, reflecting the starting frequencies of the experimental populations. There were no clear fitness differences between high versus low polyandry genotypes, and there was no signature of balancing selection. We confirmed these patterns in direct comparisons between evolved and ancestral females and found no consequences of polyandry for female fecundity. The absence of differential selection even when initiating populations with major differences in polyandry casts some doubt on the importance of polyandry for female fitness

Trait impulsivity in Juvenile Myoclonic Epilepsy

Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs)

The impact of parent treatment preference and other factors on recruitment: lessons learned from a paediatric epilepsy randomised controlled trial

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The CASTLE trial was terminated after the pilot. The datasets used and/or analysed during the CASTLE pilot as well as select trial materials are available from the corresponding author (DP) on reasonable request (see also pages 53-54 of the attached protocol). The information from the consultation with the health professionals is not available as this is not research data.Background In paediatric epilepsy, the evidence of effectiveness of antiseizure treatment is inconclusive for some types of epilepsy. As with other paediatric clinical trials, researchers undertaking paediatric epilepsy clinical trials face a range of challenges that may compromise external validity Main body In this paper, we critically reflect upon the factors which impacted recruitment to the pilot phase of a phase IV unblinded, randomised controlled 3×2 factorial trial examining the effectiveness of two antiseizure medications (ASMs) and a sleep behaviour intervention in children with Rolandic epilepsy. We consider the processes established to support recruitment, public and patient involvement and engagement (PPIE), site induction, our oversight of recruitment targets and figures, and the actions we took to help us understand why we failed to recruit sufficient children to continue to the substantive trial phase. The key lessons learned were about parent preference, children’s involvement and collaboration in decision-making, potential and alternative trial designs, and elicitation of stated preferences pre-trial design. Despite pre-funding PPIE during the trial design phase, we failed to anticipate the scale of parental treatment preference for or against antiseizure medication (ASMs) and consequent unwillingness to be randomised. Future studies should ensure more detailed and in-depth consultation to ascertain parent and/or patient preferences. More intense engagement with parents and children exploring their ideas about treatment preferences could, perhaps, have helped predict some recruitment issues. Infrequent seizures or screening children close to natural remission were possible explanations for non-consent. It is possible some clinicians were unintentionally unable to convey clinical equipoise influencing parental decision against participation. We wanted children to be involved in decisions about trial participation. However, despite having tailored written and video information to explain the trial to children we do not know whether these materials were viewed in each consent conversation or how much input children had towards parents’ decisions to participate. Novel methods such as parent/patient preference trials and/or discrete choice experiments may be the way forward. Conclusion The importance of diligent consultation, the consideration of novel methods such as parent/patient preference trials and/or discrete choice experiments in studies examining the effectiveness of ASMs versus no-ASMs cannot be overemphasised even in the presence of widespread clinician equipoise.National Institute for Health Research (NIHR