Search

Abstract Background Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP. Methods CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting. Results While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064–1.142; C-statistic: 0.724–0.755). Conclusions To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.

Abstract Background Post-COVID Condition (PCC), also known as ‘Long COVID,’ refers to persistent symptoms following a coronavirus 2 (SARS-CoV-2) infection. The prevalence of PCC in children and adolescents varies, impacting multiple body systems and affecting daily functioning. Specialised paediatric hubs were established in England to address the needs of young individuals with PCC. Additional local services also emerged, yet patients report challenges accessing services. To better understand the landscape of paediatric PCC services, we used a novel methodology using a web-based systematic search. Methods A web-based search was conducted in July 2023 using DEVONagent Pro. Search terms related to Long COVID and Pediatrics in England. Eligible sources providing information on PCC services for children and young people were included. A supplementary manual search and NHS England Post-COVID Network were also consulted. Data extraction included service location, characteristics, and referral pathways. Population estimates were derived from UK Census data. Results Among 342 identified records, 27 services met eligibility criteria, distributed unevenly across regions. Specialised hubs covered 13 locations, while additional services were concentrated in the South of England and London. Services varied in team composition, age range treated, and support offered. A lack of standardised approaches for paediatric PCC was evident. Discussion We used a novel methodology for systematically mapping online resources, providing valuable insights into service accessibility and aiding the identification of potential gaps. We observed geographical disparities in access to paediatric PCC services and the absence of standardised approaches in managing symptoms. Given the challenges faced by young individuals seeking support for their PCC the need for equitable and standardised care became apparent. The study contributes to closing the research-practice gap and calls for further research to identify effective treatments for paediatric PCC, acknowledging the diversity of reported symptoms and the importance of tailored approaches.

Abstract Our previous study in children and young people (CYP) at 3- and 6-months post-infection showed that 12–16% of those infected with the Omicron (B.1.1.529) variant of SARS-CoV-2 met the research definition of Long Covid, with no differences between first-positive and reinfected CYP. The primary objective of the current study is to explore the impact of the Omicron variant of SARS-CoV-2 infection on young people 12 months post infection. 345 CYP aged 11–17 years with a first laboratory-confirmed infection with the Omicron variant and 360 CYP reinfected with the Omicron variant completed an online questionnaire assessing demographics, symptoms, and their impact shortly after testing and again at 3-, 6-and 12-months post-testing. Vaccination status was determined from information held at UKHSA. Comparisons between groups were made using chi-squared, Mann–Whitney U, and Kruskal–Wallis tests. The most common symptoms in first-positive and reinfected CYP 12-months post-testing were tiredness (35.7 and 33.6% respectively) and sleeping difficulties (27.5 and 28.3% respectively). Symptom profiles, severity and impact were similar in the two infection status groups. Overall, by 12-months, 17.4% of first-positives and 21.9% of reinfected CYP fulfilled the research consensus Long Covid definition (p = 0.13). 12-months post Omicron infection, there is little difference between first-positive and reinfected CYP with respect to symptom profiles and impact. Clinicians may not therefore need to consider number of infections and type of variant when developing treatment plans. Further studies are needed to assess causality of reported symptoms up to 12-months after SARS-CoV-2 infection.

BackgroundDespite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England.MethodsIt is hypothesised that families who receive psychological interventions through the drop-in services will show improved emotional and behavioural symptoms. Outcomes will be measured at baseline and at 6-month follow-up. The primary outcome is the difference in the total difficulties score on the Strengths and Difficulties Questionnaire (SDQ) reported by parent or child at 6 months. Secondary outcomes include self and parent reported Paediatric Quality of Life Inventory (PedsQL), self-reported depression (PHQ-9) and anxiety measures (GAD-7) and family satisfaction (CSQ-8).DiscussionThis trial aims to determine the clinical effectiveness of providing psychological support in the context of LTCs through drop-in mental health services at paediatric hospitals in England. These findings will contribute to policies and practice addressing mental health needs in children and young people with other long-term health conditions.Trial registrationISRCTN15063954, Registered on 9 December 2022.

BackgroundLittle is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories.Methods and findingsA matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias.ConclusionsOverall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.

Background Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants Children aged 9–17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was −2.29 points (95% confidence interval −3.86 to −0.71) in favour of therapy (effect size −0.31, 95% confidence interval −0.52 to −0.10). This effect was sustained throughout to the final follow-up at 18 months (−2.01 points, 95% confidence interval −3.86 to −0.15; effect size −0.27, 95% confidence interval −0.52 to −0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval −£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval −0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms Two serious, unrelated adverse events occurred in the control group. Limitations We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information. Plain language summary It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9–17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy. Scientific summary Background Tic disorders including Tourette syndrome and chronic tic disorders are common conditions that affect approximately 1% of the population in the UK. Young people with tics often report substantial impairment, thus it is important that they have access to evidence-based treatment. Face-to-face behavioural therapy (BT) such as exposure and response prevention (ERP) may be offered to some young people. However, due to a lack of trained therapists, there are often difficulties accessing BT, and there is a better need to understand the clinical and cost-effectiveness of the online delivery of such therapy. Objectives The primary objective of this study was to evaluate the clinical effectiveness of therapist-guided, parent-assisted, internet-based ERP BT for tics in young people with tic disorders compared to online psychoeducation. Secondary objectives included (1) optimising the design of the intervention, (2) undertaking an internal pilot, (3) evaluating cost-effectiveness, (4) establishing whether the efficacy is maintained longer term, (5) understanding the mechanisms of impact of the intervention and (6) identifying barriers to implementation. Methods We conducted an individually randomised (1 : 1 ratio), multicentre trial, with an internal pilot and embedded process evaluation. Participants were assigned to either receive online, remotely delivered, therapist- and parent-supported ERP for tics or online, remotely delivered, therapist- and parent-supported psychoeducation for tics. Participants were recruited from the two study sites, 16 patient identification centres in England or could self-refer online via the study webpage or via Tourettes Action (a national charity for tics). The inclusion criteria were age between 9 and 17 years, with tics assessed on the Yale Global Tic Severity Scale (YGTSS), able to provide written informed consent (parental consent for children aged < 16 years) and with a suitable device they could use to access the internet. Exclusion criteria included receiving a therapy for tics in the past 12 months, starting or stopping tic medication within the past 2 months and intellectual disability/substance use/anorexia nervosa/psychosis/suicidality, moderate/severe intellectual disability, risk to self or others or parent or young person unable to speak or read/write English. All potential participants attended a screening/baseline appointment at one of the two study centres. Participants who were eligible and consented were randomised into one of two study groups. In the intervention group participants received 10 weeks of the remotely delivered, therapist-guided ERP behaviour therapy. In the control group participants received 10 weeks of remotely delivered, therapist-guided psychoeducation about tics. Participants completed measures at the mid-treatment point (5 weeks) and at 3 and 6 months (this formed phase 1, per-protocol design). For phase 2 (a naturalist design), follow-up measures were obtained at 12 and 18 months. The primary outcome (at 3 months) was the total tic severity score (TTSS) on the YGTSS. Secondary outcomes included measures of tics (parent tic questionnaire), general difficulties (strengths and difficulties questionnaire), mood and anxiety (moods and feelings questionnaire and Spence Child Anxiety Scale), global functioning (Children’s Global Assessment Scale, Clinical Global Impressions-Improvement), adverse events, need for further treatment, treatment credibility and satisfaction and the Child and Adolescent Version of the Gilles de la Tourette Syndrome Quality of Life Scale. Quality of life [child health utility 9D (CHU9D)] and resource use (modified child and adolescent service use schedule) data were also collected for the economic evaluation. Follow-up assessments were completed online or via telephone/Webex videoconferencing (YGTSS). The trial internal pilot evaluated recruitment rate, engagement with the intervention and retention to the primary outcome at 9 months into the trial and the results were reported to the relevant oversight committees (Trial Steering Committees and Data Monitoring Committee). A sub-sample of parents and young people in the intervention arm, clinicians and therapists were interviewed to explore barriers/facilitators to implementation and refine the intervention for future use, which formed part of the mixed-methods process evaluation. The quantitative data for the process evaluation included intervention usage metrics, clinical and demographic trial data and therapist contacts. Intervention The intervention was delivered via Barninternetprojektet (Child Internet Project; Swedish digital platform) (BIP), a Swedish web-based digital platform. The BT intervention (ERP) was translated from the Swedish original intervention (BIP TIC), refined and adapted for UK use by our trial team. The active control intervention (psychoeducation) was created by our trial team. Both interventions consisted of 10 web-based chapters, designed to last 10 weeks. Participants had regular contact with a therapist during this time via messages that could be sent inside the treatment platform (resembling an email). The therapist’s role was to give specific feedback to motivate the patient and not to deliver therapeutic content. The young person and the parent/carer were provided with their own separate logins to the BIP platform. For both the intervention and the comparator, treatment completion was defined as completion of the first four child chapters. Results The trial recruited and retained participants exceeding the pre-specified criteria for the internal pilot and therefore proceeded to the full trial. In total 445 candidates signed up to the study and were assessed for eligibility, of which 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate and 47 were unable to contact family). This meant 224 participants were enrolled and randomly assigned (1 : 1) to either the ERP BT group (n = 112) or psychoeducation group (n = 112). The characteristics of the two groups were similar at baseline. The enrolled patients were mostly male (n = 177; 79%) and of white ethnicity (n = 195; 87%). Only 13% of participants were receiving tic medication. Adherence to the intervention was good in 99 (88%) of the 112 participants in the ERP group, and 105 (94%) of the 112 participants in the psychoeducation group were classified as treatment completers (i.e. completing at least the first four chapters). Retention to the primary outcome at the 3-month primary end point (90%) and 6-month follow-up (> 80%) was excellent. Retention to the primary outcome measure remained high at 12 months (81% in both arms) and 18 months (> 79% in both arms). The primary analysis showed that participants in the ERP group [16% reduction, standard deviation (SD) 1.1] had a greater decrease in tics than those in the psychoeducation group (6% reduction, SD 1.0) at 3 months (primary end point). The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was −2.29 points [95% confidence interval (CI) −3.86 to −0.71] in favour of ERP, with an effect size of −0.31 (95% CI −0.52 to −0.10). This effect was sustained at 6 months, with a mean decrease of 6.9 points (24%, SD 1.2) in the ERP group versus 3.4 points (12%, SD 1.0) in the psychoeducation group. For phase 2, participants in the ERP group continued to have a greater decrease in tics than the control group. The estimated mean difference in YGTSS-TTSS between groups adjusting for baseline and site at 12 months was −2.64 points (95% CI −4.48 to −0.79), with an effect size of −0.36 (95% CI −0.61 to −0.11), at 18 months it was −2.01 points (95% CI −3.86 to −0.15), with an effect size of −0.27 (95% CI −0.52 to −0.02), in favour of the ERP group. In addition, extended follow-up showed those receiving online ERP compared with online psychoeducation had reduced scores for low mood and anxiety at 12 and 18 months and superior tic-specific quality of life, with the largest effects seen at 18 months. The direct cost of the intervention was £155 per person, including £104.57 for the online platform, supervision and training and a mean variable cost of £50.43 per participant for therapist time in the trial. At 18 months, using proxy parent-completed CHU9D responses, there were a mean additional 0.040 (95% CI −0.004 to 0.083) quality-adjusted life-years (QALYs) per participant in the ERP group compared with psychoeducation, with an addition mean cost per participant of £662 (95% CI −£59 to £1384). The incremental cost-effectiveness ratio in the primary analysis was £16,708 per QALY gained from a health and social care cost perspective at 18 months. In the 10-year long-term decision model, online ERP cost £537 less per participant than face-to-face BT and resulted in 0.02 fewer QALYs. Two serious adverse events (SAEs) occurred (hospital attendance due to one ‘collapse’ and one ‘tic attack’), both in the active control psychoeducation group, neither of which were related to the study intervention. The process evaluation found that the ERP intervention was implemented with high fidelity, and participants found the intervention acceptable and satisfactory. Engagement was high, with child participants completing an average of 7.5/10 chapters and 99/112 (88.4%) participants completing the minimum of the first four chapters (the predefined threshold for effective dose). Parental engagement was the only significant independent predictor of child engagement. Improvement in tic severity and overall clinical condition was not moderated by the relationship between demographic or baseline clinical factors and engagement and no mediators were found. However, level of parental engagement was associated with overall clinical improvement, and this relationship was illuminated by the qualitative data. Conclusion Implications for health care The findings demonstrate that online, therapist-supported ERP for young people with chronic tic disorders is clinically effective at reducing tic severity. Therefore, this is an efficient public mental health approach to supporting young people with tics. The intervention can be delivered at lower cost than standard face-to-face BT and may also result in improved service efficiencies, allowing a greater number of young people to access evidence-based care. Future research implications Further ‘field trials’ should be conducted to explore the clinical and service implications of delivering the intervention in real-world settings. Given that online interventions are context dependent, exploring the validity of these findings in different cultures/countries is important. Future research should explore where online, therapist-supported ERP best fits in the tic disorder care pathway and how online and face-to-face therapy can be best combined (e.g. non-responders to online ERP are ‘stepped up’ to face-to-face therapy). Trial registrations This trial is registered as ISRCTN70758207 and ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

Abstract Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Abstract Background To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status. Methods Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11–17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting. Results A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130). Conclusions We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.

Abstract Background Paediatric patients being treated for long-term physical health conditions (LTCs) have elevated mental health needs. However, mental health services in the community are difficult to access in the usual course of care for these patients. The Lucy Project – a self-referral drop-in access point—was a program to address this gap by enrolling patients for low-intensity psychological interventions during their treatment for LTCs. In this paper, we evaluate the cost-effectiveness of the Lucy Project. Methods Using a pre-post design, we evaluate the cost-effectiveness of the intervention by calculating the base-case incremental cost-effectiveness ratio (ICER) using outcomes data and expenses recorded by project staff. The target population was paediatric patients enrolled in the program with an average age of 9 years, treated over a time horizon of 6 months. Outcome data were collected via the Paediatric Quality of Life Inventory, which was converted to health utility scores using an instrument found in the literature. The QALYs were estimated using these health utility scores and the length of the intervention. We calculate a second, practical-case incremental cost-effectiveness ratio using streamlined costing figures with maximum capacity patient enrolment within a one-year time horizon, and capturing lessons learned post-trial. Results The base-case model showed an ICER of £21,220/Quality Adjusted Life Years (QALY) gained, while the practical model showed an ICER of £4,359/QALY gained. The practical model suggests the intervention garners significant gains in quality of life at an average cost of £309 per patient. Sensitivity analyses reveal use of staff time was the greatest determinant of the ICER, and the intervention is cost-effective 75% of the time in the base-case model, and 94% of the time in the practical-case model at a cost-effectiveness threshold of £20,000/QALY gained. Conclusions We find the base-case intervention improves patient outcomes and can be considered cost-effective according to the National Institute for Health and Care Excellence (NICE) threshold of £20,000—£30,000/QALY gained, and the practical-case intervention is roughly four times as cost-effective as the base-case. We recommend future studies incorporate a control group to corroborate the effect size of the intervention.

Background: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described. Purpose: (1) to describe the characteristics of children aged 11–17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom’s largest research study of Long COVID in children (CLoCk). Design: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk. Results: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk. Conclusions: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group.

BackgroundDuring the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.Methods and findingsParticipants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas.ConclusionsWe demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.

BackgroundLittle is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no prospective follow-up to establish the pattern of symptoms over a 6-month time period.MethodsA non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11-17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP.ResultsThree months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10-25% at testing to ConclusionsIn CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.

Background: Although 99% of children and young people have been exposed to SARS-CoV-2, the long-term prevalence of post-COVID-19 symptoms in young people is unclear. The aim of this study is to describe symptom profiles 12 months after SARS-CoV-2 testing. Method: A matched cohort study of a national sample of 20,202 children and young people who took a SARS-CoV-2 PCR test between September 2020 and March 2021. Results: 12 months post-index-test, there was a difference in the number of symptoms reported by initial negatives who never tested positive (NN) compared to the other three groups who had at least one positive test (p < 0.001). Similarly, 10.2% of the NN group described five-plus symptoms at 12 months compared to 15.9–24.0% in the other three groups who had at least one positive test. The most common symptoms were tiredness, sleeping difficulties, shortness of breath, and headaches for all four groups. For all these symptoms, the initial test positives with subsequent reports of re-infection had higher prevalences than other positive groups (p < 0.001). Symptom profiles, mental health, well-being, fatigue, and quality of life did not vary by vaccination status. Conclusions: Following the pandemic, many young people, particularly those that have had multiple SARS-CoV-2 positive tests, experience a range of symptoms that warrant consideration and potential investigation and intervention.

Abstract Background Mental health disorders in the context of long-term conditions in children and young people are currently overlooked and undertreated. Evidence-based psychological treatments for common childhood mental health disorders (anxiety, depression and disruptive behaviour disorders) have not been systematically evaluated in young people with epilepsy despite their high prevalence in this population. The aim of this multi-site randomised controlled trial is to determine the clinical and cost-effectiveness of adding a modular psychological intervention to usual care for the mental health disorders in comparison to assessment-enhanced usual care alone. Methods In total, 334 participants aged 3–18 years attending epilepsy services will be screened for mental health disorders with the Strengths and Difficulties Questionnaire (SDQ) and the diagnostic Development and Wellbeing Assessment (DAWBA). Those identified as having a mental health disorder and consenting to the trial will be randomised to either receive up to 22 sessions of the modular psychological intervention (MATCH-ADTC) delivered over the telephone over 6 months by non-mental health professionals in addition to usual care or to assessment-enhanced usual care alone. Outcomes will be measured at baseline, 6 months and 12 months post-randomisation. It is hypothesised that MATCH-ADTC plus usual care will be superior to assessment-enhanced usual care in improving emotional and behavioural symptoms. The primary outcome is the SDQ reported by parents at 6 months. Secondary outcomes include parent-reported mental health measures such as the Revised Children’s Anxiety and Depression Scale, quality of life measures such as the Paediatric Quality of Life Inventory and physical health measures such as the Hague Seizure Severity Scale. Outcome assessors will be blinded to group assignment. Qualitative process evaluations and a health economic evaluation will also be completed. Discussion This trial aims to determine whether a systematic and integrated approach to the identification and treatment of mental health disorders in children and young people with epilepsy is clinically and cost-effective. The findings will contribute to policies and practice with regard to addressing mental health needs in children and young people with other long-term conditions. Trial registration ISRCTN ISRCTN57823197 . Registered on 25 February 2019.

Abstract Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Abstract Background Children with chronic health conditions and their parents are at greater risk of developing emotional and behavioural problems compared to their physically healthy peers. The psychological impact on parents is crucial to understand given the relationship between parental mental health and child emotional and behavioural difficulties. This study was part of a broader research project examining the acceptability, feasibility and impact of a ‘Mental Health and Psychological Wellbeing Drop‐in Centre’ in a paediatric hospital providing access to support and intervention for children and their families. This paper aimed to investigate the impact of the centre on parents (n = 148). Methods Parental anxiety and depression were assessed using the GAD‐7 and PHQ‐9 at baseline and 6‐month post‐baseline. Child mental health was assessed using the parent‐report Strengths and Difficulties Questionnaire (SDQ). If parents had significant mental health needs, a brief intervention/signposting to relevant services was provided. Results At baseline, 48% of parents scored above clinical threshold for anxiety and 41% for depression, and parent reported child SDQ scores were correlated with parental anxiety and parental low mood. Self‐reported parental anxiety and low mood decreased at 6‐months post‐baseline (parental anxiety: mean decrease = 2.29 [1.22–3.36], d = 0.38; parental low mood: mean decrease = 1.81 [0.64–3.00], d = 0.28). There were no significant correlations between change in parent reported child wellbeing and changes in parental low mood and anxiety between baseline and 6‐month post‐baseline. Conclusions Assessing and providing a brief treatment to address the mental health needs of parents of children with comorbidity may bring important benefits. It is recommended that children's mental health services consider assessment of parental mental health as part of routine care.

The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale “European Multicentre Tics in Children Study” (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (rs = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (rs = 0.24), obsessive–compulsive symptoms (rs = 27) as well as internalizing symptoms (rs = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors “motor tics” and “phonic tics,” but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial.

Background: Although mental health difficulties can severely complicate the lives of children and young people (CYP) with long-term physical conditions (LTCs), there is a lack of evidence about the effectiveness of interventions to treat them. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of interventions aiming to improve the mental health of CYP with LTCs (review 1) and explore the factors that may enhance or limit their delivery (review 2). Data sources: For review 1, 13 electronic databases were searched, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Science Citation Index. For review 2, MEDLINE, PsycINFO and CINAHL were searched. Supplementary searches, author contact and grey literature searches were also conducted. Review methods: The first systematic review sought randomised controlled trials (RCTs) and economic evaluations of interventions to improve elevated symptoms of mental ill health in CYP with LTCs. Effect sizes for each outcome were calculated post intervention (Cohen’s d). When appropriate, random-effects meta-analyses produced pooled effect sizes (d). Review 2 located primary qualitative studies exploring experiences of CYP with LTCs, their families and/or practitioners, regarding interventions aiming to improve the mental health and well-being of CYP with LTCs. Synthesis followed the principles of metaethnography. An overarching synthesis integrated the findings from review 1 and review 2 using a deductive approach. End-user involvement, including topic experts and CYP with LTCs and their parents, was a feature throughout the project. Results: Review 1 synthesised 25 RCTs evaluating 11 types of intervention, sampling 12 different LTCs. Tentative evidence from seven studies suggests that cognitive–behavioural therapy interventions could improve the mental health of CYP with certain LTCs. Intervention–LTC dyads were diverse, with few opportunities to meta-analyse. No economic evaluations were located. Review 2 synthesised 57 studies evaluating 21 types of intervention. Most studies were of individuals with cancer, a human immunodeficiency virus (HIV) infection or mixed LTCs. Interventions often aimed to improve broader mental health and well-being, rather than symptoms of mental health disorder. The metaethnography identified five main constructs, described in an explanatory line of argument model of the experience of interventions. Nine overarching synthesis categories emerged from the integrated evidence, raising implications for future research. Limitations: Review 1 conclusions were limited by the lack of evidence about intervention effectiveness. No relevant economic evaluations were located. There were no UK studies included in review 1, limiting the applicability of findings. The mental health status of participants in review 2 was usually unknown, limiting comparability with review 1. The different evidence identified by the two systematic reviews challenged the overarching synthesis. Conclusions: There is a relatively small amount of comparable evidence for the effectiveness of interventions for the mental health of CYP with LTCs. Qualitative evidence provided insight into the experiences that intervention deliverers and recipients valued. Future research should evaluate potentially effective intervention components in high-quality RCTs integrating process evaluations. End-user involvement enriched the project. Study registration: This study is registered as PROSPERO CRD42011001716. Funding: The National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

BackgroundTelephone cognitive–behaviour therapy (TCBT) may be a cost-effective method for improving access to evidence-based treatment for obsessive–compulsive disorder (OCD) in young people.AimsEconomic evaluation of TCBT compared with face-to-face CBT for OCD in young people.MethodRandomised non-inferiority trial comparing TCBT with face-to-face CBT for 72 young people (aged 11 to 18) with a diagnosis of OCD. Cost-effectiveness at 12-month follow-up was explored in terms of the primary clinical outcome (Children's Yale-Brown Obsessive-Compulsive Scale, CY-BOCS) and quality-adjusted life-years (QALYs) (trial registration: ISRCTN27070832).ResultsTotal health and social care costs were higher for face-to-face CBT (mean total cost £2965, s.d. = £1548) than TCBT (mean total cost £2475, s.d. = £1024) but this difference was non-significant (P = 0.118). There were no significant between-group differences in QALYs or the CY-BOCS and there was strong evidence to support the clinical non-inferiority of TCBT. Cost-effectiveness analysis suggests a 74% probability that face-to-face CBT is cost-effective compared with TCBT in terms of QALYs, but the result was less clear in terms of CY-BOCS, with TCBT being the preferred option at low levels of willingness to pay and the probability of either intervention being cost-effective at higher levels of willingness to pay being around 50%.ConclusionsAlthough cost-effectiveness of TCBT was sensitive to the outcome measure used, TCBT should be considered a clinically non-inferior alternative when access to standard clinic-based CBT is limited, or when patient preference is expressed.Declaration of interestD.M.-C. reports research grants from the Swedish Research Council (Vetenskapsrådet), the Swedish Research Council for Health, working life and welfare (Forte), the US National Institute of Mental Health (NIMH), the UK National Institute of Health Research (NIHR), as well as royalties from Wolters Kluwer Health and Elsevier, all unrelated to the submitted work.

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment. Objective: To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2). Data Sources: For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013. Review/research methods: For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged

Background: Epilepsy is one of the most common chronic paediatric conditions. Children and young people with epilepsy are at a significantly higher risk of developing mental health problems relative to the general population, yet the majority of these problems are unrecognised and under-treated in clinical practice. Although there is little epilepsy-specific guidance as to what interventions to use, researchers suggest there is no reason why clinicians should not be using the evidence base. Given the poor prognosis of untreated mental health difficulties, this cohort study sought to identify what psychological treatment young people with epilepsy with mental health needs receive in routine practice. Methods: Participants were children and young people aged 3 to 18 attending paediatric neurology clinics. The parents of those children who met threshold for impairing symptoms on the Strengths and Difficulties questionnaire were asked to complete the Development and Well-being Assessment (DAWBA), an online clinical assessment designed to generate psychiatric diagnoses. Participants who met clinical threshold for a disorder according to the DAWBA were provided with a bespoke measure asking questions regarding their experience with treatment for mental health support. Results: 16 of the 46 parents who completed the DAWBA reported that they had experienced previous or current support for their child’s mental health difficulties. The mental health support offered to families was highly variable, inadequate and often not clearly compliant with existing UK National Institute for Health and Clinical Excellence (NICE) guidelines for mental health treatment in children and young people. Conclusions: The present study demonstrates the inconsistency and inadequacy of mental health provision for children and young people with epilepsy. Future work should explore reasons for the treatments offered failing to adhere to existing guidance for mental health difficulties in children, as well as possible solutions to this.