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Susan Young,1,2 Michael Absoud,3 Zainab Al-Attar,4,5 Cornelius Ani,6,7 William Colley,8 Samuele Cortese,9– 13 Jo Crame,14 Gisli Gudjonsson,2,15 Peter Hill,16 Jack Hollingdale,17 Raja AS Mukherjee,18,19 Susan Ozer,20 Gavin Partridge,21 Jade Smith,22 Emma Louise Woodhouse,17,23 Alexandra Lewis24 1Independent Practice, Psychology Services Limited, London, UK; 2Department of Psychology, Reykjavik University, Reykjavik, Iceland; 3Department of Children’s Neurosciences, Evelina London Children’s Hospital, Guys and St Thomas’ NHS Foundation Trust, London, UK; 4Independent Practice, Psychiatry UK, London, UK; 5Department of Psychiatry, University of Oxford, Oxford, UK; 6Division of Psychiatry, Imperial College London, London, UK; 7Neurodevelopmental Team, Children and Young People’s Service, Surrey and Borders Partnership NHS Foundation Trust, Leatherhead, UK; 8Independent Practice, CLC Consultancy, Dunkeld, UK; 9Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; 10Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; 11Child and Adolescent Mental Health Service, Solent NHS Trust, Southampton, UK; 12Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA; 13DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari “Aldo Moro”, Bari, Italy; 14Service-User Representative, Surrey, UK; 15Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 16Independent Practice, London, WC1N 3HB, UK; 17Independent Practice, Compass Psychology Services Ltd, London, UK; 18ASD and ADHD Service, Horizon, Epsom, UK; 19University of Surrey Medical School, Guildford, UK; 20Child Development Centre, East and North Hertfordshire NHS Trust, Stevenage, UK; 21Partridge ADHD Clinic, Oxford, UK; 22Children and Young People’s Neurodevelopmental Service, Humber NHS Foundation Trust, Hull and East Riding, UK; 23Department of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 24Fulbourn Hospital, Cambridgeshire and Peterborough Foundation NHS Trust, Cambridge, UKCorrespondence: Susan Young, Email SuzyYoung@aol.comAbstract: Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population. The ADHD Assessment Quality Assurance Standard for Children and Teenagers [CAAQAS] aims to address this by proposing a quality framework for ADHD assessments in this population. CAAQAS is intended to complement formal training, provide support to clinicians, inform commissioners, and empower children, teenagers, and caregivers on what to expect from an assessment and assessment report. Our goal is to promote evidence-based high-quality assessments, improve diagnostic accuracy, and reduce the risks of overdiagnosis, misdiagnosis, and underdiagnosis. Seven key topics were identified by authors which guided the development of this expert consensus statement. It was agreed that a high-quality diagnostic assessment of ADHD in this population commences with advance preparation to facilitate engagement of the child or teenager and caregivers. The consensus agreed that the minimum/essential standards for assessing and diagnosing ADHD adopt a systematic approach from pre-assessment through assessment to post-diagnostic stage, enabling ADHD to be disentangled from differential diagnoses. The process applies multi-source information to inform an assessment of development history and early risk factors, history of physical, mental health and other neurodevelopmental conditions, family, educational, and social histories. Assessment of core ADHD symptoms should include specific developmentally appropriate examples of associated difficulties and impairments. Neuropsychiatric and physical comorbidities should be assessed and identified. Recommendations for report writing are intended to facilitate effective communication between ADHD specialists and other services, and we highlight the importance of linking the diagnosis to an appropriate post-diagnostic discussion. Further, we discuss core competencies required to conduct a diagnostic assessment of ADHD in children and teenagers.Keywords: attention deficit hyperactivity disorder, practice guidelines, diagnosis, children, teenagers, assessment

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Introduction: Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. Methods and analysis: 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is ‘good recovery’ (score of 2 or lower on the Glasgow Outcome Score Extended—paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4–6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. Ethics and dissemination: This trial has been approved by the UK National Research Ethics committee (South Central—Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. [ABSTRACT FROM AUTHOR]

The new McDonald 2010 criteria have been recommended in paediatric multiple sclerosis (PMS). We aimed to assess the utility of McDonald 2010 criteria in comparison with 2007 International Paediatric Multiple Sclerosis Study Group (IPMSSG)-recommended criteria for PMS diagnosis. Retrospective analysis of 38 PMS cases from three UK demyelination clinics was conducted. Dissemination in space (DIS) and time (DIT) for both McDonald and IPMSSG criteria were noted on initial and follow-up magnetic resonance imaging (MRI). At first MRI scan, IPMSSG DIS criteria were fulfilled in 68% of scans and McDonald DIS criteria in 84%. In total, 11/18 children given gadolinium contrast fulfilled both McDonald DIS and DIT criteria on initial scan. The 2010 McDonald criteria appear more sensitive than IPMSSG and may allow PMS diagnosis at first presentation of CIS in at least a half of cases. [ABSTRACT FROM AUTHOR]

There is a paucity of literature on the epidemiology of severe acute disseminated encephalomyelitis (ADEM). We describe a Paediatric Intensive Care Unit (PICU) population-based study to determine the epidemiology and clinical characteristics of children with ADEM requiring PICU admission or resulting in death. Anonymized data from the Paediatric Intensive Care Audit Network (PICANet) were obtained for all children under 16 years with a diagnosis of ADEM admitted to 25 PICUs in England and Wales (2004–2008). The Office for National Statistics (ONS) mortality database was also searched. In total, 27 PICANet cases (13 females:14 males; median age 4.8 years) were ascertained and all were alive on discharge. In addition, three cases were identified from the ONS mortality database. Of the 27 PICANet cases, clinical features included; seizures (n = 5); upper airway respiratory obstruction/stridor (n = 2); unspecified encephalopathy (n = 27); and polyfocal neurological deficits (n = 6). The median duration of ventilation was 3 days. Inotropic support was required in 4/27 patients, and one patient had invasive intracranial pressure monitoring. None received plasmapheresis. We conclude that the incidence of childhood ADEM admitted to the PICU in England and Wales is approximated at 0.5 per million children/year, thus representing approximately one quarter of children admitted with ADEM (denominator: 2009 Canadian surveillance data). [ABSTRACT FROM AUTHOR]

Background: Children with an intellectual disability (ID) are 3-4 times more likely to present with behaviors that challenge and mental health problems than typically developing children. Parenting and the quality of parent-child relationships are risk factors for these families. The COVID-19 pandemic further exacerbated difficulties, leading to an increase in child mental health problems and behaviors that challenge, a deterioration in parental mental health, and further strain on family relationships. Remote family interventions could be an effective solution for both families and specialist mental health services. Video interaction guidance (VIG) has shown promise for improving child mental health. However, it is unclear whether it is widely acceptable to families and feasible to implement across specialist child mental health services., Objective: This randomized controlled trial aims to evaluate the feasibility of delivering VIG as a remote intervention for parents of children aged 6-12 years with ID who have been referred to specialist mental health services., Methods: The study will be undertaken across 5-7 National Health Service specialist mental health services in England, involving 50 participants randomly allocated on a 1:1 basis to either the intervention group (receiving remote VIG) or the treatment-as-usual (TAU) group. The intervention group will engage in 3-5 cycles of VIG delivered remotely over 12 weeks. The primary feasibility outcomes include the recruitment rate, retention at 6-month follow-up, and VIG cycle completion rate. The secondary outcomes will assess the acceptability of VIG and the feasibility of remote implementation, including fidelity to the intervention protocol. Data will be gathered through online surveys and telephone interviews at baseline, 3 months, and 6 months. Feasibility outcomes will be summarized using descriptive statistics, while thematic analysis will be applied to qualitative data from semistructured interviews with participants, VIG practitioners, and service managers. An embedded process evaluation will explore barriers and facilitators to engagement with VIG, and a parallel health economics evaluation will assess the feasibility of capturing service use data and intervention costs., Results: The trial was open to recruitment between December 2022 and March 2024. The first results should be available in 2025., Conclusions: The study is the first randomized evaluation of VIG as offered to parents of children with ID who have been referred to specialist mental health settings. The outcomes from this feasibility trial will inform the decision to proceed with a definitive trial, using a traffic light system to evaluate recruitment, retention, and VIG completion rates alongside qualitative insights and economic evaluations., Trial Registration: ISRCTN Registry ISRCTN13171328; http://www.isrctn.com/ISRCTN13171328., International Registered Report Identifier (irrid): DERR1-10.2196/54619., (©Charmaine Kohn, Lauren Turner, Zhixing Yang, Michael Absoud, Angela Casbard, Manuel Gomes, Gemma Grant, Angela Hassiotis, Eilis Kennedy, Sophie Levitt, Rachel McNamara, Elizabeth Randell, Vasiliki Totsika. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.12.2024.)

It is unknown if cognition is impaired before clinical onset of paediatric acquired demyelinating syndromes. We conducted a matched cohort study using prospectively collected educational data in multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) patients (n = 60) and controls (pooled n = 449,553). Academic performance at ages 10-11 was impaired in MOGAD (-1.27 adjusted z-score [95% CI: -1.81 to -0.73], P < 0.001) and preclinical MS (-0.40 [-0.80 to -0.0003], P = 0.0498). Moderate/high-efficacy MS treatment was associated with better final academic performance (0.92 [0.28-1.57], P = 0.005). After clinical onset MS patients missed 8.7% of school (controls 2.9%, P < 0.001) and MOGAD patients 11.9% (controls 2.0%, P < 0.001)., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Aims and Method: This survey of 66 specialist mental health services aimed to provide an up-to-date description of pathways of care and interventions available to children with an intellectual disability referred for behaviours that challenge or with suspected mental health problems., Results: Overall, 24% of services made contact with a family at referral stage, whereas 29% contacted families at least once during the waiting list phase. Only two in ten services offered any therapeutic input during the referral or waiting list stages. During the active caseload phase, services offered mostly psychoeducation (52-59%), followed by applied behaviour analytic approaches for behaviours that challenge (52%) and cognitive-behavioural therapy (41%). Thirty-six per cent of services had not offered any packaged or named intervention in the past 12 months., Clinical Implications: With increasing waiting times for specialist mental health support, services need to consider increasing the amount of contact and therapeutic input on offer throughout all stages of a child's journey with the service.

Objectives: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS)., Methods: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively., Results: A total of 269 children were recruited and followed up for a median of 7.2 years. Median age at onset was 9y (IQR 9.5-14.5, 126 females). At last follow-up, 46 (18 %) had MS, 4 AQP4-Ab NMOSD and 206 (80 %) had other ADS, of which 27 (13 %) relapsed. Relapsing MOGAD was the diagnosis in 12/27, 6 were seronegative and 9 did not have antibodies tested. Frequency of relapse differed according to first presentation in non-MS ADS, being least likely in transverse myelitis (p = 0.025). In the non-MS group, MOG-Ab was predictive of relapse (HR = 8.42; p < 0.001) occurring 8 times as often decreasing over time. Long-term difficulties did not differ between children with monophasic vs relapsing diseases., Conclusion: The risk of relapse in non-MS ADS depends on initial diagnosis, and MOG-Ab positivity. Long-term difficulties are observed regardless of relapses and are determined by presenting phenotype., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England., Study Design: 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed., Results: We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-£1,057.88; 95% CI -£3,218.6 to -£46.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups., Conclusion: This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Royston et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

[Background and aim] Early onset epilepsy is a neurological condition with significant developmental consequences, and presents affected children and families with challenges which pervade many aspects of family life. Whilst the concerns of parents and the impact on quality of life is well documented in qualitative research, little emphasis has been placed on the context of 'early onset', and the implications of these concerns for research priority setting. We aimed to explore parental perspectives regarding concerns and the impact of early onset epilepsy on the child and family, and to identify priorities for future paediatric epilepsy research. [Methods] The Brain development in Early Epilepsy: Parent Priorities (BEE-PP) project employed a mixed methods approach to collect information on parents' experience of having a child diagnosed with early onset epilepsy before 36 months old and aged up to 16 years old. Parents completed an online survey (n = 15) followed by a focus group (n = 5) to explore their main concerns regarding early onset epilepsy, the impact on family life and research priorities. [Results] A thematic analysis of the focus group data generated eight themes related to concerns of parents, the impact on the family and research priorities. The three main concerns identified were the expected trajectory of their child's development, a lack of seizure control following diagnosis and adverse behavioural side effects of medication. Within family life, early onset epilepsy had an impact on sibling autonomy and psychosocial adaptation, poorer parental wellbeing and restricted social and personal activities. The need for clearer information regarding their child's developmental trajectory, and managing the side effects of medication and their interactions with behaviour over time were topics of priority for future epilepsy research. [Interpretation] The impact of early onset epilepsy on the family is pervasive and requires the provision of appropriate healthcare service-led support for families to improve quality of life and children's adjustment to epilepsy. Regular monitoring of the concerns of parents and the impact of the diagnosis would be beneficial for addressing epilepsy-related and psychosocial needs of the wider family throughout their child's development. Implications for future research priority setting with regards to improved clinician-to-parent information sharing and managing the behavioural side effects of medication are discussed., Competing Interests: Declaration of competing interest Dr. Charman has acted as a paid consultant to F. Hoffmann-La Roche Ltd. and Servier; and has received royalties from Sage Publications and Guilford Publications., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles., Methods and Analysis: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms., Ethics and Dissemination: To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET&#95;62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters)., Competing Interests: Competing interests: In the past 3 years, TC has served as a paid consultant to F. Hoffmann-La Roche and Servier and has received royalties from Sage Publications and Guilford Publications. DGMM has received funding for a PhD studentship from Compass, and for consulting from Jaguar Therapeutics and Hoffman Le Roche. GM receives funding for an investigator-initiated study from Compass Pathways; no financial or other conflict of interest with the present study. SB discloses that he has in the last 3 years acted as an author, consultant, or lecturer for Medice, Roche and Linus Biotechnology. SB receives royalties for textbooks and diagnostic tools from Hogrefe, UTB, Ernst Reinhardt, Kohlhammer, and Liber, and is a partner at NeuroSupportSolutions International AB. CC is a full-time employee of Genentech and owns stocks or RSUs in Roche Holdings. MA is the UK chief investigator for a trial sponsored by Roche (a phase II, randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety, efficacy and pharmacodynamics of 52 weeks of treatment with basmasanil in participants aged 2–14 years old with dup15q syndrome followed by a 2-year optional open-label extension). LB served on an advisory board to Kingdom therapeutics in 2022., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Internalising symptoms are elevated in autism compared to the general population. Few studies have investigated emotional dysregulation (ED) as a potential mediator between specific transdiagnostic processes and anxiety and depression symptoms in autistic youth. In a sample of 94 autistic young people aged 5-18 years referred to a specialist clinic for an autism evaluation, we tested the effects of ED as a mediator between cognitive inflexibility (CI), intolerance of uncertainty (IU) and alexithymia with anxiety and depression symptoms, using structural equation modelling. Effect sizes were compared to a non-autistic comparison group (n = 84). CI and alexithymia did not significantly predict depression symptoms in autistic young people, directly nor via ED. Relationships between CI/alexithymia and depression were fully mediated by ED in the non-autistic sample. There was a direct effect of CI on anxiety in the non-autistic group but not in those with a diagnosis. IU predicted depression symptoms in the autism group; and ED mediated this relationship only in those who did not receive a diagnosis. IU directly predicted anxiety in both groups and this relationship did not occur via ED. The finding of a direct pathway from IU to anxiety and depression in autistic youth is consistent with the literature. The finding that CI did not predict anxiety or depression in those with autism is novel, as was the finding that ED mediated relationships between alexithymia and anxiety/depression symptoms in both samples. The findings may have important implications for the delivery of psychological interventions for autistic youth., (© 2024. The Author(s).)

The presence of an intellectual disability (ID) alongside autism is considered to increase the risk for mental health and behavior problems in children and adolescents. Existing evidence is restricted by looking at ID as a categorical classification. The study aimed to examine the association of cognitive and adaptive behavior skills with internalizing and externalizing problems in a large sample of autistic children and adolescents, across a wide range of cognitive skills. Participants were 2759 children and adolescents aged between 4 and 18 years recruited as part of the Simons Simplex Collection (SSC), of whom 709 (approximately 25%) had ID. Multiple regression models examined associations of internalizing and externalizing problems with cognitive and adaptive skills (communication, daily living, and socialization skills). Cognitive skills were not associated with externalizing problems but were associated with more internalizing problems in autistic children without ID (Cog β: 0.126). All adaptive skill domains were inversely associated with externalizing (Communication β: -0.145; Daily-Living β: -0.132; Socialization β: -0.289) and internalizing problems (Communication β: -0.074; Daily-Living β: -0.064; Socialization β: -0.213) in those without ID. Daily living (β: -0.158) and socialization skills (β: -0.104) were inversely correlated with externalizing problems in autistic children with ID, while only socialization problems (β: -0.099) were associated with internalizing problems in this group. Socialization skills were systematically associated with internalizing and externalizing problems across all levels of cognitive functioning. Supporting social skills development may benefit all aspects of child mental health, while recognizing that children with higher cognitive skills are more vulnerable to internalizing problems might assist with earlier identification of these problems., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Objective: To compare efficacy and side effect profile data on conservative, behavioral, pharmacological, and surgical treatments used for pediatric saliva control., Study Design: A cohort study of children (n = 483) referred to a specialty Saliva Control service between May 2014 and November 2019 was performed, using quantitative data from pretreatment and post-treatment questionnaires (the Drooling Impact Scale [DIS], Drooling Rating Scale [DRS]) and recording of side effects. Overall, 483 children were included; treatment choices were based on published international guidelines., Results: The greatest improvement was seen after intraglandular botulinum toxin A (BTX-A) injections (n = 207; 551 courses; mean DIS change, 34.7; 95% CI = 29.2-35.7) or duct transpositional surgery (n = 31; mean change in DIS, 29.0; 95% CI, 22.3-35.7). Oral anticholinergics were associated with good outcomes, with no significant statistical difference between glycopyrronium bromide (n = 150; mean DIS change, 21.5; 95% CI, 19.1-24.0) or trihexyphenidyl (n = 87; mean DIS change, 22.4; 95% CI, 18.9-25.8). Inhaled ipratropium bromide was not as efficacious (n = 80; mean DIS change, 11.1; 95% CI, 8.9-13.3). Oromotor programs were used in a selected group with reliable outcomes (n = 9; mean DIS change, 13.0). Side effects were consistent with previous studies. Overall, in cases of milder severity, enterally administered therapies provided a good first-line option. With more severe problems, BTX-A injections or saliva duct transpositional surgery were more effective and well tolerated., Conclusions: We describe a large, single-center pediatric saliva control cohort, providing direct comparison of the efficacy and side effect profiles for all available interventions and inform clinical practice for specialists when considering different options. BTX-A injections or saliva duct transpositional surgery seem to be more effective for saliva control that is more severe., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship., Objective: To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities., Design, Setting, Participants: A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n  = 155) or treatment as usual arm ( n  = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle., Intervention: Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic., Main Outcome Measure: The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge., Results: We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p  = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p  = 0.014) and -11.53 (95% CI -26.97 to 3.91, p  = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively ( p  = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention., Limitations: There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention., Conclusions: Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks., Future Work: Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes., Study Registration: This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information.

Developmental regression describes when a child loses previously established skills, such as the ability to speak words and is most recognised in neurodevelopmental conditions including Autism; Developmental Epileptic Encephalopathies, such as Landau Kleffner syndrome, and genetic conditions such as Rett syndrome and Phelan McDermid syndrome. Although studies have reported developmental regression for over 100 years, there remain significant knowledge gaps within and between conditions that feature developmental regression. The certainty of evidence from earlier work has been limited by condition-specific studies, retrospective methodology, and inconsistency in the definitions and measures used for classification. Given prior limitations in the field, there is a paucity of knowledge about neurocognitive mechanisms, trajectories and outcomes for children with developmental regression, and their families. Here we provide a comprehensive overview, synthesise key definitions, clinical measures, and aetiological clues associated with developmental regression and discuss impacts on caregiver physical and mental health to clarify challenges and highlight future directions in the field., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness., Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial., Setting: Twenty-one hospitals in the UK., Participants: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308., Intervention: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment., Main Outcome Measure: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended., Secondary Outcome Measures: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data., Results: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG., Conclusions: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis., Trial Registration Number: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925., Competing Interests: Competing interests: MI was a trainee member on the NIHR Efficacy and Mechanism Evaluation Programme Funding Committee from October 2020 to October 2021. MA has received a grant from the NIHR in the last 36 months, for research unrelated to the submitted work. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines; all funds have been paid to his institute. Ava Easton is Chief Executive of the Encephalitis Society, which has previously received grants from CSL Behring (UK). Ming Lim has received grants from the GOSH charity, Boston Children’s Hospital Research Fund and Action Medical Research in the last 36 months, all for research unrelated to the submitted work. Ming Lim is co-chair of the European Paediatric Neurology Education and Training Board and works for an institution which holds research accounts with Roche (Switzerland), Octapharma (Switzerland) and Novartis (Switzerland). Tom Solomon is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, NIHR Programme Grant for Applied Research, NIHR Global Health Research on Brain Infections and the European Union’s Horizon 2020 research and innovation program ZikaPLAN. Tom Solomon is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. Angela Vincent is a consultant for Aspen NewCo Inc and has received honoraria from UCB and Alexion. L-MY was a member of the NIHR Health Technology Assessment Efficient Study Designs from November 2015 to July 2016. Andrew J Pollard is chair of the Department of Health and Social Care’s Joint committee on Vaccines and Immunisation (JCVI) and was a member of WHO’s SAGE until 1 January 2022. Oxford University has entered a partnership with AstraZenenca on COVID-19 vaccines, but Andrew Pollard does not participate in the JCVI COVID-19 committee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)