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.

Use of UK faith Centre as a COVID-19 community vaccination clinic: exploring a potential model for community-based health care delivery.

INTRODUCTION: Effective and safe vaccines against COVID-19 are essential to achieve global control of the coronavirus (SARS-CoV-2). Using faith centres may offer a promising route for promoting higher vaccine uptake from certain minority ethnic groups known to be more likely to be vaccine hesitant. METHODS: This cross-sectional study explored attendees' perceptions, experiences of being offered, and receiving COVID-19 vaccination in a local mosque in Woking, Surrey, UK. About 199 attendees completed a brief questionnaire on experiences, views, motivations about attending the mosque and vaccination on site. RESULTS: The most common ethnic groups reported were White British (39.2%) and Pakistani (22.6%); 36.2% identified as Christian, 23.6% as Muslim, 5.5% as Hindu, and 17.1% had no religion. Genders was relatively equal with 90 men (45.2%) and 98 women (49.2%), and 35-44-year-olds represented the most common age group (28.1%). Views and experiences around receiving vaccinations at the mosque were predominantly positive. Primary reasons for getting vaccinated at the mosque included convenience, accessibility, positive aspects of the venue's intercultural relations, and intentions to protect oneself against COVID-19, regardless of venue type. Negative views and experiences in regards to receiving the vaccination at the mosque were less common (7% expressed no intention of recommending the centre to others), and disliked aspects mostly referred to the travel distance and long waiting times. CONCLUSIONS: Offering COVID-19 vaccination in faith centres appears acceptable for different faith groups, ensuring convenient access for communities from all religions and ethnic backgrounds.

Even low levels of tree cover improve dietary quality in West Africa.

Forests are attracting attention as a promising avenue to provide nutritious and "free" food without damaging the environment. Yet, we lack knowledge on the extent to which this holds in areas with sparse tree cover, such as in West Africa. This is largely due to the fact that existing methods are poorly designed to quantify tree cover in drylands. In this study, we estimate how various levels of tree cover across West Africa affect children's (aged 12-59 months) consumption of vitamin A-rich foods. We do so by combining detailed tree cover estimates based on PlanetScope imagery (3 m resolution) with Demographic Health Survey data from >15,000 households. We find that the probability of consuming vitamin A-rich foods increases from 0.45 to 0.53 with an increase in tree cover from the median value of 8.8 to 16.8% (which is the tree cover level at which the predicted probability of consuming vitamin A-rich foods is the highest). Moreover, we observe that the effects of tree cover vary across poverty levels and ecoregions. The poor are more likely than the non-poor to consume vitamin A-rich foods at low levels of tree cover in the lowland forest-savanna ecoregions, whereas the difference between poor and non-poor is less pronounced in the Sahel-Sudan. These results highlight the importance of trees and forests in sustainable food system transformation, even in areas with sparse tree cover.

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.

Experiences of working from home: umbrella review.

INTRODUCTION: The concept of "working from home" is extremely topical following the COVID-19 pandemic; therefore, it is unsurprising that there has been an increased interest in collating research related to homeworking. This has been carried out by multiple reviews, all with slightly different research aims and methodologies. Collating the findings from the available reviews is therefore highly beneficial to establish the experience of homeworking to create recommendations for the future of home-based work. METHODS: An umbrella review was carried out. In June 2022, literature searches were conducted across 4 electronic databases. Published reviews of literature that used a systematic process, were focused on working from home populations, and detailed factors that could be related to the personal experience of homeworking (eg, barriers, facilitators, advantages, disadvantages) were included. RESULTS: A total of 1930 records were screened and 6 review articles were included. Results report on the following sections: working environment (eg, workplace design, space conditions), personal impact (eg, satisfaction, career impact), and health (eg, physical health, well-being) including a total of 19 themes. Mixed findings were apparent for nearly all included themes, highlighting the need to consider individual and contextual circumstances when researching working from home. CONCLUSIONS: This review establishes the importance of retaining flexibility while homeworking for employees, managers, and organizations. Essentially, a one-size-fits-all approach to working from home is impractical as individual circumstances limit application. Eight recommendations for the future of working from home are suggested.

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.

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.

Fabrication of Isolated Iron Nanowires.

Nanoscale interconnects are an important component of molecular electronics. Here we use X-ray spectromicroscopy techniques as well as scanning probe methods to explore the self-assembled growth of insulated iron nanowires as a potential means of supplying an earth abundant solution. The intrinsic anisotropy of a TiO2(110) substrate directs the growth of micron length iron wires at elevated temperatures, with a strong metal-support interaction giving rise to ilmenite (FeTiO3) encapsulation. Iron nanoparticles that decorate the nanowires display magnetic properties that suggest other possible applications.

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.

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.

The relationship between homeworking during COVID-19 and both, mental health, and productivity: a systematic review.

BACKGROUND: As of March 2020, the UK public were instructed to work from home where possible and as a result, nearly half of those in employment did so during the following month. Pre-pandemic, around 5% of workers chose to work from home; it was often seen as advantageous, for example due to eliminating commuting time and increasing flexibility. However, homeworking also had negative connotations, for example, blurred boundaries between work and home life due to a sense of constant connectivity to the workplace. Understanding the psychological impact of working from home in an enforced and prolonged manner due to the COVID-19 pandemic is important. Therefore, this review sought to establish the relationship between working from home, mental health, and productivity. METHODS: In January 2022, literature searches were conducted across four electronic databases: Medline, Embase, PsycInfo and Web of Science. In February 2022 grey literature searches were conducted using Google Advanced Search, NHS Evidence; Gov.uk Publications and the British Library directory of online doctoral theses. Published and unpublished literature which collected data after March 2020, included participants who experienced working from home for at least some of their working hours, and detailed the association in terms of mental health or productivity were included. RESULTS: In total 6,906 citations were screened and 25 papers from electronic databases were included. Grey literature searching resulted in two additional papers. Therefore, 27 studies were included in this review. Findings suggest the association between homeworking and both, mental health and productivity varies considerably, suggesting a complex relationship, with many factors (e.g., demographics, occupation) having an influence on the relationship. CONCLUSION: We found that there was no clear consensus as to the association between working from home and mental health or productivity. However, there are indications that those who start homeworking for the first time during a pandemic are at risk of poor productivity, as are those who experience poor mental health. Suggestions for future research are suggested.

The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants.

Background: Fibroblast growth factor 21 (FGF21) is an essential metabolic regulator that adapts to changes in nutritional status. Severe childhood undernutrition induces elevated FGF21 levels, contributing to growth hormone (GH) resistance and subsequent linear growth attenuation potentially through a direct action on chondrocytes. Methods: In this study, we assessed expression of the components of both GH and FGF21 pathways in rare and unique human growth plates obtained from children. Moreover, we investigated the mechanistic interplay of FGF21 on GH receptor (GHR) signaling in a heterologous system. Results: Chronic FGF21 exposure increased GH-induced GHR turnover and SOCS2 expression, leading to the inhibition of STAT5 phosphorylation and IGF-1 expression. The clinical significance of FGF21 signaling through GH receptors was tested in nutritionally driven growth failure seen in very preterm (VPT) infants right after birth. VPT infants display an immediate linear growth failure after birth followed by growth catch-up. Consistent with the in vitro model data, we show that circulating FGF21 levels were elevated during deflection in linear growth compared to catch-up growth and were inversely correlated with the length velocity and circulating IGF1 levels. Conclusions: This study further supports a central role of FGF21 in GH resistance and linear growth failure and suggests a direct action on the growth plate.

Ichthyosis linked to sphingosine 1-phosphate lyase insufficiency is due to aberrant sphingolipid and calcium regulation.

Sphingosine 1-phosphate lyase (SGPL1) insufficiency (SPLIS) is a syndrome which presents with adrenal insufficiency, steroid-resistant nephrotic syndrome, hypothyroidism, neurological disease, and ichthyosis. Where a skin phenotype is reported, 94% had abnormalities such as ichthyosis, acanthosis, and hyperpigmentation. To elucidate the disease mechanism and the role SGPL1 plays in the skin barrier we established clustered regularly interspaced short palindromic repeats-Cas9 SGPL1 KO and a lentiviral-induced SGPL1 overexpression (OE) in telomerase reverse-transcriptase immortalised human keratinocytes (N/TERT-1) and thereafter organotypic skin equivalents. Loss of SGPL1 caused an accumulation of S1P, sphingosine, and ceramides, while its overexpression caused a reduction of these species. RNAseq analysis showed perturbations in sphingolipid pathway genes, particularly in SGPL1_KO, and our gene set enrichment analysis revealed polar opposite differential gene expression between SGPL1_KO and _OE in keratinocyte differentiation and Ca2+ signaling genesets. SGPL1_KO upregulated differentiation markers, while SGPL1_OE upregulated basal and proliferative markers. The advanced differentiation of SGPL1_KO was confirmed by 3D organotypic models that also presented with a thickened and retained stratum corneum and a breakdown of E-cadherin junctions. We conclude that SPLIS associated ichthyosis is a multifaceted disease caused possibly by sphingolipid imbalance and excessive S1P signaling, leading to increased differentiation and an imbalance of the lipid lamellae throughout the epidermis.

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.

Impaired protein hydroxylase activity causes replication stress and developmental abnormalities in humans.

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability. However, no germline variants in JmjC-only hydroxylases, including JMJD5, have yet been described that are associated with any human pathology. Here we demonstrate that biallelic germline JMJD5 pathogenic variants are deleterious to JMJD5 mRNA splicing, protein stability, and hydroxylase activity, resulting in a human developmental disorder characterized by severe failure to thrive, intellectual disability, and facial dysmorphism. We show that the underlying cellular phenotype is associated with increased DNA replication stress and that this is critically dependent on the protein hydroxylase activity of JMJD5. This work contributes to our growing understanding of the role and importance of protein hydroxylases in human development and disease.

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.

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.