Experience of CBT in adults with ADHD: a mixed methods study.

Introduction: The National Institute for Health and Care Excellence (NICE) recommends Cognitive-Behavioural therapy (CBT) as the psychotherapeutic treatment of choice for adults with Attention Deficit Hyperactivity Disorder (ADHD) in the UK. However, the literature often refers to adapted CBT programs tailored for ADHD and provides limited insight into how adults with ADHD experience and perceive this form of treatment in routine clinical practice. Methods: This mixed-methods study aims to explore ADHD individuals' experience and perception of CBT delivered in routine clinical practice, to gain a better understanding of this treatment's helpfulness and perceived effectiveness. Results: A survey (n=46) and semi-structured in-depth interviews (n=10) were conducted to explore the experience of CBT and its perceived effectiveness in managing ADHD. The interviews were analysed using thematic analysis and the survey was synthesised using descriptive narratives. The thematic analysis highlighted three key themes: difficulties with the CBT framework, difficulties with CBT therapists, and consequences of CBT. The survey highlighted similar findings. Participants described the CBT framework as, generic, rigid, and too short, and described the CBT therapist as unspecialised, unempathetic, and not sufficiently adapting CBT to ADHD-related difficulties. Discussions: Overall, participants found non-adapted, generic CBT in the UK to be unhelpful, overwhelming, and at times harmful to their mental well-being. Therefore, it is necessary for clinical bodies in the UK, while following the indicated NICE guidelines, to be mindful of adapting CBT delivery of CBT, to be most effective for people with ADHD and to mitigate potential harm.

The impacts associated with having ADHD: an umbrella review.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) affects up to 5% of the population and is characterised by symptoms of impulsivity, hyperactivity and inattention. These symptoms are significantly impairing and carry additional risks for children and adults with ADHD, including negative mental health (e.g. depression), physical health (e.g. obesity) and societal outcomes (e.g. imprisonment, divorce). Very few studies have attempted to synthesise these risks in one publication due to the breadth of evidence published on the adverse outcomes of ADHD. Methods: An umbrella review was performed to identify reviews (systematic, meta-analysis and narrative) that investigate the risks arising from having ADHD. We conducted a narrative synthesis of the findings and conducted a quality review of the included publications. Results: Upon searching five databases, 16,675 records were identified. Of these, 125 reviews met the criteria for inclusion. A narrative synthesis of these findings highlighted three key domains of risks associated with ADHD: mental health, physical health, social and lifestyle. Most reviews were of good and moderate quality. Discussion: This review highlights the many risks associated with having ADHD, beyond its three key symptom domains and the impact of the condition on daily functioning. Registration: International Prospective Register of Systematic Reviews (PROSPERO CRD42023404073).

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context.

BACKGROUND: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. AIMS: The aim of this study was to generate an experts' consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. METHOD: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. RESULTS: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. CONCLUSION: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial.

Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.

Waiting-list interventions for children and young people using child and adolescent mental health services: a systematic review.

QUESTION: Children and young people experience delays in assessment and/or treatment within mental health services. The objective of this systematic review, funded by the Emerging Minds Network, was to explore the current evidence base for mental health waiting list interventions to support children and young people. STUDY SELECTION AND ANALYSIS: A literature search was conducted in MEDLINE, PsycINFO, Web of Science and the Cochrane databases from 2000 to 2023 (last searched October 2023). Included studies described interventions to support children and young people and/or their family while on a waiting list for child and adolescent mental health services. Titles and abstracts were screened independently by two reviewers, data were extracted by one reviewer, confirmed by a second and a narrative synthesis was provided. FINDINGS: Eighteen studies including 1253 children and young people were identified. Studies described waiting list interventions for autism spectrum disorders, eating disorders, generic conditions, transgender health, anxiety/depression, self-harm and suicide and behavioural issues. Many interventions were multicomponent; 94% involved psychoeducation, other components included parental support, bibliotherapy and coaching. Duration of the interventions ranged from a single session to over a year; 66% involved face-to-face contact. All studies demonstrated benefits in terms of improved clinical outcomes and/or feasibility/acceptability. Evidence for service outcomes/efficiency was largely unexplored. Limitations of the underpinning research, such as sample size and low-quality papers, limit the findings. CONCLUSIONS: There is limited research exploring waiting list interventions, however, the findings from small-scale studies are promising. Further research using robust study designs and real-world implementation studies are warranted.

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.

Practitioner Review: Clinical utility of the QbTest for the assessment and diagnosis of attention-deficit/hyperactivity disorder - a systematic review and meta-analysis.

BACKGROUND: Several computerised cognitive tests (e.g. continuous performance test) have been developed to support the clinical assessment of attention-deficit/hyperactivity disorder (ADHD). Here, we appraised the evidence-base underpinning the use of one of these tests - the QbTest - in clinical practice, by conducting a systematic review and meta-analysis investigating its accuracy and clinical utility. METHODS: Based on a preregistered protocol (CRD42022377671), we searched PubMed, Medline, Ovid Embase, APA PsycINFO and Web of Science on 15th August 2022, with no language/type of document restrictions. We included studies reporting accuracy measures (e.g. sensitivity, specificity, or Area under the Receiver Operating Characteristics Curve, AUC) for QbTest in discriminating between people with and without DSM/ICD ADHD diagnosis. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A generic inverse variance meta-analysis was conducted on AUC scores. Pooled sensitivity and specificity were calculated using a random-effects bivariate model in R. RESULTS: We included 15 studies (2,058 participants; 48.6% with ADHD). QbTest Total scores showed acceptable, rather than good, sensitivity (0.78 [95% confidence interval: 0.69; 0.85]) and specificity (0.70 [0.57; 0.81]), while subscales showed low-to-moderate sensitivity (ranging from 0.48 [0.35; 0.61] to 0.65 [0.52; 0.75]) and moderate-to-good specificity (from 0.65 [0.48; 0.78] to 0.83 [0.60; 0.94]). Pooled AUC scores suggested moderate-to-acceptable discriminative ability (Q-Total: 0.72 [0.57; 0.87]; Q-Activity: 0.67 [0.58; 0.77); Q-Inattention: 0.66 [0.59; 0.72]; Q-Impulsivity: 0.59 [0.53; 0.64]). CONCLUSIONS: When used on their own, QbTest scores available to clinicians are not sufficiently accurate in discriminating between ADHD and non-ADHD clinical cases. Therefore, the QbTest should not be used as stand-alone screening or diagnostic tool, or as a triage system for accepting individuals on the waiting-list for clinical services. However, when used as an adjunct to support a full clinical assessment, QbTest can produce efficiencies in the assessment pathway and reduce the time to diagnosis.

Remote Recruitment Strategy and Structured E-Parenting Support (STEPS) App: Feasibility and Usability Study.

BACKGROUND: The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants' recruitment and the app's usability. OBJECTIVE: This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS. METHODS: myHealthE was adapted to screen patients' data. Parents' and clinicians' feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template. RESULTS: Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS' usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable. CONCLUSIONS: Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40814-021-00959-0.

Widening participation - recruitment methods in mental health randomised controlled trials: a qualitative study.

BACKGROUND: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs). METHODS: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis. RESULTS: Three focus groups and three interviews were conducted with a total N = 23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount. CONCLUSIONS: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research.

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.

Differences Between Online Trial Participants Who Have Used Statutory Mental Health Services and Those Who Have Not: Analysis of Baseline Data From 2 Pragmatic Trials of a Digital Health Intervention.

BACKGROUND: Digital health interventions (DHIs) are an established element of mental health service provision internationally. Regulators have positioned the best practice standard of evidence as an interventional study with a comparator reflective of standard care, often operationalized as a pragmatic trial. DHIs can extend health provision to those not currently using mental health services. Hence, for external validity, trials might openly recruit a mixture of people who have used mental health services and people who have not. Prior research has demonstrated phenomenological differences in mental health experience between these groups. Some differences between service users and nonservice users might influence the change created by DHIs; hence, research should systematically examine these differences to inform intervention development and evaluation work. This paper analyzes baseline data collected in the NEON (Narrative Experiences Online; ie, for people with experience of psychosis) and NEON-O (NEON for other [eg, nonpsychosis] mental health problems) trials. These were pragmatic trials of a DHI that openly recruited people who had used specialist mental health services and those who had not. All participants were experiencing mental health distress. NEON Trial participants had experienced psychosis in the previous 5 years. OBJECTIVE: This study aims to identify differences in baseline sociodemographic and clinical characteristics associated with specialist mental health service use for NEON Trial and NEON-O Trial participants. METHODS: For both trials, hypothesis testing was used to compare baseline sociodemographic and clinical characteristics of participants in the intention-to-treat sample who had used specialist mental health services and those who had not. Bonferroni correction was applied to significance thresholds to account for multiple testing. RESULTS: Significant differences in characteristics were identified in both trials. Compared with nonservice users (124/739, 16.8%), NEON Trial specialist service users (609/739, 82.4%) were more likely to be female (P<.001), older (P<.001), and White British (P<.001), with lower quality of life (P<.001) and lower health status (P=.002). There were differences in geographical distribution (P<.001), employment (P<.001; more unemployment), current mental health problems (P<.001; more psychosis and personality disorders), and recovery status (P<.001; more recovered). Current service users were more likely to be experiencing psychosis than prior service users. Compared with nonservice users (399/1023, 39%), NEON-O Trial specialist service users (614/1023, 60.02%) had differences in employment (P<.001; more unemployment) and current mental health problems (P<.001; more personality disorders), with lower quality of life (P<.001), more distress (P<.001), less hope (P<.001), less empowerment (P<.001), less meaning in life (P<.001), and lower health status (P<.001). CONCLUSIONS: Mental health service use history was associated with numerous differences in baseline characteristics. Investigators should account for service use in work to develop and evaluate interventions for populations with mixed service use histories. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04428-6.

Identifying and Categorizing Adverse Events in Trials of Digital Mental Health Interventions: Narrative Scoping Review of Trials in the International Standard Randomized Controlled Trial Number Registry.

BACKGROUND: To contextualize the benefits of an intervention, it is important that adverse events (AEs) are reported. This is potentially difficult in trials of digital mental health interventions, where delivery may be remote and the mechanisms of actions less understood. OBJECTIVE: We aimed to explore the reporting of AEs in randomized controlled trials of digital mental health interventions. METHODS: The International Standard Randomized Controlled Trial Number database was searched for trials registered before May 2022. Using advanced search filters, we identified 2546 trials in the category of mental and behavioral disorders. These trials were independently reviewed by 2 researchers against the eligibility criteria. Trials were included where digital mental health interventions for participants with a mental health disorder were evaluated through a completed randomized controlled trial (protocol and primary results publication published). Published protocols and primary results publications were then retrieved. Data were extracted independently by 3 researchers, with discussion to reach consensus when required. RESULTS: Twenty-three trials met the eligibility criteria, of which 16 (69%) included a statement on AEs within a publication, but only 6 (26%) reported AEs within their primary results publication. Seriousness was referred to by 6 trials, relatedness by 4, and expectedness by 2. More interventions delivered with human support (9/11, 82%) than those with only remote or no support (6/12, 50%) included a statement on AEs, but they did not report more AEs. Several reasons for participant dropout were identified by trials that did not report AEs, of which some were identifiable or related to AEs, including serious AEs. CONCLUSIONS: There is significant variation in the reporting of AEs in trials of digital mental health interventions. This variation may reflect limited reporting processes and difficulty recognizing AEs related to digital mental health interventions. There is a need to develop guidelines specifically for these trials to improve future reporting.

Impact of the COVID-19 pandemic on incidence of tics in children and young people: a population-based cohort study.

Background: Since the onset of the coronavirus (COVID-19) pandemic, clinicians have reported an increase in presentations of sudden and new onset tics particularly affecting teenage girls. This population-based study aimed to describe and compare the incidence of tics in children and young people in primary care before and during the COVID-19 pandemic in England. Methods: We used information from the UK Clinical Practice Research Datalink (CPRD) Aurum dataset and included males and females aged 4-11 years and 12-18 years between Jan 1, 2015, and Dec 31, 2021. We grouped the pre-pandemic period (2015-2019) and presented the pandemic years (2020, 2021) separately. We described the characteristics of children and young people with a first record of a motor or vocal tic in each time period. Incidence rates of tics by age-sex groups in 2015-2019, 2020, and 2021 were calculated. Negative binomial regression models were used to calculate incidence rate ratios. Findings: We included 3,867,709 males and females aged 4-18 years. Over 14,734,062 person-years of follow-up, 11,245 people had a first tic record during the whole study period. The characteristics of people with tics differed over time, with the proportion of females aged 12-18 years and the proportion with mental health conditions including anxiety increasing during the pandemic. Tic incidence rates per 10,000 person-years were highest for 4-11-year-old males in all three time periods (13.4 [95% confidence interval 13.0-13.8] in 2015-2019; 13.2 [12.3-14.1] in 2020; 15.1 [14.1-16.1] in 2021) but increased markedly during the pandemic in 12-18-year-old females, from 2.5 (2.3-2.7) in 2015-2019, to 10.3 (9.5-11.3) in 2020 and 13.1 (12.1-14.1) in 2021. There were smaller increases in incidence rates in 12-18-year-old males (4.6 [4.4-4.9] in 2015-2019; 4.7 [4.1-5.3] in 2020; 6.2 [5.5-6.9] in 2021) and 4-11-year-old females (4.9 [4.7-5.2] in 2015-2019; 5.7 [5.1-6.4] in 2020; 7.6 [6.9-8.3] in 2021). Incidence rate ratios comparing 2020 and 2021 with 2015-2019 were highest in the 12-18-year-old female subgroup (4.2 [3.6-4.8] in 2020; 5.3 [4.7-6.0] in 2021). Interpretation: The incidence of tics in children and young people increased across all age and sex groups during the COVID-19 pandemic, with a differentially large effect in teenage girls (a greater than four-fold increase). Furthermore, in those with tic symptoms, proportions with mental health disorders including anxiety increased during the pandemic. Further research is required on the social and contextual factors underpinning this rise in onset of tics in teenage girls. Funding: National Institute for Health Research Nottingham Biomedical Research Centre.

Understanding the Impact of Home Confinement on Children and Young People with ADHD and ASD During the COVID-19 Pandemic.

To understand whether the mental health of children and young people (CYP) with and without attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) were differentially affected by COVID-19. We analysed data (n = 6507) from the Co-Space study, a UK web-based longitudinal survey. CYP with ADHD (n = 160;2.5%), ASD (n = 465;7%), and ADHD + ASD (n = 155;2.4%) were compared with a reference group (n = 5727;88%) using parent-completed questionnaires [Strengths and Difficulties Questionnaire (SDQ) & Pandemic Anxiety Scale (PAS)]. Baseline to 1-month follow-up differences were compared using linear regression models. CYP with ADHD and/or ASD had higher scores at baseline than other CYP. At follow-up, CYP with ASD showed small but significant improvements in symptoms (SDQ), compared with the reference group. CYP with ASD experienced a worsening of disease anxiety (PAS) and CYP with ADHD a deterioration in functional impairment. These findings indicate a mixed pattern of pandemic-related impact for CYP with ADHD and/or ASD.

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.

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.

Online Parent Training for The Initial Management of ADHD referrals (OPTIMA): the protocol for a randomised controlled trial of a digital parenting intervention implemented to support parents and children on a treatment waitlist.

BACKGROUND: Children referred for attention-deficit/hyperactivity disorder (ADHD) often present with a broader pattern of conduct problems including oppositionality and defiance. This combination can be extremely stressful to parents, lower parents' self-esteem and negatively impact family life. The National Institute for Health and Care Excellence (NICE) recommends that families receive support as soon as possible after their referral. However, as clinical services are overstretched, and traditional in-person parenting intervention programmes are expensive, families often must wait times a long time prior to receiving this vital input. To address this, we have created a digital parenting programme called STEPS. It is delivered as a mobile phone app providing a set of tools and resources that can be easily accessed at parents' convenience. This study aims to evaluate the clinical and cost-effectiveness of STEPS in supporting parents of children with high levels of hyperactivity/impulsivity, inattention and conduct problems, who are waiting to be assessed by specialist children's clinical services. METHODS: Online Parent Training for The Initial Management of ADHD referrals (OPTIMA) is a two-arm superiority parallel randomised controlled trial with an internal pilot study. We aim to recruit 352 parents and their children, who have been accepted onto a waitlist in Child and Adolescent Mental Health Services or similar child health services. Parents who consent will be randomised 1:1 to either the STEPS or wait-as-usual (WAU) group. The trial will be conducted remotely (online and telephone) with measures taken at baseline and 3, 6, 9 and 12 months post-randomisation. The primary objective is to evaluate whether STEPS reduces the severity of children's oppositional and defiant behaviour, as rated by parents, measured at 3 months post-randomisation compared to WAU. DISCUSSION: Digital solutions, such as mobile phone apps, have potential for delivering psychological support for parents of children with clinical-level needs in a timely and inexpensive manner. This trial will provide data on the clinical and cost-effectiveness of the STEPS app, which could support the implementation of this scalable parenting intervention programme into standard clinical care and, ultimately, improve the outcomes for families of children referred to specialist child and adolescent health services. TRIAL REGISTRATION: ISRCTN 16523503. Prospectively registered on 18 November 2021. https://www.isrctn.com/ISRCTN16523503.

Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purkinje neurons and synaptic disorganization in the deep cerebellar nucleus (DCN). The sacsin interactome reveals that sacsin regulates interactions between cytoskeletal and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS.

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 Internet-Delivered Exposure and Response Prevention for Children and Adolescents With Tourette Syndrome: A Randomized Clinical Trial.

Importance: The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited. Objective: To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD. Design, Setting, and Participants: This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022. Interventions: Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants). Main Outcomes and Measures: The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale. Results: Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective. Conclusions and Relevance: Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost. Trial Registration: ClinicalTrials.gov identifier: NCT03916055.