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Background and aims: Alcohol use increases throughout adolescence. Emergency department (ED) attendance is an opportunity for alcohol screening and brief intervention (ASBI), which is effective for adults. This trial evaluated the effectiveness and cost-effectiveness of ASBI compared with screening alone (SA) in high-risk adolescents. Design, Setting and Participants: Multi-centre, three-group, single-blind, individually randomized trial with follow-ups after 6 and 12 months in 10 ED settings in England. From October 2014 to May 2015 we screened 3327 adolescents aged 14 to 18 years, of whom 756 (22.7%) scored at least 3 on the Alcohol Use Disorders Identification Test: consumption (AUDIT-C) and consented to participate in this trial. Mean age was 16.1 years; 50.2% were female and 84.9% were white. Interventions: Interventions were personalized feedback and brief advice (PFBA), personalized feedback plus electronic brief intervention (eBI) and SA. Measures: The primary outcome was the weekly alcohol consumed in standard UK units (8 g ethanol) at 12 months post-randomization, derived from extended AUDIT-C. Economic outcomes included quality of life and service use, from perspectives of both the National Health Service and personal social services (NHS&PSS) and society. Findings: At 12 months, mean weekly consumption was 2.99 [95% confidence interval (CI) = 2.38–3.70] standard units for the SA group, 3.56 (95% CI = 2.90, 4.32) for PFBA and 3.18 (95% CI = 2.50, 3.97) for eBI, showing no significant differences. The PFBA group consumed mean 0.57 (−0.36, 1.70) units more than SA; and eBIs consumed 0.19 (−0.71, 1.30) more. Bayes factors suggested lack of effectiveness explained non-significance. From the NHS&PSS perspective, economic analysis showed that PFBA and eBI were not cost-effective compared with SA: PFBA yielded incremental cost-effectiveness ratio of £6213 (−£736 843, £812 884), with the intervention having 54% probability of being cost-effective compared with SA at the £20 000 WTP threshold. Conclusions: In emergency departments in England, neither personalized feedback and brief advice nor personalized feedback plus electronic brief intervention showed evidence of being effective or cost-effective when compared with screening alone in reducing alcohol consumption among adolescents. We thank the participating EDs: St Thomas’ Hospital; King's College Hospital; Ealing Hospital; Croydon University Hospital; Hull Royal Infirmary; Darlington Memorial Hospital; Queen Elizabeth Hospital, Gateshead; North Tees Hospital, Hartlepool; South Tyneside District Hospital, South Shields; and Sunderland Royal Hospital; and all the researchers who successfully delivered the trial in these EDs. We thank the Trial Steering Committee and our software developers at Codeface Ltd for developing the trial management app. and the eBI app. SIPS City. This is a summary of independent research funded by a National Institute for Health Research (NIHR) Programme Grant for Applied Research (RP-PG-0609-10162). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. C.D., P.D. and J.S. were supported by the NIHR Specialist Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. C.D. and P.D. were also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care at King's College Hospital NHS Foundation Trust and the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. T.P. was funded by a NIHR Clinical Doctoral Research Fellowship and the NIHR Yorkshire and the Humber Clinical Research Network.

© Cambridge University Press 2018Â This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. © Cambridge University Press 2018. Background Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.Methods We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.Results Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p valuesâ 0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t =-2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t =-2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values

Background. A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change.Method. Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests.Results. Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder anddrug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis. Conclusions. Diagnoses other than schizophrenia should to be regarded as potentially provisional.

BackgroundThe incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.AimTo investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.MethodÆSOP-10 is a ten-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.ResultsThere was evidence that, compared with white British, black Caribbean patients experienced worse clinical, social, and service use outcomes, and black African patients experienced worse social and service use outcomes. There was evidence that baseline social disadvantage contributed to these disparities.ConclusionThese findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.

Background: Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol. Methods/Design: The study is a Phase 4 therapeutic use, "Proof of Concept" trial. The trial is a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo. The trial aims to recruit 120 participants referred for an inpatient alcohol detoxification from community alcohol teams, who meet the inclusion criteria; 1) Male, 2) Aged 18-60 inclusive, 3) alcohol dependent for 5 or more years. A screening appointment will take place prior to admission to inpatient alcohol treatment units to ensure that the individual is suitable for inclusion in the trial in accordance with the inclusion and exclusion criteria. On admission participants are randomised to receive 600 mg a day of mifepristone (200 mg morning, afternoon and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Participants will remain in the trial for 4 weeks (at least 2 weeks as an inpatient) and will be followed up at 3, 6 and 12 months post randomisation. Primary outcome measures are cognitive function at week 3 and 4 after cessation of drinking and symptoms of depression over the 4 weeks after cession of drinking, measured using the Cambridge Neuropsychological Test Automated battery and Beck Depression Inventory, respectively. Secondary outcome measures are severity of the acute phase of alcohol withdrawal, alcohol craving, symptoms of protracted withdrawal and maintenance of abstinence and levels of relapse drinking at follow-up. Discussion: The current trial will provide evidence concerning the role of glucocorticoid Type II receptor activation in cognitive function and depression during acute alcohol withdrawal and the efficacy of treatment with mifepristone. Trial registration: ISRCTN: ISRCTN54001953 , Registered 29th September 2011.

Background Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol. Methods/Design The study is a Phase 4 therapeutic use, “Proof of Concept” trial. The trial is a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo. The trial aims to recruit 120 participants referred for an inpatient alcohol detoxification from community alcohol teams, who meet the inclusion criteria; 1) Male, 2) Aged 18–60 inclusive, 3) alcohol dependent for 5 or more years. A screening appointment will take place prior to admission to inpatient alcohol treatment units to ensure that the individual is suitable for inclusion in the trial in accordance with the inclusion and exclusion criteria. On admission participants are randomised to receive 600 mg a day of mifepristone (200 mg morning, afternoon and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Participants will remain in the trial for 4 weeks (at least 2 weeks as an inpatient) and will be followed up at 3, 6 and 12 months post randomisation. Primary outcome measures are cognitive function at week 3 and 4 after cessation of drinking and symptoms of depression over the 4 weeks after cession of drinking, measured using the Cambridge Neuropsychological Test Automated battery and Beck Depression Inventory, respectively. Secondary outcome measures are severity of the acute phase of alcohol withdrawal, alcohol craving, symptoms of protracted withdrawal and maintenance of abstinence and levels of relapse drinking at follow-up. Discussion The current trial will provide evidence concerning the role of glucocorticoid Type II receptor activation in cognitive function and depression during acute alcohol withdrawal and the efficacy of treatment with mifepristone. Trial registration ISRCTN: ISRCTN54001953, Registered 29th September 2011.

BackgroundThe incidence of psychotic disorders is elevated in some minority ethnic populations. However, we know little about the outcome of psychoses in these populations.AimTo investigate patterns and determinants of long-term course and outcome of psychoses by ethnic group following a first episode.MethodÆSOP-10 is a ten-year follow-up of an ethnically diverse cohort of 532 individuals with first-episode psychosis identified in the UK. Information was collected, at baseline, on clinical presentation and neurodevelopmental and social factors and, at follow-up, on course and outcome.ResultsThere was evidence that, compared with white British, black Caribbean patients experienced worse clinical, social, and service use outcomes, and black African patients experienced worse social and service use outcomes.There was evidence that baseline social disadvantage contributed to these disparities.ConclusionThese findings suggest ethnic disparities in the incidence of psychoses extend, for some groups, to worse outcomes in multiple domains.