Autopsy of a failed trial part 1: A qualitative investigation of clinician's views on and experiences of the implementation of the DAISIES trial in UK-based intensive eating disorder services.

OBJECTIVE: The DAISIES trial, comparing inpatient and stepped-care day patient treatment for adults with severe anorexia nervosa was prematurely terminated in March 2022 due to poor recruitment. This qualitative study seeks to understand the difficulties faced during the trial by investigating stakeholders' views on and experiences of its implementation. METHOD: Semi-structured interview and focus group transcripts, and trial management and oversight group meeting minutes from May 2020-June 2022 were analysed using thematic analysis. Participants were 47 clinicians and co-investigators involved with the DAISIES trial. The Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework was applied to the interpretive themes to classify barriers and facilitators to implementation. RESULTS: Five themes were identified: incompatible participation interests; changing standard practice; concerns around clinical management; systemic capacity and capability issues; and Covid-19 disrupting implementation. Applying the NASSS framework indicated the greatest implementation challenges to arise with the adopters (e.g. patients, clinicians), the organisational systems (e.g. service capacity), and the wider socio-political context (e.g. Covid-19 closing services). CONCLUSIONS: Our findings emphasise the top-down impact of systemic-level research implementation challenges. The impact of the Covid-19 pandemic accentuated pre-existing organisational barriers to trial implementation within intensive eating disorder services, further limiting the capacity for research.

Multisite randomised controlled trial of trauma-focused cognitive behaviour therapy for psychosis to reduce post-traumatic stress symptoms in people with co-morbid post-traumatic stress disorder and psychosis, compared to treatment as usual: study protocol for the STAR (Study of Trauma And Recovery) trial.

BACKGROUND: People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis. The secondary aims are to compare groups on cost-effectiveness; ascertain whether TF-CBTp impacts on a range of other meaningful outcomes; determine whether therapy effects endure; and determine acceptability of the therapy in participants and therapists. METHODS: Rater-blind, parallel arm, pragmatic randomised controlled trial comparing TF-CBTp + treatment as usual (TAU) to TAU only. Adults (N = 300) with distressing post-traumatic stress and psychosis symptoms from five mental health Trusts (60 per site) will be randomised to the two groups. Therapy will be manualised, lasting 9 months (m) with trained therapists. We will assess PTSD symptom severity (primary outcome); percentage who show loss of PTSD diagnosis and clinically significant change; psychosis symptoms; emotional well-being; substance use; suicidal ideation; psychological recovery; social functioning; health-related quality of life; service use, a total of four times: before randomisation; 4 m (mid-therapy); 9 m (end of therapy; primary end point); 24 m (15 m after end of therapy) post-randomisation. Four 3-monthly phone calls will be made between 9 m and 24 m assessment points, to collect service use over the previous 3 months. Therapy acceptability will be assessed through qualitative interviews with participants (N = 35) and therapists (N = 5-10). An internal pilot will ensure integrity of trial recruitment and outcome data, as well as therapy protocol safety and adherence. Data will be analysed following intention-to-treat principles using generalised linear mixed models and reported according to Consolidated Standards of Reporting Trials-Social and Psychological Interventions Statement. DISCUSSION: The proposed intervention has the potential to provide significant patient benefit in terms of reductions in distressing symptoms of post-traumatic stress, psychosis, and emotional problems; enable clinicians to implement trauma-focused therapy confidently in this population; and be cost-effective compared to TAU through reduced service use. TRIAL REGISTRATION: ISRCTN93382525 (03/08/20).

The impact of COVID-19 pandemic on hospital admissions for nine diseases in Iran: insight from an interrupted time series analysis.

BACKGROUND: Associations between the COVID-19 pandemic and hospitalizations have not been studied Iran. This study aimed to examine the impact of the COVID-19 pandemic on hospital admissions for nine categories of disease in seven public hospitals in Kermsnahah city, the capital of Kermsnahah province, in the west of Iran. METHODS: Data on monthly hospitalization rates (number of hospitalizations per 100,000 population) were collected for nine categories of disease for a period of 40 months (23 months before and 17 months after the COVID-19 outbreak in Iran) from the health information systems of all seven public hospitals in Kermanshah city. Categories of disease included those related to pregnancy, childbirth and the puerperium period, neoplasms, diseases of the digestive, respiratory, circulatory, genitourinary and nervous systems, mental and behavioural disorders, and infectious and parasitic diseases. Population data were extracted from the Statistics Centre of Iran. An interrupted time series analysis with segmented regression was used to examine the impact of COVID-19 on hospital admissions. FINDINGS: Average monthly hospitalization rates fell for all nine categories of disease included in the study after the onset of the pandemic, with overall rates of 85.5 per 100,000 population in the period before the COVID-19 outbreak and 50.4 per 100,000 population after the outbreak began. The relative reduction in hospitalizations for the nine diseases was 56.4%. Regression analysis of monthly data indicated a sharp decrease in hospitalisations during the first month after the COVID-19 outbreak, which was statistically significant for all diseases (p < 0.001). After the initial reduction following onset of the pandemic, significant increases were observed for some diseases, including neoplasms (increase of 3.17 per 100,000 population; p < 0.001), diseases of the digestive system (increase of 1.17 per 100,000 population; p < 0.001) and diseases related to pregnancy, childbirth and the puerperium period (increase of 1.73 per 100,000 population). For other categories of disease, rates significantly declined, including infectious and parasitic diseases (decrease of 2.46 per 100,000 population; p < 0.001). Hospitalization rates did not increase to pre-pandemic levels for any disease, with the exception of those related to pregnancy, childbirth and the puerperium period. CONCLUSIONS: Our study indicated that the COVID-19 pandemic had a significantly negative effect on hospitalizations in Iran. Although use of hospital care has gradually increased post-outbreak, it has yet to return to normal levels.

Effectiveness and cost-effectiveness of universal school-based mindfulness training compared with normal school provision in reducing risk of mental health problems and promoting well-being in adolescence: the MYRIAD cluster randomised controlled trial.

BACKGROUND: Systematic reviews suggest school-based mindfulness training (SBMT) shows promise in promoting student mental health. OBJECTIVE: The My Resilience in Adolescence (MYRIAD) Trial evaluated the effectiveness and cost-effectiveness of SBMT compared with teaching-as-usual (TAU). METHODS: MYRIAD was a parallel group, cluster-randomised controlled trial. Eighty-five eligible schools consented and were randomised 1:1 to TAU (43 schools, 4232 students) or SBMT (42 schools, 4144 students), stratified by school size, quality, type, deprivation and region. Schools and students (mean (SD); age range=12.2 (0.6); 11-14 years) were broadly UK population-representative. Forty-three schools (n=3678 pupils; 86.9%) delivering SBMT, and 41 schools (n=3572; 86.2%) delivering TAU, provided primary end-point data. SBMT comprised 10 lessons of psychoeducation and mindfulness practices. TAU comprised standard social-emotional teaching. Participant-level risk for depression, social-emotional-behavioural functioning and well-being at 1 year follow-up were the co-primary outcomes. Secondary and economic outcomes were included. FINDINGS: Analysis of 84 schools (n=8376 participants) found no evidence that SBMT was superior to TAU at 1 year. Standardised mean differences (intervention minus control) were: 0.005 (95% CI -0.05 to 0.06) for risk for depression; 0.02 (-0.02 to 0.07) for social-emotional-behavioural functioning; and 0.02 (-0.03 to 0.07) for well-being. SBMT had a high probability of cost-effectiveness (83%) at a willingness-to-pay threshold of £20 000 per quality-adjusted life year. No intervention-related adverse events were observed. CONCLUSIONS: Findings do not support the superiority of SBMT over TAU in promoting mental health in adolescence. CLINICAL IMPLICATIONS: There is need to ask what works, for whom and how, as well as considering key contextual and implementation factors. TRIAL REGISTRATION: Current controlled trials ISRCTN86619085. This research was funded by the Wellcome Trust (WT104908/Z/14/Z and WT107496/Z/15/Z).

Supporting Parents & Kids Through Lockdown Experiences (SPARKLE): A digital parenting support app implemented in an ongoing general population cohort study during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The COVID-19 related lockdowns and distancing measures have presented families with unprecedented challenges. A UK-wide cohort study tracking changes in families' mental health since early lockdown (Co-SPACE) found a significant rise in primary school-aged children's behaviour problems and associated family-related stress. Three-quarters of parents in Co-SPACE also reported wanting extra support. In SPARKLE, we will examine whether providing Co-SPACE families with a smartphone application delivering information and parenting support, Parent Positive, can reverse the negative effects of the pandemic on children and parents. The efficacy on child and parent outcomes and cost-effectiveness of Parent Positive will be examined. We will also test whether the effects are moderated by pre-existing levels of child conduct problems and usage of Parent Positive. Exploratory analyses will examine whether other baseline characteristics or lockdown circumstances moderate the effects of Parent Positive. TRIAL DESIGN: SPARKLE is a two-arm superiority parallel group randomised controlled trial embedded in an existing large UK-wide self-selected community cohort - Co-SPACE. Those who consent to SPARKLE will be randomised 1:1 to either Parent Positive or Follow-up As Usual (FAU). PARTICIPANTS: Co-SPACE (a UK-wide longitudinal cohort study) parents aged ≥18 who have children aged 4-10 years will be eligible for SPARKLE. INTERVENTION AND COMPARATOR: Parent Positive: is a digital public health intervention that can be delivered rapidly at scale to support parents in managing their children's behaviour to reduce conduct problems and levels of family conflict, which were exacerbated during the first lockdown, and which may increase further in future months as families need to cope with continuous uncertainty and further disruption to their daily lives. Co-designed with parents and based on decades of parenting research, Parent Positive consists of three elements: (i) Parenting Boosters: where advice, delivered in the form of narrated animations, videos, graphics and text is provided to help parents with eight common parenting challenges; (ii) Parenting Exchange: a facilitated parent-to-parent communication and peer support platform and; (iii) Parent Resources: giving access to carefully selected high-quality, evidence-based online parenting resources. Follow-up as Usual: FAU was selected as a comparator because the public health nature meant that an active comparator was not appropriate due to the pragmatic, rapid implementation of the trial. Individuals randomised to FAU will receive no intervention for the first two months while the data for baseline (T1), T2 and T3 are collected. They will then be given full access to the app until 30th November 2021. MAIN OUTCOMES: Outcome measures will be collected remotely through Qualtrics according to the Co-SPACE schedule at baseline (T1), which will be the Co-SPACE survey data obtained immediately prior to randomisation, and then at one month (T2) and two months (T3) post-randomisation. Measures will be collected to assess group differences in child and parent outcomes, costs and service utilisation, and adverse events. Usage of Parent Positive will also be tracked. The primary outcome is parent-reported child conduct problems at one-month post-randomisation measured using the Strengths and Difficulties Questionnaire conduct problems subscale. RANDOMISATION: Enrolled participants will be allocated to Parent Positive or FAU at the ratio of 1:1 by simple randomisation using the Randomizer function within the Qualtrics programme. Neither blocking nor stratification will be used. BLINDING (MASKING): It is not possible to blind parents enrolled in the study and Qualtrics will automatically inform parents of their group allocation. Blinded members of the research team and the senior statistician will not be given access to the Qualtrics system or the data in order to remain blinded until after the analysis is complete. We do not anticipate any serious harms associated with taking part in the intervention, therefore there will be no need to unblind any blinded staff during the study. The junior statistician will be unblinded throughout. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 616 will be recruited into the trial with 308 consenting parents randomised to each treatment arm. TRIAL STATUS: V1.0; 15.03.2021. Not yet recruiting. Anticipated start date: 1st April 2021. Anticipated end date for recruitment: 31st July 2021. TRIAL REGISTRATION: Clinicaltrial.gov: NCT04786080 . The trial was prospectively registered on 8 March 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

BACKGROUND: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4 ). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. METHODS: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. DISCUSSION: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design. TRIAL REGISTRATION: International Standard Randomised Controlled Trials ISRCTN86619085 . Registered on 3 June 2016.