Olanzapine for young PEople with aNorexia nervosa (OPEN): A protocol for an open-label feasibility study.

INTRODUCTION: Antipsychotics are routinely prescribed off-label for anorexia nervosa (AN) despite limited evidence. This article presents a protocol of a study aiming to assess the feasibility of a future definitive trial on olanzapine in young people with AN. METHODS AND ANALYSIS: In an open-label, one-armed feasibility study, 55 patients with AN or atypical AN, aged 12-24, receiving outpatient, inpatient or day-care treatment who are considered for olanzapine treatment will be recruited from NHS sites based in England. Assessments will be conducted at screening, baseline and at 8-, 16 weeks, 6- and 12 months. Primary feasibility parameters will be proportions of patients who agree to take olanzapine and who adhere to treatment and complete study assessments. Qualitative methods will be used to explore acceptability of the intervention and study design. Secondary feasibility parameters will be changes in body mass index, psychopathology, side effects, health-related quality of life, carer burden and proportion of participants who would enrol in a future randomised controlled trial. The study is funded by the National Institute for Health Research via Health Technology Assessment programme. DISCUSSION: Olanzapine for young PEople with aNorexia nervosa will inform a future randomised controlled trial on the efficacy and safety of prescribing olanzapine in young people with AN.

Autopsy of a failed trial part 2: Outcomes, challenges, and lessons learnt from the DAISIES trial.

OBJECTIVE: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure. METHOD: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis. RESULTS: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38). CONCLUSIONS: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies.

Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study.

BACKGROUND: Research has shown that 20-30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders. AIMS: To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD. METHOD: We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16-25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression. RESULTS: In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI -2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm. CONCLUSIONS: ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.

Implementation of the trial emulation approach in medical research: a scoping review.

BACKGROUND: When conducting randomised controlled trials is impractical, an alternative is to carry out an observational study. However, making valid causal inferences from observational data is challenging because of the risk of several statistical biases. In 2016 Hernán and Robins put forward the 'target trial framework' as a guide to best design and analyse observational studies whilst preventing the most common biases. This framework consists of (1) clearly defining a causal question about an intervention, (2) specifying the protocol of the hypothetical trial, and (3) explaining how the observational data will be used to emulate it. METHODS: The aim of this scoping review was to identify and review all explicit attempts of trial emulation studies across all medical fields. Embase, Medline and Web of Science were searched for trial emulation studies published in English from database inception to February 25, 2021. The following information was extracted from studies that were deemed eligible for review: the subject area, the type of observational data that they leveraged, and the statistical methods they used to address the following biases: (A) confounding bias, (B) immortal time bias, and (C) selection bias. RESULTS: The search resulted in 617 studies, 38 of which we deemed eligible for review. Of those 38 studies, most focused on cardiology, infectious diseases or oncology and the majority used electronic health records/electronic medical records data and cohort studies data. Different statistical methods were used to address confounding at baseline and selection bias, predominantly conditioning on the confounders (N = 18/49, 37%) and inverse probability of censoring weighting (N = 7/20, 35%) respectively. Different approaches were used to address immortal time bias, assigning individuals to treatment strategies at start of follow-up based on their data available at that specific time (N = 21, 55%), using the sequential trial emulations approach (N = 11, 29%) or the cloning approach (N = 6, 16%). CONCLUSION: Different methods can be leveraged to address (A) confounding bias, (B) immortal time bias, and (C) selection bias. When working with observational data, and if possible, the 'target trial' framework should be used as it provides a structured conceptual approach to observational research.

Past-year intimate partner violence perpetration among people with and without depression: an individual participant data (IPD) meta-mediation analysis.

PURPOSE: To investigate whether (1) depression is associated with increased risk of past-year intimate partner violence (IPV) perpetration, disaggregated by sex, after controlling for potential confounders; (2) observed associations are mediated by alcohol misuse or past-year IPV victimisation. METHODS: Systematic review and individual participant data (IPD) meta-mediation analysis of general population surveys of participants aged 16 years or older, that were conducted in a high-income country setting, and measured mental disorder and IPV perpetration in the last 12 months. RESULTS: Four datasets contributed to meta-mediation analyses, with a combined sample of 12,679 participants. Depression was associated with a 7.4% and 4.8% proportion increase of past-year physical IPV perpetration among women and men, respectively. We found no evidence of mediation by alcohol misuse. Among women, past-year IPV victimisation mediated 45% of the total effect of depression on past-year IPV perpetration. Past-year severe IPV victimisation mediated 60% of the total effect of depression on past-year severe IPV perpetration. We could not investigate IPV victimisation as a mediator among men due to perfect prediction. CONCLUSIONS: Mental health services, criminal justice services, and domestic violence perpetrator programmes should be aware that depression is associated with increased risk of IPV perpetration. Interventions to reduce IPV victimisation might help prevent IPV perpetration by women. Data collection on mental disorder and IPV perpetration should be strengthened in future population-based surveys, with greater consistency of data collection across surveys, as only four studies were able to contribute to the meta-mediation analysis.

Moderators of treatment effect in a randomised controlled trial of single- and multi-family therapy for anorexia nervosa in adolescents and emerging adults.

INTRODUCTION: Multi-family therapy for anorexia nervosa (MFT-AN) is a novel, group-based intervention that intensifies single-family therapy for anorexia nervosa (FT-AN), with the aim of improving outcomes. The current study explored treatment moderators in a randomised controlled trial (N = 167) of FT-AN and MFT-AN for young people (adolescents/emerging adults aged 13-20 years) with anorexia nervosa. METHODS: Data were analysed using multiple linear regression. Six hypothesised baseline participant and parent factors were tested as possible moderators of treatment effect on end-of-treatment and follow-up percentage of median Body Mass Index (%mBMI); age, eating disorder symptom severity, perceived family conflict (young person and parent ratings) and parent-rated experiences of caregiving (positive and negative). RESULTS: Greater parent-rated positive caregiving experiences moderated treatment outcomes at follow-up (ß = -0.47, 95%CI: -0.91, -0.03, p = 0.04), but not end-of-treatment. Participants who had fewer parent-rated positive caregiving experiences at baseline had higher weight at follow-up if they had MFT-AN compared to FT-AN. No other hypothesised baseline factors moderated treatment outcome (p's > 0.05). DISCUSSION: The current study suggests MFT-AN may be indicated for families who present with fewer positive caregiving experiences to treatment. The MFT-AN group context may help to promote mentalisation and hope for these families, which may be harder to achieve in single-family treatment. Future research is needed to empirically evaluate how and why MFT-AN supports this group more. TRIAL REGISTRATION: ISRCTN registry: ISRCTN11275465, registered 29 January 2007.

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.

Variations in the uptake of telemental health technologies in community and crisis mental health services during the early pandemic: a survey of mental health professionals in the UK.

BACKGROUND: One of the many challenges faced by mental health services during the COVID-19 pandemic was how to deliver care during lockdown. In community and crisis services, this often meant rapidly adopting or expanding the use of telemental health technologies, including phone and video calls. The aim of this study is to explore variations in use and report staff views of such technologies during the early stages of the pandemic. The primary analysis compared rates of use between professions, demographic groups, genders, regions, and crisis and community services. METHODS: We used data from an online survey conducted by the Mental Health Policy Research Unit in Spring 2020 regarding the impact of the pandemic on mental healthcare in the United Kingdom. We included quantitative data from all professional groups working in community or crisis services providing care to working age adults, including general and specialist services. Our outcome of interest was the percentage of clients whom clinicians primarily interacted with via videocall. We also collected demographics and professional characteristics such as the type of mental health service respondents worked in. In addition, we explored respondents' views and experiences of telemental health as a medium for providing care. RESULTS: 978 participants were included in the primary analysis (834 provided outcome data for community services, 193 for crisis services). In community services, virtually all staff reported stopping some or all face-to-face appointments following the onset of the pandemic, with a large majority using video or phone call appointments where possible instead. Telemental health use was higher in community than in crisis services, and amongst professionals who mainly provided psychotherapy or peer support than in other groups. There was also evidence of use being lower in regions in Northern England, Scotland, and Wales than elsewhere. There was no evidence of an association with staff gender, age, or ethnicity. Staff were generally positive about telemental health and intended to make more use of technologies following the pandemic. However, significant barriers to its use were also reported, often involving skills and available infrastructure. CONCLUSIONS: Despite its rapid implementation, telemental health was viewed positively by clinicians who saw it as an effective alternative to face-to-face appointments in some contexts, including during the pandemic. However, adoption of the technology also has the potential to exacerbate existing or create new inequalities without effective management of training and infrastructure needs.

Pandemic-related emergency psychiatric presentations for self-harm of children and adolescents in 10 countries (PREP-kids): a retrospective international cohort study.

To examine the differences in hospital emergency psychiatric presentations for self-harm of children and adolescents during the covid-19 lockdown in March and April 2020 compared with the same period in 2019. Retrospective cohort study. We used electronic patient records from 23 hospital emergency departments in ten countries grouped into 14 areas. We examined data on 2073 acute hospital presentations by 1795 unique children and adolescents through age 18. We examined the total number of emergency psychiatric hospital presentations and the proportion of children and adolescents presenting with severe self-harm as our two main outcome measures. In addition, we examined sociodemographic and clinical characteristics and clinical management variables for those presenting with self-harm. To compare the number of hospital presentations between 2020 and 2019 a negative binomial model was used. For other variables, individual participant data (IPD) meta-analyses were carried out. Emergency psychiatric hospital presentations decreased from 1239 in 2019 to 834 in 2020, incident rate ratio 0.67, 95% CI 0.62-0.73; p < 0.001. The proportion of children and adolescents presenting with self-harm increased from 50% in 2019 to 57% in 2020, odds ratio 1.33, 1.07-1.64; p = 0.009 but there was no difference in the proportion presenting with severe self-harm. Within the subpopulation presenting with self-harm the proportion of children and adolescents presenting with emotional disorders increased from 58 to 66%, odds ratio 1.58, 1.06-2.36; p = 0.025. The proportion of children and adolescents admitted to an observation ward also decreased from 13 to 9% in 2020, odds ratio 0.52, 0.28-0.96; p = 0.036. Service planners should consider that, during a lockdown, there are likely to be fewer emergency psychiatric presentations. Many children and adolescents with psychiatric emergencies might not receive any service. A focus on developing intensive community care services with outreach capabilities should be prioritised.

Psychological and demographic characteristics of 368 patients with dissociative seizures: data from the CODES cohort.

BACKGROUND: We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology. METHODS: Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic). RESULTS: Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men. CONCLUSIONS: Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.

Cost effectiveness of therapist delivered cognitive behavioural therapy and web-based self-management in irritable bowel syndrome: the ACTIB randomised trial.

BACKGROUND: Telephone therapist delivered CBT (TCBT) and web-based CBT (WCBT) have been shown to be significantly more clinically effective than treatment as usual (TAU) at reducing IBS symptom severity and impact at 12 months in adults with refractory IBS. In this paper we assess the cost-effectiveness of the interventions. METHODS: Participants were recruited from 74 general practices and three gastroenterology centres in England. Interventions costs were calculated, and other service use and lost employment measured and costed for one-year post randomisation. Quality-adjusted life years (QALYs) were combined with costs to determine cost-effectiveness of TCBT and WCBT compared to TAU. RESULTS: TCBT cost £956 more than TAU (95% CI, £601-£1435) and generated 0.0429 more QALYs. WCBT cost £224 more than TAU (95% CI, - £11 to £448) and produced 0.029 more QALYs. Compared to TAU, TCBT had an incremental cost per QALY of £22,284 while the figure for WCBT was £7724. After multiple imputation these ratios increased to £27,436 and £17,388 respectively. Including lost employment and informal care, TCBT had costs that were on average £866 lower than TAU (95% CI, - £1133 to £2957), and WCBT had costs that were £1028 lower than TAU (95% CI, - £448 to £2580). CONCLUSIONS: TCBT and WCBT resulted in more QALYs and higher costs than TAU. Complete case analysis suggests both therapies are cost-effective from a healthcare perspective. Imputation for missing data reduces cost-effectiveness but WCTB remained cost-effective. If the reduced societal costs are included both interventions are likely to be more cost-effective. Trial registration ISRCTN44427879 (registered 18.11.13).

ADVANCE integrated group intervention to address both substance use and intimate partner abuse perpetration by men in substance use treatment: a feasibility randomised controlled trial.

BACKGROUND: Substance use is a risk factor for intimate partner abuse (IPA) perpetration. Delivering perpetrator interventions concurrently with substance use treatment shows promise. METHODS: The feasibility of conducting an efficacy and cost-effectiveness trial of the ADVANCE 16-week intervention to reduce IPA by men in substance use treatment was explored. A multicentre, parallel group individually randomised controlled feasibility trial and formative evaluation was conducted. Over three temporal cycles, 104 men who had perpetrated IPA towards a female (ex) partner in the past year were randomly allocated to receive the ADVANCE intervention + substance use treatment as usual (TAU) (n = 54) or TAU only (n = 50) and assessed 16-weeks post-randomisation. Participants' (ex) partners were offered support and 27 provided outcome data. Thirty-one staff and 12 men who attended the intervention participated in focus groups or interviews that were analysed using the framework approach. Pre-specified criteria assessed the feasibility of progression to a definitive trial: 1) ≥ 60% of eligible male participants recruited; 2) intervention acceptable to staff and male participants; 3) ≥ 70% of participants followed-up and 4) levels of substance use and 5) IPA perpetrated by men in the intervention arm did not increase from average baseline level at 16-weeks post-randomisation. RESULTS: 70.7% (104/147) of eligible men were recruited. The formative evaluation confirmed the intervention's acceptability. Therapeutic alliance and session satisfaction were rated highly. The overall median rate of intervention session attendance (of 14 compulsory sessions) was 28.6% (range 14.3-64.3% by the third cycle). 49.0% (51/104) of men and 63.0% (17/27) of their (ex) partners were followed-up 16-weeks post-randomisation. This increased to 100% of men and women by cycle three. At follow-up, neither substance use nor IPA perpetration had worsened for men in the intervention arm. CONCLUSIONS: It was feasible to deliver the ADVANCE intervention in substance use treatment services, although it proved difficult to collect data from female (ex)partners. While some progression criteria were met, others were not, although improvements were demonstrated by the third cycle. Lessons learned will be implemented into the study design for a definitive trial of the ADVANCE intervention. TRIAL REGISTRATION: ISRCTN79435190 prospectively registered 22nd May 2018.

Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff.

PURPOSE: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. METHODS: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities, and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. RESULTS: 2,180 staff from a range of sectors, professions, and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. CONCLUSION: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.

Exploring mechanisms of action in clinical trials of complex surgical interventions using mediation analysis.

BACKGROUND: Surgical interventions allow for tailoring of treatment to individual patients and implementation may vary with surgeon and healthcare provider. In addition, in clinical trials assessing two competing surgical interventions, the treatments may be accompanied by co-interventions. AIMS: This study explores the use of causal mediation analysis to (1) delineate the treatment effect that results directly from the surgical intervention under study and the indirect effect acting through a co-intervention and (2) to evaluate the benefit of the surgical intervention if either everybody in the trial population received the co-intervention or nobody received it. METHODS: Within a counterfactual framework, relevant direct and indirect effects of a surgical intervention are estimated and adjusted for confounding via parametric regression models, for the situation where both mediator and outcome are binary, with baseline stratification factors included as fixed effects and surgeons as random intercepts. The causal difference in probability of a successful outcome (estimand of interest) is calculated using Monte Carlo simulation with bootstrapping for confidence intervals. Packages for estimation within standard statistical software are reviewed briefly. A step by step application of methods is illustrated using the Amaze randomised trial of ablation as an adjunct to cardiac surgery in patients with irregular heart rhythm, with a co-intervention (removal of the left atrial appendage) administered to a subset of participants at the surgeon's discretion. The primary outcome was return to normal heart rhythm at one year post surgery. RESULTS: In Amaze, 17% (95% confidence interval: 6%, 28%) more patients in the active arm had a successful outcome, but there was a large difference between active and control arms in the proportion of patients who received the co-intervention (55% and 30%, respectively). Causal mediation analysis suggested that around 1% of the treatment effect was attributable to the co-intervention (16% natural direct effect). The controlled direct effect ranged from 18% (6%, 30%) if the co-intervention were mandated, to 14% (2%, 25%) if it were prohibited. Including age as a moderator of the mediation effects showed that the natural direct effect of ablation appeared to decrease with age. CONCLUSIONS: Causal mediation analysis is a useful quantitative tool to explore mediating effects of co-interventions in surgical trials. In Amaze, investigators could be reassured that the effect of the active treatment, not explainable by differential use of the co-intervention, was significant across analyses.

Correction to: Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

BMC family practice integrated GP care for patients with persistent physical symptoms: feasibility cluster randomised trial.

BACKGROUND: Patients continue to suffer from medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS). General practitioners (GPs) play a key role in the management of PPS and require further training. Patients are often frustrated with the care they receive. This study aims to assess the acceptability of an 'integrated GP care' approach which consists of offering self-help materials to patients with PPS and offering their GPs training on how to utilise cognitive behavioural skills within their consultations, as well as assessing the feasibility of conducting a future trial in primary care to evaluate its benefit. METHODS: A feasibility cluster randomised controlled trial was conducted in primary care, South London, UK. GP practices (clusters) were randomly allocated to 'integrated GP care plus treatment as usual' or 'treatment as usual'. Patients with PPS were recruited from participating GP practices before randomisation. Feasibility parameters, process variables and potential outcome measures were collected at pre-randomisation and at 12- and 24-weeks post-randomisation at cluster and individual participant level. RESULTS: Two thousand nine hundred seventy-eight patients were identified from 18 GP practices. Out of the 424 patients who responded with interest in the study, 164 fully met the eligibility criteria. One hundred sixty-one patients provided baseline data before cluster randomisation and therefore were able to participate in the study. Most feasibility parameters indicated that the intervention was acceptable and a future trial feasible. 50 GPs from 8 GP practices (randomised to intervention) attended the offer of training and provided positive feedback. Scores in GP knowledge and confidence increased post-training. Follow-up rate of patients at 24 weeks was 87%. However estimated effect sizes on potential clinical outcomes were small. CONCLUSIONS: It was feasible to identify and recruit patients with PPS. Retention rates of participants up to 24 weeks were high. A wide range of health services were used. The intervention was relatively low cost and low risk. This complex intervention should be further developed to improve patients'/GPs' utilisation of audio/visual and training resources before proceeding to a full trial evaluation. TRIAL REGISTRATION: NCT02444520  (ClinicalTrials.gov).

Correction to: Integrated GP care for patients with persistent physical symptoms: feasibility cluster randomised trial.

An amendment to this paper has been published and can be accessed via the original article.

Patients' Experiences of Telephone-Based and Web-Based Cognitive Behavioral Therapy for Irritable Bowel Syndrome: Longitudinal Qualitative Study.

BACKGROUND: Cognitive behavioral therapy (CBT) is recommended in guidelines for people with refractory irritable bowel syndrome (IBS). However, the availability of CBT is limited, and poor adherence has been reported in face-to-face CBT. OBJECTIVE: Nested within a randomized controlled trial of telephone- and web-delivered CBT for refractory IBS, this qualitative study aims to identify barriers to and facilitators of engagement over time with the interventions, identify social and psychological processes of change, and provide insight into trial results. METHODS: A longitudinal qualitative study was nested in a randomized controlled trial. Repeated semistructured interviews were conducted at 3 (n=34) and 12 months (n=25) post baseline. Participants received telephone-based CBT (TCBT; n=17 at 3 months and n=13 at 12 months) or web-based CBT (WCBT; n=17 at 3 months and n=12 at 12 months). Inductive thematic analysis was used to analyze the data. RESULTS: Participants viewed CBT as credible for IBS, perceived their therapists as knowledgeable and supportive, and liked the flexibility of web-based and telephone-based delivery; these factors facilitated engagement. Potential barriers to engagement in both groups (mostly overcome by our participants) included initial skepticism and concerns about the biopsychosocial nature of CBT, initial concerns about telephone-delivered talking therapy, challenges of maintaining motivation and self-discipline given already busy lives, and finding nothing new in the WCBT (WCBT group only). Participants described helpful changes in their understanding of IBS, attitudes toward IBS, ability to recognize IBS patterns, and IBS-related behaviors. Consistent with the trial results, participants described lasting positive effects on their symptoms, work, and social lives. Reasons and remedies for some attenuation of effects were identified. CONCLUSIONS: Both TCBT and WCBT for IBS were positively received and had lasting positive impacts on participants' understanding of IBS, IBS-related behaviors, symptoms, and quality of life. These forms of CBT may broaden access to CBT for IBS.

Assessing telephone-delivered cognitive-behavioural therapy (CBT) and web-delivered CBT versus treatment as usual in irritable bowel syndrome (ACTIB): a multicentre randomised trial.

OBJECTIVE: To evaluate the clinical effectiveness of two modes of cognitive-behavioural therapy (CBT) for IBS compared with treatment as usual (TAU) in refractory IBS. DESIGN: A three-arm randomised controlled trial assessing telephone-delivered CBT (TCBT), web-based CBT (WCBT) with minimal therapist support, and TAU. Blinding participants and therapists was not possible. Chief investigator, assessors and statisticians were blinded. Participants were adults with refractory IBS (clinically significant symptoms for ≥12 months despite first-line therapies), recruited by letter and opportunistically from 74 general practices and three gastroenterology centres in London and South of England between May 2014 to March 2016. Co-primary outcomes were IBS Symptom Severity Score (IBS-SSS) and Work and Social Adjustment Scale (WSAS) at 12 months. RESULTS: 558/1452 (38.4%) patients screened for eligibility were randomised: 76% female: 91% white: mean age 43 years. (391/558) 70.1% completed 12 months of follow-up. Primary outcomes: Compared with TAU (IBS-SSS 205.6 at 12 months), IBS-SSS was 61.6 (95% CI 33.8 to 89.5) points lower (p<0.001) in TCBT and 35.2 (95% CI 12.6 to 57.8) points lower (p=0.002) in WCBT at 12 months. Compared with TAU (WSAS score 10.8 at 12 months) WSAS was 3.5 (95% CI 1.9 to 5.1) points lower (p<0.001) in TCBT and 3.0 (95% CI 1.3 to 4.6) points lower (p=0.001) in WCBT. All secondary outcomes showed significantly greater improvement (p≤0.002) in CBT arms compared with TAU. There were no serious adverse reactions to treatment. CONCLUSION: Both CBT interventions were superior to TAU up to 12 months of follow-up. TRIAL REGISTRATION NUMBER: ISRCTN44427879.

Characteristics of 698 patients with dissociative seizures: A UK multicenter study.

OBJECTIVE: We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. METHODS: We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non-Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. RESULTS: In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self-reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two-thirds were unemployed. SIGNIFICANCE: Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.