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Background: Given the degenerative nature of the condition, people living with motor neuron disease (MND) experience high levels of psychological distress. The purpose of this research was to investigate the cost-effectiveness of acceptance and commitment therapy (ACT), adapted for the specific needs of this population, for improving quality of life., Methods: A trial-based cost-utility analysis over a 9-month period was conducted comparing ACT plus usual care (n = 97) versus usual care alone (n = 94) from the perspective of the National Health Service. In the primary analysis, quality-adjusted life years (QALYs) were computed using health utilities generated from the EQ-5D-5L questionnaire. Sensitivity analyses and subgroup analyses were also carried out., Results: Difference in costs was statistically significant between the two arms, driven mainly by the intervention costs. Effects measured by EQ-5D-5L were not statistically significantly different between the two arms. The incremental cost-effectiveness was above the £20,000 to £30,000 per QALY gained threshold used in the UK. However, the difference in effects was statistically significant when measured by the McGill Quality of Life-Revised (MQOL-R) questionnaire. The intervention was cost-effective in a subgroup experiencing medium deterioration in motor neuron symptoms., Conclusions: Despite the intervention being cost-ineffective in the primary analysis, the significant difference in the effects measured by MQOL-R, the low costs of the intervention, the results in the subgroup analysis, and the fact that ACT was shown to improve the quality of life for people living with MND, suggest that ACT could be incorporated into MND clinical services., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease., Methods: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391)., Findings: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention., Interpretation: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services., Funding: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association., Competing Interests: Declaration of interests RLG, CJM, BJT, CVR, MBu, MBr, PK, EJT, DAW, MAS, CDG, LMM, LHG, AA-C, TY, VL, CC, PJS, and RJH declare institutional financial support from the grant for the submitted work (National Institute for Health and Care Research Health Technology Assessment 16/81/01). RLG, MAS, RJH, MBr, CC, TY, PJS, CJM, AA-C, VL, and LHG are supported by a public research body (National Institute for Health and Care Research Biomedical Research Centres). LHG has received royalties for books on psychology and neuropsychology and fees for lectures on neurology. AA-C and PJS receive payment for consultancy and advisory board participation from commercial organisations (Amylyx, Apellis, Biogen, Brainstorm, Clene Therapeutics, Cytokinetics, GenieUs, GSK, Lilly, Mitsubishi Tanabe Pharma, Novartis, OrionPharma, Quralis, Sano, Sanofi, and Wave Pharmaceuticals), none of which are related to the content of this submitted work. RWO, LMM, and CF have received grants for research from public bodies. RWO has received grants for research and trials from commercial organisations (Amylyx Pharmaceuticals, Biogen, Orphazyme) and received payment for neurological medicolegal work. RWO and CF sit on safety monitoring or advisory boards for motor neuron disease. RWO, JE, and AH sit on boards in organisations associated with motor neuron disease. AH receives grant funding for his clinical role at Motor Neurone Disease Association. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs., Objectives: We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research., Design: We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines., Setting: NHS hospitals, with primary data collection at four sites., Participants: Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions., Interventions: Prophylaxis for all patients, none and according to selected risk assessment models., Main Outcome Measures: Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models., Results: We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%., Limitations: Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias., Conclusions: Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research., Future Work: Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation., Study Registration: This study is registered as PROSPERO CRD42020165778 and Researchregistry5216., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment ; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

Introduction: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS., Methods and Analysis: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs., Ethics and Dissemination: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences., Trial Registration Number: ISRCTN88667898., Competing Interests: Competing interests: GB, JP, KEMD, RG, KH, DPap, ER, CB, MG, OC, CC, GG, MK, CK, RN, DPal, AP, NS, ES, TdS, AV, SW, BS report no relevant competing interests. AC reports no relevant disclosures since 2017. RH reports attendance at paid advisory boards with Novartis, Biogen and Roche. CAY reports personal compensation for serving on scientific advisory boards, conference support or speaker honoraria from BMS, Biogen, Celgene, Cytokinetics, GW Pharmaceuticals, Novartis, Roche and Teva. Pharmaceuticals. PAM reports grants from National Institute of Health Research, non-financial support from National Institute of Health Research, grants from Benaroya Research Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health, during the conduct of the study; personal fees from Jasper Therapeutics, personal fees from Magenta Therapeutics, personal fees from Rubius Therapeutics, outside the submitted work. JAS declares consultancy for Jazz, Medac, Vertex and Kiadis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Social skills interventions are commonly recommended to help children and young people with autism spectrum disorder develop social skills, but some struggle to engage in these interventions. LEGO ® (LEGO System A/S, Billund, Denmark) based therapy, a group social skills intervention, aims to be more interesting and engaging., Objective: To evaluate the clinical effectiveness of LEGO ® based therapy on the social and emotional skills of children and young people with autism spectrum disorder in school settings compared with usual support. Secondary objectives included evaluations of cost-effectiveness, acceptability and treatment fidelity., Design: A cluster randomised controlled trial randomly allocating participating schools to either LEGO ® based therapy and usual support or usual support only., Setting: Mainstream schools in the north of England., Participants: Children and young people (aged 7-15 years) with autism spectrum disorder, their parent/guardian, an associated teacher/teaching assistant and a facilitator teacher/teaching assistant (intervention schools only)., Intervention: Schools randomised to the intervention arm delivered 12 weekly sessions of LEGO ® based therapy, which promotes collaborative play and encourages social problem-solving in groups of three children and young people with a facilitator (trained teacher or teaching assistant). Participants received usual support from school and community services. Participants in the control arm received usual support only. Research assistants and statisticians were blind to treatment allocation., Main Outcome Measure: The social skills subscale of the Social Skills Improvement System (SSIS), completed by the children and young people's unblinded teacher pre randomisation and 20 weeks post randomisation. The SSIS social skills subscale measures social skills including social communication, co-operation, empathy, assertion, responsibility and self-control. Participants completed a number of other pre- and post-randomisation measures of emotional health, quality of life, loneliness, problem behaviours, academic competence, service resource utilisation and adverse events., Results: A total of 250 children and young people from 98 schools were randomised: 127 to the intervention arm and 123 to the control arm. Intention-to-treat analysis of the main outcome measure showed a modest positive difference of 3.74 points (95% confidence interval -0.16 to 7.63 points, standardised effect size 0.18; p  = 0.06) in favour of the intervention arm. Statistical significance increased in per-protocol analysis, with a modest positive difference (standardised effect size 0.21; p  = 0.036). Cost-effectiveness of the intervention was found in reduced service use costs and a small increase in quality-adjusted life-years. Intervention fidelity and acceptability were positive. No intervention-related adverse events or effects were reported., Conclusions: The primary and pre-planned sensitivity analysis of the primary outcome consistently showed a positive clinical difference, with modest standardised effect sizes of between 0.15 and 0.21. There were positive health economics and qualitative findings, corroborated by the difference between arms for the majority of secondary outcomes, which were not statistically significant but favoured the intervention arm. Post hoc additional analysis was exploratory and was not used in drawing this conclusion. Given the small positive change, LEGO ® based therapy for children and young people with autism spectrum disorder in schools should be considered., Limitations: The primary outcome measure was completed by an unblinded teacher (rather than by the facilitator)., Future Work: The study team recommends future research into LEGO ® based therapy, particularly in school environments., Trial Registration: This trial is registered as ISRCTN64852382., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/49/32) and is published in full in Public Health Research ; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.

Background: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND., Methods: PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months., Results: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status., Conclusions: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway., Trial Registration: The study was pre-registered with the ISRCTN Registry (ISRCTN12655391)., (© 2023. The Author(s).)

Lay Abstract: Autism is characterised by keen interests and differences in social interactions and communication. Activities that help autistic children and young people with social skills are commonly used in UK schools. LEGO ® based therapy is a new activity that provides interesting and fun social opportunities for children and young people and involves building LEGO ® models together. This study looked at LEGO ® based therapy for the social skills of autistic children and young people in schools. It was a randomised controlled trial, meaning each school was randomly chosen (like flipping a coin) to either run LEGO ® based therapy groups in school over 12 weeks and have usual support from school or other professionals, or only have usual support from school or other professionals. The effect of the LEGO ® based therapy groups was measured by asking children and young people, their parents/guardians, and a teacher at school in both arms of the study to complete some questionnaires. The main objective was to see if the teacher's questionnaire answers about the children and young people's social skills changed between their first and second completions. The social skills of participants in the LEGO ® based therapy groups were found to have improved in a small way when compared to usual support only. The study also found that LEGO ® based therapy was not very costly for schools to run and parents/guardians and teachers said they thought it was good for their children and young people. We suggest further research into different potential benefits of LEGO ® based therapy.

Objectives: We evaluated the accuracy of using routine health service data to identify hospital-acquired thrombosis (HAT) and major bleeding events (MBE) compared with a reference standard of case note review., Design: A multicentre observational cohort study., Setting: Four acute hospitals in the UK., Participants: A consecutive unselective cohort of general medical and surgical patients requiring hospitalisation for a period of >24 hours during the calendar year 2021. We excluded paediatric, obstetric and critical care patients due to differential risk profiles., Interventions: We compared preidentified sources of routinely collected information (using hospital coding data and local contractually mandated thrombosis datasets) to data extracted from case notes using a predesigned workflow methodology., Primary and Secondary Outcome Measures: We defined HAT as objectively confirmed venous thromboembolism occurring during hospital stay or within 90 days of discharge and MBE as per international consensus., Results: We were able to source all necessary routinely collected outcome data for 87% of 2008 case episodes reviewed. The sensitivity of hospital coding data (International Classification of Diseases 10th Revision, ICD-10) for the diagnosis of HAT and MBE was 62% (95% CI, 54 to 69) and 38% (95% CI, 27 to 50), respectively. Sensitivity improved to 81% (95% CI, 75 to 87) when using local thrombosis data sets., Conclusions: Using routinely collected data appeared to miss a substantial proportion of outcome events, when compared with case note review. Our study suggests that currently available routine data collection methods in the UK are inadequate to support efficient study designs in venous thromboembolism research., Trial Registration Number: NIHR127454., Competing Interests: Competing interests: During the completion of this study, SG, DH, CR, BJH, MBu and MB received funding from the National Institute of Health Research (NIHR) for academic work in this area, through competitive grant application and CR was appointed to an NIHR doctoral research fellow position. Following the completion of this study, CR has been subsequently employed by Pfizer limited. Pfizer did not fund nor support this study and was not involved in drafting or revising this manuscript., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Haemorrhoids are common and can significantly impact the personal and working lives of individuals. Those with more severe symptoms and those not responding to conservative management may require surgery. Current surgical techniques are associated with a degree of postoperative discomfort which may delay return to normal activity. Recurrence is lower in more radical procedures but resulting pain is higher. Radiofrequency ablation (RFA) is a new technique that is gaining popularity and has several hypothesised benefits, including reduced pain and recurrence. However, available evidence is limited. A recent overview from the National Institute for Health and Clinical Excellence recommended more research, in the form of randomised controlled trials, be carried out before further investment is made by national health services. Our aim is to assess whether RFA is at least as good in terms of recurrence as existing surgical interventions, but superior in terms of pain, for patients with symptomatic grade II and III haemorrhoids., Methods: The RadiO fRequency ablatION for haemorrhoids (ORION) trial will be a pragmatic multicentre patient/assessor-blind parallel group-controlled trial with economic evaluation. The target sample size is 376 participants (188 per arm) and is based on two co-primary endpoints: (i) a non-inferiority design for recurrence and (ii) superiority design for pain at seven days. Participants with grade II or III haemorrhoids will be recruited in 16 National Health Service hospitals and randomised (1:1) to either RFA or surgeon's choice of surgery., Conclusions: Results will inform future practice for the treatment of grade II-III haemorrhoids and provide evidence for national health services on future investments in RFA., Trial Registration: ISRCTN14474552., (© 2022. The Author(s).)

Background: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health., Aims: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND., Methods: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling., Discussion: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND., Trial Registration: ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017, https://www.isrctn.com/ISRCTN12655391 ., Protocol Version: 3.1 (10/06/2020)., (© 2022. The Author(s).)

Background: Evidence for parenting programs to improve wellbeing in children under three is inconclusive. We investigated the fidelity, impact, and cost-effectiveness of two parenting programs delivered within a longitudinal proportionate delivery model ('E-SEE Steps')., Methods: Eligible parents with a child ≤ 8 weeks were recruited into a parallel two-arm, assessor blinded, randomized controlled, community-based, trial with embedded economic and process evaluations. Post-baseline randomization applied a 5:1 (intervention-to-control) ratio, stratified by primary (child social-emotional wellbeing (ASQ:SE-2)) and key secondary (maternal depression (PHQ-9)) outcome scores, sex, and site. All intervention parents received the Incredible Years® Baby Book (IY-B), and were offered the targeted Infant (IY-I)/Toddler (IY-T) program if eligible, based on ASQ:SE-2/PHQ-9 scores. Control families received usual services. Fidelity data were analysed descriptively. Primary analysis applied intention to treat. Effectiveness analysis fitted a marginal model to outcome scores. Cost-effectiveness analysis involved Incremental Cost-Effectiveness Ratios (ICERs)., Results: The target sample (N = 606) was not achieved; 341 mothers were randomized (285:56), 322 (94%) were retained to study end. Of those eligible for the IY-I (n = 101), and IY-T (n = 101) programs, 51 and 21 respectively, attended. Eight (of 14) groups met the 80% self-reported fidelity criteria. No significant differences between arms were found for adjusted mean difference scores; ASQ:SE-2 (3.02, 95% CI: -0.03, 6.08, p = 0.052), PHQ-9 (-0.61; 95% CI: -1.34, 0.12, p = 0.1). E-SEE Steps had higher costs, but improved mothers' Health-related Quality of Life (0.031 Quality Adjusted Life Year (QALY) gain), ICER of £20,062 per QALY compared to control. Serious adverse events (n = 86) were unrelated to the intervention., Conclusions: E-SEE Steps was not effective, but was borderline cost-effective. The model was delivered with varying fidelity, with lower-than-expected IY-T uptake. Changes to delivery systems and the individual programs may be needed prior to future evaluation., Trial Registration: International Standard Randomized Controlled Trial Number: ISRCTN11079129., Competing Interests: All authors were supported by the grant, National Institute for Health Research (NIHR) Public Health Research (PHR) (ref 13/93/10). TB, SB, KP and GR were also supported by the NIHR Yorkshire and Humber Applied Research Collaboration (ARC-YH; Ref: NIHR200166, see https://www.arc-yh.nihr.ac.uk,); VB by the South West Peninsula ARC (PenARC, Ref: NIHR200167, see https://arc-swp.nihr.ac.uk). Public Health England supported research sites’ excess treatment costs (no award number). This above funding does not alter our adherence to PLOS ONE policies on sharing data and materials. In addition, TB is a voluntary Trustee for Children’s Early Intervention Trust (CEIT). Early Intervention Wales Training (EIWT) is owned by CEIT and offers training courses, including Incredible Years® (IY). Trustees do not benefit financially from trainings or CEIT/EIWT activities. ESEE study trainings were arranged via the IY developer in the U.S., not via EIWT.

Objectives: To assess the cost-effectiveness of LEGO-based therapy compared with usual support., Design: Cost-utility analysis alongside randomised control trial., Setting: Mainstream primary and secondary schools in the UK., Participants: 248 children and young people (CYP) with autism spectrum disorder (ASD) aged 7-15 years., Intervention: LEGO-based therapy is a group social skills intervention designed specifically for CYP with ASD. Through play, CYP learn to use the skills such as joint attention, sharing, communication and group problem-solving. CYP randomised to the intervention arm received 12 weekly sessions of LEGO-based therapy and usual support, while CYP allocated to control arm received usual support only., Main Outcome Measures: Average costs based on National Health Service (NHS) and personal social services perspective and quality-adjusted life years (QALYs) measured by EQ-5D-Y over time horizon of 1 year were collected during the trial. Incremental cost-effectiveness ratio (ICER) was calculated, and non-parametric bootstrapping was conducted. The uncertainty around the ICER estimates was presented using cost-effectiveness acceptability curve (CEAC). A set of sensitivity analyses were conducted to assess the robustness of the primary findings., Results: After adjustment and bootstrapping, on average, CYP in LEGO-based therapy group incurred less costs (incremental cost was -£251 (95% CI -£752 to £268)) and gained marginal improvement in QALYs (QALYs gained 0.009 (95% CI -0.008 to 0.028)). The CEAC shows that the probability of LEGO-based therapy being cost-effective was 94% at the willingness-to-pay threshold of £20 000 per QALY gained. Results of sensitivity analyses were consistent with the primary outcomes., Conclusion: Compared with usual support, LEGO-based therapy produced marginal reduction in costs and improvement in QALYs. Results from both primary and sensitivity analyses suggested that LEGO-based therapy was likely to be cost-effective., Trial Registration Number: ISRCTN64852382., Competing Interests: Competing interests: The research team was aware that the LEGO name is a registered trademark and followed the fair use policy in regard to the LEGO brand throughout the duration of the trial. GGdlC co-authored the LEGO-based therapy manual, which formed the basis of the intervention delivered in the trial. The co-authors of the manual have given us full permission to use the manual without license and to develop an abridged version. They have also stated their support for us in writing our own version and will become co-authors on any future publications. GGdlC has also agreed for the team to adapt the fidelity checklist used in her previous study. GGdlC is a Director of Play included a community interest company that offers training and resources for interventions involving play bricks for children. We have provisional agreement with Jessica Kingsley Publishers who have expressed interest in publishing the abridged manual. However, we are not tied to them as a publisher. There are no other financial and/or competing interests to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Many eye movement desensitization and reprocessing (EMDR) therapists moved their practice online during COVID-19. We conducted surveys and interviews to understand the implementation and acceptability of online EMDR therapy. From 17 June to 2nd August 2021 an online survey was open to EMDR therapists from the EMDR Association UK & Ireland and EMDR International Association email lists, and, through them, their clients. Questions related to determinants of implementation (for therapists) and acceptability (for clients) of online EMDR. Semi-structured interviews were conducted with a sample of therapist respondents to provide a deeper understanding of survey responses. Survey responses were received from therapists (n = 562) from five continents, and their clients (n = 148). 88% of clients responded as being extremely or very comfortable receiving EMDR therapy online. At the initial point of 'social distancing', 54% of therapists indicated strong or partial reluctance to deliver online EMDR therapy compared to 11% just over one year later. Four fifths of therapists intended to continue offering online therapy after restrictions were lifted. Free-text responses and interview data showed that deprivation and clinical severity could lead to exclusion from online EMDR. Internet connectivity could disrupt sessions, lead to cancellations, or affect the therapy process. Therapists benefited from training in online working. Online EMDR is generally acceptable to therapists and clients, with reservations about digital exclusion, case severity, poor internet connectivity and the need for training. Further research is needed to confirm that online EMDR is clinically non-inferior to in-person working., Supplementary Information: The online version contains supplementary material available at 10.1007/s40737-022-00260-0., Competing Interests: Conflict of interestMBrayne receives fees for providing EMDR psychotherapy, supervision and training and is a committee member of the EMDR Association UK's East Anglia Regional Group. For MBursnall, BT, HB, ES and DH, their institution was reimbursed by the EMDR Association East Anglia Regional Group for this work., (© The Author(s) 2022.)

Background: The WHO and National Institute for Health and Care Excellence recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to compare the accuracy of triage tools for predicting severe illness in adults presenting to the ED with suspected COVID-19., Methods: We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the UK. We collected data from people attending with suspected COVID-19 and used presenting data to determine the results of assessment with the WHO algorithm, National Early Warning Score version 2 (NEWS2), CURB-65, CRB-65, Pandemic Modified Early Warning Score (PMEWS) and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome., Results: We analysed data from 20 891 adults, of whom 4611 (22.1%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2553 (12.2%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point rule) 0.70; SFAHP (7-point rule) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support. At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.97 and 0.95, respectively) at the expense of specificity (0.30 and 0.27, respectively). The NEWS2 score showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used., Conclusion: CURB-65, PMEWS and the NEWS2 score provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity., Trial Registration Number: ISRCTN56149622., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice., Methods: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice., Results: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms., Conclusion: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com)., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Dorsal cheilectomy of the first metatarsophalangeal joint is an accepted treatment to alleviate dorsal impingement, pain, and reduced dorsiflexion in hallux rigidus. Traditionally performed via an open incision, this procedure has more recently been performed using minimally invasive techniques despite limited supportive published evidence., Methods: From December 2012 through December 2017, a retrospective analysis of all cheilectomies performed in our institution was done. The surgical technique was recorded along with any subsequent procedures performed for either persistent or recurrent pain, and complications were also noted. A comparison between open and minimally invasive outcomes was performed. In total, 171 cheilectomies were performed during this period. There were 38 open and 133 minimally invasive procedures., Results: At a mean 3-year follow-up, the reoperation rates of the 2 groups were different with only 1 (2.6%) of the open group requiring a fusion, while 17 (12.8%) of the minimally invasive surgical (MIS) group required further surgery (relative risk, 4.86; P = .059). In the open group, there was 1 (2.6%) complication, compared with 15 (11.3%) in the minimally invasive group (relative risk, 4.29; P = .076)., Conclusion: While patients may opt for MIS cheilectomy with a proposed faster recovery time and better cosmesis, they should be counseled about the risks and benefits of both methods, and that the technique of MIS cheilectomy utilized in this study appears to have an increased relative risk of requiring a further procedure., Level of Evidence: Level III, retrospective comparative series.