Long-term clinical and cost-effectiveness of a therapist-supported online remote behavioural intervention for tics in children and adolescents: extended 12- and 18-month follow-up of a single-blind randomised controlled trial.

BACKGROUND: Little is known about the long-term effectiveness of behavioural therapy for tics. We aimed to assess the long-term clinical and cost-effectiveness of online therapist-supported exposure and response prevention (ERP) therapy for tics 12 and 18 months after treatment initiation. METHODS: ORBIT (online remote behavioural intervention for tics) was a two-arm (1:1 ratio), superiority, single-blind, multicentre randomised controlled trial comparing online ERP for tics with online psychoeducation. The trial was conducted across two Child and Adolescent Mental Health Services in England. Participants were recruited from these two sites, across other clinics in England, or by self-referral. This study was a naturalistic follow-up of participants at 12- and 18-month postrandomisation. Participants were permitted to use alternative treatments recommended by their clinician. The key outcome was the Yale Global Tic Severity Scale Total Tic Severity Score (YGTSS-TTSS). A full economic evaluation was conducted. Registrations are ISRCTN (ISRCTN70758207); ClinicalTrials.gov (NCT03483493). RESULTS: Two hundred and twenty-four participants were enrolled: 112 to ERP and 112 to psychoeducation. The sample was predominately male (177; 79%) and of white ethnicity (195; 87%). The ERP intervention reduced baseline YGTSS-TTSS by 2.64 points (95% CI: -4.48 to -0.79) with an effect size of -0.36 (95% CI: -0.61 to -0.11) after 12 months and by 2.01 points (95% CI: -3.86 to -0.15) with an effect size of -0.27 (95% CI -0.52 to -0.02) after 18 months, compared with psychoeducation. Very few participants (<10%) started new tic treatment during follow-up. The cost difference in ERP compared with psychoeducation was £304.94 (-139.41 to 749.29). At 18 months, the cost per QALY gained was £16,708 for ERP compared with psychoeducation. CONCLUSIONS: Remotely delivered online ERP is a clinical and cost-effective intervention with durable benefits extending for up to 18 months. This represents an efficient public mental health approach to increase access to behavioural therapy and improve outcomes for tics.

Patients' experience of accessing support for tics from primary care in the UK: an online mixed-methods survey.

BACKGROUND: Tics are common in children and young people and may persist into adulthood. Tics can cause challenges with social, occupational, physical, and academic functioning. The current study explores the perceptions of adults with tics and parents/carers of young people with tics regarding their experience of accessing support from professionals in primary care in the UK. METHODS: Two online cross-sectional surveys were completed by 33 adults with tics and 94 parents/carers of children with tics. Participants were recruited across three online tic support groups. Tic specialist psychologists, academic researchers, and people with lived experience of tics provided feedback on the surveys before they were made available online. Mixed-method analyses were conducted on the surveys. Qualitative data from the free-text responses were analysed using thematic analysis and triangulated with quantitative findings where appropriate. RESULTS: While some participants felt supported by general practitioners (GPs), many felt dismissed. The impact of tics was not always explored, nor information on tics provided, during the consultation. Although 78.7% of participants were referred to secondary care for their tics, some struggled to get the referral. Within secondary care, most adult respondents were assessed by neurologists whilst young people were typically assessed by paediatricians or psychiatrists. Most of these secondary care clinicians did not specialise in tic disorders, with only 27.9% of participants being assessed by tic specialists. Mode waitlist time was 3-6 months for young people and longer for adult respondents. Some participants were referred to multiple secondary care services, spanning neurology, paediatrics, and psychiatry, with each stating that they do not provide support for tics. 21% of participants mentioned being discharged from secondary care with no ongoing support. Almost one-third of respondents accessed support within private healthcare. CONCLUSIONS: Generally, more negative than positive experiences were reported. Possible contributing factors included a lack of clear tic referral pathways, long waitlists, a lack of information about tics provided in primary care appointments and a lack of support offered following diagnosis by secondary care services, together with poor access to tic specialist clinicians. This study highlights areas where improvements to UK services for tics can be made.

The COVID-19 pandemic and its impact on tic symptoms in children and young people: a prospective cohort study.

To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9-17 years) randomised to the control arm of the "ORBIT-Trial" (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months' post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms.

Fidelity of Delivery and Contextual Factors Influencing Children's Level of Engagement: Process Evaluation of the Online Remote Behavioral Intervention for Tics Trial.

BACKGROUND: The Online Remote Behavioral Intervention for Tics (ORBIT) study was a multicenter randomized controlled trial of a complex intervention that consisted of a web-based behavioral intervention for children and young people with tic disorders. In the first part of a two-stage process evaluation, we conducted a mixed methods study exploring the reach, dose, and fidelity of the intervention and contextual factors influencing engagement. OBJECTIVE: This study aims to explore the fidelity of delivery and contextual factors underpinning the ORBIT trial. METHODS: Baseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (N=112). The experiences of being in the intervention were explored through semistructured interviews with children (n=20) and parent participants (n=20), therapists (n=4), and referring clinicians (n=6). A principal component analysis was used to create a comprehensive, composite measure of children and young people's engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices, including chapters accessed, number of pages visited, and number of log-ins. The engagement factor score was used as the dependent variable in a multiple linear regression analysis with various contextual variables as independent variables to assess if there were any significant predictors of engagement. RESULTS: The intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. The engagement was high, with child participants completing an average of 7.5 of 10 (SD 2.7) chapters, and 88.4% (99/112) of participants completed the minimum of the first four chapters-the predefined threshold effective dose. Compared with the total population of children with tic disorders, participants in the sample tended to have more educated parents and lived in more economically advantaged areas; however, socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site versus the Nottingham site (P=.01), self-referred versus clinic referred (P=.04), higher parental engagement as evidenced by the number of parental chapters completed (n=111; ρ=0.73; P<.001), and more therapist time for parents (n=111; ρ=0.46; P<.001). A multiple linear regression indicated that parents' chapter completion (ß=.69; t110=10.18; P<.001) and therapist time for parents (ß=.19; t110=2.95; P=.004) were the only significant independent predictors of child engagement factor scores. CONCLUSIONS: Overall, the intervention had high fidelity of delivery and was evaluated positively by participants, although reach may have been constrained by the nature of the randomized controlled trial. Parental engagement and therapist time for parents were strong predictors of intervention implementation, which has important implications for designing and implementing digital therapeutic interventions in child and adolescent mental health services. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-019-3974-3.

The Effectiveness of Web-Based Interventions Delivered to Children and Young People With Neurodevelopmental Disorders: Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of certain neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), has been increasing over the last four decades. Nonpharmacological interventions are available that can improve outcomes and reduce associated symptoms such as anxiety, but these are often difficult to access. Children and young people are using the internet and digital technology at higher rates than any other demographic, but although Web-based interventions have the potential to improve health outcomes in those with long-term conditions, no previous reviews have investigated the effectiveness of Web-based interventions delivered to children and young people with neurodevelopmental disorders. OBJECTIVE: This study aimed to review the effectiveness of randomized controlled trials (RCTs) of Web-based interventions delivered to children and young people with neurodevelopmental disorders. METHODS: Six databases and one trial register were searched in August and September 2018. RCTs were included if they were published in a peer-reviewed journal. Interventions were included if they (1) aimed to improve the diagnostic symptomology of the targeted neurodevelopmental disorder or associated psychological symptoms as measured by a valid and reliable outcome measure; (2) were delivered on the Web; (3) targeted a youth population (aged ≤18 years or reported a mean age of ≤18 years) with a diagnosis or suspected diagnosis of a neurodevelopmental disorder. Methodological quality was rated using the Joanna Briggs Institute Critical Appraisal Checklist for RCTs. RESULTS: Of 5140 studies retrieved, 10 fulfilled the inclusion criteria. Half of the interventions were delivered to children and young people with ASDs with the other five targeting ADHD, tic disorder, dyscalculia, and specific learning disorder. In total, 6 of the 10 trials found that a Web-based intervention was effective in improving condition-specific outcomes or reducing comorbid psychological symptoms in children and young people. The 4 trials that failed to find an effect were all delivered by apps. The meta-analysis was conducted on five of the trials and did not show a significant effect, with a high level of heterogeneity detected (n=182 [33.4%, 182/545], 5 RCTs; pooled standardized mean difference=-0.39; 95% CI -0.98 to 0.20; Z=-1.29; P=.19 [I2=72%; P=.006]). CONCLUSIONS: Web-based interventions can be effective in reducing symptoms in children and young people with neurodevelopmental disorders; however, caution should be taken when interpreting these findings owing to methodological limitations, the minimal number of papers retrieved, and small samples of included studies. Overall, the number of studies was small and mainly limited to ASD, thus restricting the generalizability of the findings. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews: CRD42018108824; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018108824.

Online remote behavioural intervention for tics in 9- to 17-year-olds: the ORBIT RCT with embedded process and economic evaluation.

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.

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 9­17 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.

Digital and remote behavioral therapies for treating tic disorders: Recent advances and next steps.

The rapid expansion of access to and engagement with digital technology over the past 15 years has transformed the potential for remote delivery of evidence-based digital health interventions (DHIs). Digital and remote behavioral interventions have the potential to address current gaps in the provision of evidence-based therapies in healthcare services. As the lack of access to behavioral treatments for people with tic disorders is a pressing issue across the world, there is great potential for DHIs to close this treatment gap. Here, we present a critical synthesis of the recent key advances in the field of digitally delivered, remote therapy for tics, outlining the research evidence for the clinical and cost-effectiveness and acceptability of digital or remotely delivered therapy. We found five trials aimed at reducing tic severity in children and young people and one trial for adults. The evidence supports the clinical utility of DHIs to deliver tic therapies, which shows promise in being clinically efficacious compared to an active control. Furthermore, DHIs in trials show good adherence and engagement and are acceptable to patients. The role of human support (including therapists and parents for young people) is likely to be important to encourage adherence. DHIs, where the main therapeutic content is delivered via web-based chapters, are likely to reduce clinical time, and maintain intervention fidelity, but further research is required to understand cost-effectiveness. Despite utilizing randomized controlled trials, only two trials were sufficiently powered to address efficacy and only one trial explored contextual factors that may influence engagement. Moreover, only one trial followed patients for >12 months, thus further long-term follow-ups are required. Specifically, we note that despite an emerging evidence base, DHIs for tics are yet to be routinely implemented in healthcare provision in any country. Drawing on the existing evidence, we conclude by proposing a stepped care model, in which digital therapy is implemented as a widely accessible first-line treatment using a purely online or therapist-supported approach.

Therapist-supported online remote behavioural intervention for tics in children and adolescents in England (ORBIT): a multicentre, parallel group, single-blind, randomised controlled trial.

BACKGROUND: Exposure and Response Prevention (ERP) is a form of behavioural therapy for tics; however, its effectiveness remains uncertain. We aimed to evaluate the effectiveness of internet-delivered, therapist-supported, and parent-assisted ERP for treatment of tics in children and young people with Tourette syndrome or chronic tic disorder. METHODS: This multicentre, parallel group, single-blind, randomised controlled trial was conducted across two study sites in England. Participants were recruited via 16 patient identification centres, two study sites in England (Nottingham and London), or online self-referral. Eligible participants were aged 9-17 years, had Tourette syndrome or chronic tic disorder, had not received behavioural therapy for tics in the past 12 months or were about to start, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of more than 15 or more than 10 if they had only motor or vocal tics. Patients were excluded if they had started or stopped medication for tics within the past 2 months; had current alcohol or substance dependence, psychosis, suicidality, anorexia nervosa, or suspected moderate to severe intellectual disability; or presented an immediate risk to self or others; or the parent or carer was unable to speak, read, or write in English. Eligible patients were randomly assigned (1:1) by masked outcome assessors to receive 10 weeks of online, remotely delivered, therapist-supported ERP or psychoeducation (active control). Outcome assessors, statisticians, health economists, the trial manager, and the chief investigator were masked to group allocation. Patients were not directly informed of their allocation, but this could be established from the content once treatment commenced and the patients were not, therefore, considered masked to treatment. The primary outcome was YGTSS-TTSS 3 months after randomisation, and analysis was done in all randomised patients for whom data were available for each timepoint and outcome. Safety analysis was by intention to treat. Longer term follow-up is ongoing. This trial is registered with ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). FINDINGS: Between May 8, 2018, and Sept 30, 2019, we assessed 445 candidates for inclusion in the study. 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate, and 47 unable to contact family). 224 participants were enrolled and randomly assigned to ERP (n=112) or psychoeducation (n=112). The enrolled patients were mostly male (n=177; 79%) and of White ethnicity (n=195; 87%). 11 patients were lost to follow-up 3 months after randomisation in the ERP group, compared with 12 patients in the psychoeducation group. Mean YGTSS-TTSS at 3 months after randomisation was 23·9 (SD 8·2) in the ERP group and 26·8 (7·3) in the psychoeducation group. The mean total decrease in YGTSS-TTSS at 3 months was 4·5 (16%, SD 1·1) in the ERP group versus 1·6 (6%, 1·0) in the psychoeducation group. The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was -2·29 points (95% CI -3·86 to -0·71) in favour of ERP, with an effect size of -0·31 (95% CI -0·52 to -0·10). Two serious adverse events occurred (one collapse and one tic attack), both in the psychoeducation group, neither of which were related to study treatment. INTERPRETATION: ERP is an effective behavioural therapy for tics. Remotely delivered, online ERP with minimal therapist contact time represents an efficient public mental health approach to improve access to behavioural therapy for tics in children and adolescents. FUNDING: National Institute for Health Research and Health and Technology Assessment.

Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people.

BACKGROUND: Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT). METHOD: We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online. RESULTS: Data were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials. CONCLUSION: An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery. TRIAL REGISTRATION: The ORBIT trial is registered with ISRTCN ( ISRCTN70758207 ) Registered on March 20, 2018. and ClinicalTrials.gov ( NCT03483493 ). Registered on March 30, 2018.

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Decompression injuries occur on account of the special hyperbaric effects during the emerge phase and require superior therapeutic knowledge. Vitally important is emergency treatment with high concentrated oxygen at an early stage. Sever decompression injuries require oxygenation in a hyperbaric treatment chamber.