Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

A personalised and systematically designed adherence intervention improves photoprotection in adults with Xeroderma Pigmentosum (XP): Results of the XPAND randomised controlled trial.

BACKGROUND: Poor adherence to photoprotection in Xeroderma Pigmentosum (XP) increases morbidity and shortens lifespan due to skin cancers. OBJECTIVE: To test a highly personalised intervention (XPAND) to reduce the dose of ultraviolet radiation (UVR) reaching the face in adults with XP, designed using known psychosocial determinants of poor photoprotection. METHODS: A two-arm parallel group randomised controlled trial, including patients with sub-optimal photoprotection to receive XPAND or a delayed intervention control arm that received XPAND the following year. XPAND comprises seven one-to-one sessions targeting photoprotection barriers (e.g., misconceptions about UVR) supported by personalised text messages, activity sheets, and educational materials incorporating behaviour change techniques. The primary outcome, mean daily UVR dose-to-face across 21 days in June-July 2018, was calculated by combining UVR exposure at the wrist with a face photoprotection activity diary. Secondary outcomes were UVR dose-to-face across 21 days in August 2018, time spent outside, photoprotective measures used outside, mood, automaticity, confidence-to-photoprotect. Financial costs and quality-adjusted life years (QALYs) were calculated. RESULTS: 16 patients were randomised, 13 provided sufficient data for primary outcome analysis. The XPAND group (n=8) had lower mean daily UVR dose-to-face [0.03 SED (SD 0.02] compared to control (n=7) [0.36 SED (SD 0.16)] (adjusted difference=-0.25, p<0.001, Hedge's g=2.2). No significant between-group differences were observed in time spent outside, photoprotection outside, mood, or confidence. The delayed intervention control showed improvements in UVR dose-to-face (adjusted difference=-0.05, Hedge's g=-0.1) , time outside (adjusted difference=-69.9, Hedge's g=-0.28), and photoprotection (adjusted difference=-0.23, Hedge's g=0.45), after receiving XPAND. XPAND was associated with lower treatment costs (£-2642; 95% CI: -£8715 to £3873) and fewer QALYs (-0.0141; 95% CI: -0.0369 to 0.0028). CONCLUSIONS: XPAND was associated with a lower UVR dose-to-face in XP patients and was cost-effective.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

A cross-sectional investigation into the role of intersectionality as a moderator of the relation between youth adversity and adolescent depression/anxiety symptoms in the community.

BACKGROUND: Adolescents exposed to adversity show higher levels of depression and anxiety, with the strongest links seen in socially/societally disadvantaged individuals (e.g., females, low socioeconomic status [SES]), as well as neurodivergent individuals. The intersection of these characteristics may be important for the differential distribution of adversity and mental health problems, though limited findings pertain to the extent to which intersectional effects moderate this association. METHODS: Combined depression/anxiety symptoms were measured using the emotional problems subscale of the Strengths and Difficulties Questionnaire in 13-14-year-olds in Cornwall, United Kingdom in 2017-2019. In a cross-sectional design (N = 11,707), multiple group structural equation modeling was used to estimate the effects of youth adversity on depression/anxiety symptoms across eight intersectionality profiles (based on gender [female/male], SES [lower/higher], and traits of hyperactivity/inattention [high/low]). Moderation effects of these characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher levels of depression/anxiety (compared to an absence of youth adversity), across intersectional profiles. This effect was moderated by gender (stronger in males; ß = 0.22 [0.11, 0.36]), and SES (stronger in higher SES; ß = 0.26 [0.14,0.40]); with indications of moderation attributable to the intersection between gender and hyperactivity/inattention (ß = 0.21 [-0.02,0.44]). CONCLUSIONS: Youth adversity is associated with heightened depression/anxiety across intersectional profiles in 13-14-year-olds. The stronger effects observed for males, and for higher SES, may be interpreted in terms of structural privilege. Preliminary findings suggest that vulnerability and resilience to the effects of youth adversity may partially depend on specific intersectional effects. Importantly, the current results invite further investigation in this emerging line of inquiry.

Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model.

BACKGROUND: There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. METHODS: A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. RESULTS: The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. CONCLUSIONS: Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

Exploring Staff Attitudes Towards Unspecified Kidney Donors in the United Kingdom: Results From the BOUnD Study.

Unspecified kidney donation (UKD) has made substantial contributions to the UK living donor programme. Nevertheless, some transplant professionals are uncomfortable with these individuals undergoing surgery. This study aimed to qualitatively explore the attitudes of UK healthcare professionals towards UKD. An opportunistic sample was recruited through the Barriers and Outcomes in Unspecified Donation (BOUnD) study covering six UK transplant centres: three high volume and three low volume centres. Interview transcripts were analysed using inductive thematic analysis. The study provided comprehensive coverage of the UK transplant community, involving 59 transplant professionals. We identified five themes: staff's conception of the ethics of UKD; presence of the known recipient in the donor-recipient dyad; need for better management of patient expectations; managing visceral reactions about the "typical" unspecified kidney donor; complex attitudes toward a promising new practice. This is the first in-depth qualitative study of attitudes of transplant professionals towards UKD. The data uncovered findings with strong clinical implications for the UKD programme, including the need for a uniform approach towards younger candidates that is adhered to by all transplant centres, the need to equally extend the rigorous assessment to both specified and unspecified donors, and a new approach to managing donor expectations.

A scoping review of trauma informed approaches in acute, crisis, emergency, and residential mental health care.

Experiences of trauma in childhood and adulthood are highly prevalent among service users accessing acute, crisis, emergency, and residential mental health services. These settings, and restraint and seclusion practices used, can be extremely traumatic, leading to a growing awareness for the need for trauma informed care (TIC). The aim of TIC is to acknowledge the prevalence and impact of trauma and create a safe environment to prevent re-traumatisation. This scoping review maps the TIC approaches delivered in these settings and reports related service user and staff experiences and attitudes, staff wellbeing, and service use outcomes.We searched seven databases (EMBASE; PsycINFO; MEDLINE; Web of Science; Social Policy and Practice; Maternity and Infant Care Database; Cochrane Library Trials Register) between 24/02/2022-10/03/2022, used backwards and forwards citation tracking, and consulted academic and lived experience experts, identifying 4244 potentially relevant studies. Thirty-one studies were included.Most studies (n = 23) were conducted in the USA and were based in acute mental health services (n = 16). We identified few trials, limiting inferences that can be drawn from the findings. The Six Core Strategies (n = 7) and the Sanctuary Model (n = 6) were the most commonly reported approaches. Rates of restraint and seclusion reportedly decreased. Some service users reported feeling trusted and cared for, while staff reported feeling empathy for service users and having a greater understanding of trauma. Staff reported needing training to deliver TIC effectively.TIC principles should be at the core of all mental health service delivery. Implementing TIC approaches may integrate best practice into mental health care, although significant time and financial resources are required to implement organisational change at scale. Most evidence is preliminary in nature, and confined to acute and residential services, with little evidence on community crisis or emergency services. Clinical and research developments should prioritise lived experience expertise in addressing these gaps.

Five-year illness trajectories across racial groups in the UK following a first episode psychosis.

PURPOSE: Psychosis disproportionally affects ethnic minority groups in high-income countries, yet evidence of disparities in outcomes following intensive early intervention service (EIS) for First Episode Psychosis (FEP) is less conclusive. We investigated 5-year clinical and social outcomes of young people with FEP from different racial groups following EIS care. METHOD: Data were analysed from the UK-wide NIHR SUPEREDEN study. The sample at baseline (n = 978) included White (n = 750), Black (n = 71), and Asian (n = 157) individuals, assessed during the 3 years of EIS, and up to 2 years post-discharge (n = 296; Black [n = 23]; Asian [n = 52] and White [n = 221]). Outcome trajectories were modelled for psychosis symptoms (positive, negative, and general), functioning, and depression, using linear mixed effect models (with random intercept and slopes), whilst controlling for social deprivation. Discharge service was also explored across racial groups, 2 years following EIS. RESULTS: Variation in linear growth over time was accounted for by racial group status for psychosis symptoms-positive (95% CI [0.679, 1.235]), negative (95% CI [0.315, 0.783]), and general (95% CI [1.961, 3.428])-as well as for functioning (95% CI [11.212, 17.677]) and depressive symptoms (95% CI [0.261, 0.648]). Social deprivation contributed to this variance. Black individuals experienced greater levels of deprivation (p < 0.001, 95% CI [0.187, 0.624]). Finally, there was a greater likelihood for Asian (OR = 3.04; 95% CI [2.050, 4.498]) and Black individuals (OR = 2.47; 95% CI [1.354, 4.520]) to remain in secondary care by follow-up. CONCLUSION: Findings suggest variations in long-term clinical and social outcomes following EIS across racial groups; social deprivation contributed to this variance. Black and Asian individuals appear to make less improvement in long-term recovery and are less likely to be discharged from mental health services. Replication is needed in large, complete data, to fully understand disparities and blind spots to care.

Real-world clinical and cost-effectiveness of community clozapine initiation: mirror cohort study.

BACKGROUND: Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear. AIMS: The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine. METHOD: This was a naturalistic study of community patients recommended for clozapine treatment. RESULTS: Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00-41.00) to 13.00 visits (IQR = 5.00-24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75-71.00) to 22.00 (IQR = 11.00-42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = -2.50, P = 0.01). Service-use costs decreased (1 year: -£963/patient (P < 0.001); 2 years: -£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: -£827.40/patient (P < 0.001); 2 year: -£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00-104.00); discharge visit 50.5 (IQR = 44.75-75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00-15.00); 2 year follow-up: 8.00 (IQR = 3.00-13.00), P = 0.023). CONCLUSIONS: These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

Interventions to improve social circumstances of people with mental health conditions: a rapid evidence synthesis.

BACKGROUND: Poor social circumstances can induce, exacerbate and prolong symptoms of mental health conditions, while having a mental health condition can also lead to worse social outcomes. Many people with mental health conditions prioritise improvement in social and functional outcomes over reduction in clinical symptoms. Interventions that improve social circumstances in this population should thus be considered a priority for research and policy. METHODS: This rapid evidence synthesis reports on randomised controlled trials of interventions to improve social circumstances across eight social domains (Housing and homelessness; money and basic needs; work and education; social isolation and connectedness; family, intimate and caring relationships; victimisation and exploitation; offending; and rights, inclusion and citizenship) in people with mental health conditions. Economic evaluations were also identified. A comprehensive, stepped search approach of the Cochrane library, MEDLINE, Embase, PsycINFO, Web of Science and Scopus was conducted. RESULTS: One systematic review and 102 randomised controlled trials were included. We did not find RCT evidence for interventions to improve family, intimate and caring relationships and only one or two trials for each of improving money and basic needs, victimisation and exploitation, and rights, inclusion and citizenship. Evidence from successful interventions in improving homelessness (Housing First) and employment (Individual Placement and Support) suggests that high-intensity interventions which focus on the desired social outcome and provide comprehensive multidisciplinary support could influence positive change in social circumstances of people with mental health conditions. Objective social isolation could be improved using a range of approaches such as supported socialisation and social skills training but interventions to reduce offending showed few benefits. Studies with cost and cost-effectiveness components were generally supportive of interventions to improve housing and vocational outcomes. More research is needed to ensure that social circumstances accompanied by high risks of further exacerbation of mental health conditions are adequately addressed. CONCLUSIONS: Although there is a large body of literature examining how to support some aspects of life for people with mental health conditions, more high-quality evidence is required in other social domains. Integration into mental health services of interventions targeting social circumstances could significantly improve a number of social outcomes.

Impact on the use and cost of other services following intervention by an inpatient pathway homelessness team in an acute mental health hospital.

BACKGROUND: Mental illness in people experiencing homelessness is common and a key reason for attendance at emergency departments and admission to hospital. AIMS: This paper describes how the KHP Pathway homeless team impacted use and cost of health and wider services. The Pathway model had never been adopted by a mental health hospital, and there had never been an economic analysis to evaluate service use before and after intervention. METHOD: Service use was measured using an adapted version of the Client Service Receipt Inventory (CSRI) with a simple before and after design at admission, 3 months and 6 months after discharge from hospital. RESULTS: During the first 3-month follow-up, over half the participants saw a GP, with an increase in the proportion seeing a psychiatrist, social worker and a mental health nurse. Attendance at emergency departments was substantially lower than at baseline. The mean total service cost was £818 at base line and £414 at 3 months. CONCLUSIONS: The adapted version of the CSRI demonstrates that patients seen by the Pathway Homelessness Team were supported to use community and scheduled health and care services. The service overcomes barriers, frequently experienced by people experiencing homelessness, in accessing support and community healthcare in the UK.

Cost of post-deployment screening for mental illness in the UK military: findings from a cluster randomised controlled trial.

BACKGROUND: Little is known about the economic impact of military mental health screening. AIMS: To investigate (a) whether post-deployment screening of military personnel affects use and cost of services and (b) the impact of psychiatric morbidity on costs. METHODS: Participants were recruited from UK Royal Marine and Army platoons and randomised to an intervention group (which received tailored advice predicated upon mental health status) or a control group (which received general advice following assessment of mental health status). The intervention costs were calculated while service use and associated costs were assessed at 12-month follow-up. RESULTS: Data were available for 6323 participants. Mean screening cost was £34. Service costs were slightly higher in the control group compared to the intervention group (£1197 vs. £1147) which was not statistically significant (bootstrapped 95%CI, -£363 to £434. In both groups, screening and control, costs were significantly higher for those who screened positive for mental health problems. CONCLUSIONS: Costs were not affected by screening. In countries that have already implemented post-deployment screening, the political cost of disinvestment needs careful consideration. Those who develop psychiatric morbidity have substantially higher care costs than those who do not.

Cost and health impacts of adherence to the National Institute for Health and Care Excellence schizophrenia guideline recommendations.

BACKGROUND: Discrepancies between the National Institute for Health and Care Excellence (NICE) schizophrenia guideline recommendations and current clinical practice in the UK have been reported. AIMS: We aim to assess whether it is cost-effective to improve adherence to the NICE schizophrenia guideline recommendations, compared with current practice. METHOD: A previously developed whole-disease model for schizophrenia, using the discrete event simulation method, was adapted to assess the cost and health impacts of adherence to the NICE recommendations. Three scenarios to improve adherence to the clinical guidelines were modelled: universal provision of cognitive-behavioural therapy for patients at clinical high risk of psychosis, universal provision of family intervention for patients with first-episode psychosis and prompt provision of clozapine for patients with treatment-resistant schizophrenia. The primary outcomes were lifetime costs and quality-adjusted life-years gained. RESULTS: The results suggest full adherence to the guideline recommendations would decrease cost and improve quality-adjusted life-years. Based on the NICE willingness-to-pay threshold of £20 000-£30 000 per quality-adjusted life-year gained, prompt provision of clozapine for patients with treatment-resistant schizophrenia results in the greatest net monetary benefit, followed by universal provision of cognitive-behavioural therapy for patients at clinical high risk of psychosis, and universal provision of family intervention for patients with first-episode psychosis. CONCLUSIONS: Our results suggest that adherence to guideline recommendations would decrease cost and improve quality-adjusted life-years. Greater investment is needed to improve guideline adherence and therefore improve patient quality of life and realise potential cost savings.

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.

Cognitive remediation therapy for patients with bipolar disorder: A randomised proof-of-concept trial.

OBJECTIVES: Cognitive remediation therapy (CRT) may benefit people with bipolar disorder type I and II for whom cognitive impairment is a major contributor to disability. Extensive research has demonstrated CRT to improve cognition and psychosocial functioning in people with different diagnoses, but randomised trials of evidenced therapy programmes are lacking for bipolar disorders. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. METHODS: This proof-of-concept, single-blind randomised trial recruited participants aged 18-65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment-as-usual (TAU) with or without individual CRT for 12 weeks. The partly computerised CRT programme ("CIRCuiTS") was therapist-led and is evidence-based from trials in those with psychotic illnesses. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention-to-treat analyses. TRIAL REGISTRATION: ISRCTN ID32290525. RESULTS: Sixty participants were recruited (02/2016-06/2018) and randomised to CRT (n = 29) or TAU (n = 31). Trial withdrawals were equivalent (CRT n = 2/29; TAU n = 5/31). CRT satisfaction indicated high acceptability. Intention-to-treat analyses (N = 60) demonstrated greater improvements for CRT- than TAU-randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in the following domains (week 25 effect sizes reported here): IQ (SES = 0.71, 95% CI [0.29,1.13]), working memory (SES = 0.70, 95% CI [0.31,1.10]), executive function (SES = 0.93, 95% CI [0.33,1.54]), psychosocial functioning (SES = 0.49, 95% CI [0.18,0.80]) and goal attainment (SES = 2.02, 95% CI [0.89,3.14]). No serious adverse events were reported. CONCLUSIONS: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof-of-concept trial encourage further investigation in a definitive trial.

The impact of manic symptoms in first-episode psychosis: Findings from the UK National EDEN study.

OBJECTIVE: The extant literature is inconsistent over whether manic symptoms in first-episode psychosis (FEP) impact on its development and trajectory. This study addressed the following: (1) Does Duration of Untreated Illness (DUI) and Duration of Untreated Psychosis (DUP) differ between FEP patients with and without manic symptoms? (2) Do manic symptoms in FEP have an impact on time to remission over 1 year? METHODS: We used data from the National EDEN study, a longitudinal cohort of patients with FEP accessing early intervention services (EIS) in England, which measured manic, positive and negative psychotic symptoms, depression and functioning at service entry and 1 year. Data from 913 patients with FEP (639 without manic symptoms, 237 with manic symptoms) were analysed using both general linear modelling and survival analysis. RESULTS: Compared to FEP patients without manic symptoms, those with manic symptoms had a significantly longer DUI, though no difference in DUP. At baseline, people with manic symptoms had higher levels of positive and negative psychotic symptoms, depression and worse functioning. At 12 months, people with manic symptoms had significantly poorer functioning and more positive psychotic symptoms. The presence of manic symptoms delayed time to remission over 1 year. There was a 19% reduced rate of remission for people with manic symptoms compared to those without. CONCLUSIONS: Manic symptoms in FEP are associated with delays to treatment. This poorer trajectory persists over 1 year. They appear to be a vulnerable and under-recognised group for poor outcome and need more focussed early intervention treatment.

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).

Emerging models and trends in mental health crisis care in England: a national investigation of crisis care systems.

BACKGROUND: Inpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day units; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature. We therefore aimed to describe the types and distribution of crisis care models across England through a national survey. METHODS: We carried out comprehensive mapping of crisis resolution teams (CRTs) using previous surveys, websites and multiple official data sources. Managers of CRTs were invited to participate as key informants who were familiar with the provision and organisation of crisis care services within their catchment area. The survey could be completed online or via telephone interview with a researcher, and elicited details about types of crisis care delivered in the local catchment area. RESULTS: We mapped a total of 200 adult CRTs and completed the survey with 184 (92%). Of the 200 mapped adult CRTs, there was a local (i.e., within the adult CRT catchment area) children and young persons CRT for 84 (42%), and an older adults CRT for 73 (37%). While all but one health region in England provided CRTs for working age adults, there was high variability regarding provision of all other community crisis service models and system configurations. Crisis cafes, street triage teams and separate crisis assessment services have all proliferated since a similar survey in 2016, while provision of acute day units has reduced. CONCLUSIONS: The composition of catchment area crisis systems varies greatly across England and popularity of models seems unrelated to strength of evidence. A group of emerging crisis care models with varying functions within service systems are increasingly prevalent: they have potential to offer greater choice and flexibility in managing crises, but an evidence base regarding impact on service user experiences and outcomes is yet to be established.

Early intervention in psychosis: health economic evaluation using the net benefit approach in a real-world setting.

BACKGROUND: Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice. AIMS: To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions. METHOD: Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18-65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment. RESULTS: From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI - €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI -€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI - €2075 to €41 931). CONCLUSIONS: Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.