Search

Objective: This article presents the benzodiazepine concentrations in urine samples from participants undergoing alcohol withdrawal in a Phase 4 "Proof of Concept" double-blind, randomized, controlled clinical trial. Chlordiazepoxide was prescribed to all participants "as needed" during the first 2 weeks only of alcohol withdrawal, to prevent serious consequences such as seizures. The trial examined effects of either mifepristone or placebo on the primary trial outcomes, which included cognitive function tests at 3 weeks and 4 weeks after the cessation of drinking. Because benzodiazepines are known to affect memory, urine benzodiazepine concentrations were measured before cognitive testing. Method: Urine samples were collected from participants immediately before each cognitive testing session, and the concentrations of unconjugated benzodiazepines (i.e., compounds active at benzodiazepine receptors) were measured by standard assay, using mass spectrometry. Results: The urine benzodiazepine measurements showed clearly that amounts of active benzodiazepine metabolites were present during the third and fourth weeks after the cessation of drinking that were as high as or higher than those seen after therapeutic dosing. Conclusions: The urinary benzodiazepine concentrations demonstrated that residual active benzodiazepine compounds can be present up to 2 weeks after the last ingestion. This could affect the results of cognitive testing in people with alcohol dependence undergoing detoxification. [ABSTRACT FROM AUTHOR]

Aim: The current research aims to systematically review the rates of adherence reported in randomised controlled clinical trials of acamprosate. It also sought to determine the reliability of the adherence monitoring and measurement methods used in these trials. Methods: The protocol for this review was pre-registered (PROSPERO: CRD42021230011). A search of the literature was conducted using OVID MEDLINE, Embase and PsycINFO from database inception to January 2021. Randomised controlled trials with a minimum sample size of 10 per treatment arm that compared the efficacy of acamprosate with placebo or other active medication in adults with a diagnosis of alcohol dependence were included. Data on rates of adherence, methods of measurement and monitoring of adherence was extracted from eligible studies independently in duplicate by two reviewers. A weighted mean adherence rate was calculated. The reliability of adherence monitoring methods was determined by calculating an adherence-assurance score based on the adherence monitoring method used. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: Fifteen studies met the eligibility criteria involving 4,450 participants (2,480 participants in the placebo arms). A mean adherence rate of 88% (54.2–95.0%) was reported across studies that reported the percentage of medication taken. A mean adherence rate of 84.9% (56.4–91.3%) was reported for trials that reported the percentage of participants taking more than 80% of medication prescribed. There is low confidence in the methods used to monitor adherence with all clinical trials having a low adherence-assurance rating. Risk of bias was judged to be high for all included studies. Conclusions: Adherence to acamprosate in clinical trials can be poor with low confidence in the methods used to measure it. Adherence rates therefore might not be accurate, which has implications for determining the efficacy of acamprosate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims The extent of variation attributable to regional differences for the efficacy of brief intervention (BI) to reduce hazardous and harmful alcohol consumption is unclear. The primary aim of this study was to determine overall efficacy of BI at 6- and 12-month follow-up in primary health care (PHC) and emergency department (ED) studies. The secondary aim was to examine whether variance in study outcome can be explained by the geographical region in which trials have taken place (European versus non-European). Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) published before August 2014 was undertaken. Twenty RCTs conducted in PHC settings with a total of 8226 participants (European = 4564/non-European = 3662) and eight RCTs conducted in ED settings with a total of 4799 participants (European = 2465/non-European = 2334) were eligible. Primary outcome measure was reduction in grams of alcohol consumed per week for BI and control groups at 6- and 12-month follow-up. An inverse variance model was applied to measure the effect of treatment in mean differences for BI and control groups at 6- and 12-month follow-up. Variance between study outcomes was explored using subgroup analysis of European versus non-European countries. Results For PHC trials at 6-month follow-up, statistically significant benefits of BI were indicated [mean difference (MD) = −21.98 g/week; 95% confidence interval (CI) = −37.40 to −6.57; P = 0.005]. At 12-month follow-up, statistically significant benefit of BI was evident (MD = −30.86 g/week; 95% CI = −46.49 to −15.23; P = 0.0001). For ED trials at 6-month follow-up, statistically significant benefits of BI were indicated (MD = −17.97 g/week; 95% CI = −29.69 to −6.24; P = 0.003). At 12-month follow-up, statistically significant benefit in favour of BI was evident (MD = −18.21 g/week; 95% CI = −26.71 to −9.70; P < 0.0001). No statistically significant differences were detected in subgroup analyses of outcomes for European versus non-European studies. Conclusions Brief intervention (BI) to reduce alcohol consumption is associated with reducing grams of alcohol consumed per week among hazardous and harmful drinkers at 6- and 12-month follow-up in primary health care and emergency department trials. The geographical region in which trials are undertaken does not appear to explain the variance in trial outcomes for reducing alcohol consumption. [ABSTRACT FROM AUTHOR]

Aims To determine the efficacy of acamprosate and naltrexone in the treatment of those who are alcohol-dependent in reducing lapse/relapse to alcohol consumption and treatment discontinuation, and to examine whether a proportion of the variance in study outcome can be explained by the country in which the trials have taken place. Method A systematic review and meta-analysis of randomized controlled trials published before September 2013 was conducted. The primary outcome measures were the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. Twenty-two randomized controlled trials (RCTs) of the efficacy of acamprosate met inclusion criteria for the meta-analysis, with a total of 2649 participants in the acamprosate group and 2587 in the placebo group. Twenty-seven RCTs of the efficacy of naltrexone met inclusion criteria for the meta-analysis, with a total of 2253 participants in the naltrexone group and 1946 in the placebo group. A random-effects model using a Mantel-Haenszel method was applied to conduct the meta-analysis. Variance in study outcomes was explored using subgroup analysis of Europe versus the rest of the world (ROW). Results The risk of returning to any drinking at 6 months was significantly lower for acamprosate [risk ratio (RR) = 0.83, 95% confidence interval (CI) = 0.78-0.89]. There was little difference in the risk of participants discontinuing treatment for any reason (RR = 0.91, 95% CI = 0.83-1.00) or due to adverse events (RR = 1.30, 95% CI = 0.96-1.75) for the acamprosate compared to placebo groups. The risk of individuals returning to any drinking at approximately 3 months was reduced significantly for the naltrexone group (RR = 0.92, 95% CI = 0.86-1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR = 0.85, 95% CI = 0.78-0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR = 0.94, 95% CI = 0.84-1.05). There was a significantly greater risk of participants in the naltrexone group discontinuing treatment due to adverse events compared to placebo (RR = 1.72, 95% CI = 1.10-2.70). Subgroup analysis by country (Europe versus ROW) revealed no difference in risk between acamprosate and placebo for the outcomes returning to any drinking at 6 months and discontinuing treatment due to adverse events. For the outcome discontinuation of treatment for any reason, there was a significant difference in RR between Europe and the ROW (χ2 = 11.65, P <0.001) for acamprosate. Acamprosate was associated with a reduction in risk of discontinuing treatment for Europe (RR = 0.86, 95% CI = 0.79-0.95), but an increase in risk of discontinuing treatment for ROW (RR = 1.23, 95% CI = 1.03-1.48). Conclusions Both acamprosate and naltrexone appear to reduce the risk of individuals returning to drinking alcohol in those who are alcohol-dependent. The country in which a randomized control trial (RCT) for the efficacy of acamprosate and naltrexone is completed does not appear to explain the variance in trial outcomes for returning to drinking alcohol or discontinuing drinking due to adverse effects. However, the country in which the RCT of acamprosate are completed may be important for explaining the variance between studies for the outcome 'discontinuing treatment for any reason'. [ABSTRACT FROM AUTHOR]

Abstract: An earlier age of onset of schizophrenia has been identified as a poor prognostic indicator. The current study examines the interaction effect of gender and cannabis use on age of onset of schizophrenia and schizoaffective disorder. This research forms part of a two-centre epidemiological study of first-episode psychosis and included individuals with a diagnosis of schizophrenia or schizoaffective disorder and an age of onset between age 16 and 45. Kaplan–Meier curves and Cox proportional hazards regression were used to compare the effects of cannabis use and gender on age of first symptom of schizophrenia. Akaike's information criteria were used to find the model with the best fit to the data. Cannabis users had an earlier age of first symptom than non-users. There was an interaction with gender; the gender difference in age of onset was diminished in cannabis smokers compared with non-cannabis smokers. The model including cannabis use interacting with gender was the most parsimonious model, followed by cannabis use alone. The addition of other illegal drug use did not improve the model. Cannabis use is associated with an earlier age of onset of schizophrenia, and the gender difference in age of onset is reduced among cannabis smokers. [Copyright &y& Elsevier]

Objective: The aim of this study was to examine the prevalence of all substance use disorders (SUD) and cannabis-specific SUDs reported in two first-episode epidemiological studies, conducted in the same catchment area, 5 years apart. Methods: The prevalence of schizophrenia in Nottingham and Aetiology and Ethnicity of Schizophrenia and Other Psychoses studies included all people with a first-episode of psychosis between 1992 and 1994 and 1997 and 1999, respectively. Those individuals with a comorbid diagnosis of a SUD (ICD-10 harmful use or dependence) were identified. Results: An upward (but not statistically significant) trend in all SUDs was found for the first-episode study population as a whole, between the two cohorts (11.9-18.2%). When analysed by age, a significant increase in cannabis-specific SUDs was observed for all first-episode cases aged 16-29 between cohorts (3.2-10.6%). When analysed by age and gender, a significant increase in all SUDs was apparent for female first-episode patients aged 16-29 between cohorts (6.1-24.2%), this same increase was not seen in male patients. Conclusions: Illegal drug misuse is common in patients with a first-episode of psychosis. However, most concerning is that when both age and gender are considered, females with a first-episode of psychosis aged 16-29 show a highly significant rise in the prevalence of all SUDs over the 1990s. More recent drug use data from England and Wales shows that the prevalence of drug use in the 21st century is declining; further epidemiological studies are required to determine whether this is also the case in young female first-episode psychosis populations. [ABSTRACT FROM AUTHOR]

Background: Alcohol dependence is a significant issue contributing to disease burden. Changes in cortisol concentrations during alcohol withdrawal are associated with cognitive deficits and symptoms of depression. Current treatments are only successful for a small proportion of people and do not target cognitive deficits and symptoms of depression experienced by those who are alcohol dependent. The aim of this research is to determine the potential efficacy of mifepristone, a type II glucocorticoid receptor antagonist, to prevent symptoms of depression and cognitive deficits following alcohol detoxification.Methods: This was a phase 2 therapeutic use trial. It was a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo treatment. The trial aimed to recruit 120 participants who met the inclusion criteria: (1) male, (2) aged 18-60 years inclusive, and (3) alcohol dependent for 5 or more years. Participants were randomised to 600 mg a day 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. Primary outcome measures were cognitive function (measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB)) and symptoms of depression (measured using the Beck Depression Inventory (BDI)) at 4 weeks post-randomisation.Results: Difficulties recruiting participants due to significant changes in the provision of inpatient care for alcohol dependence resulted in only 27 participants recruited to the trial, with data available for 21 participants. Fourteen participants were randomised to receive mifepristone and 13 to receive placebo.Conclusion: Larger trials would be needed to draw conclusions about the efficacy of mifepristone.Trial Registration: ISRCTN registry ISRCTN54001953 . Registered on 29 September 2011. [ABSTRACT FROM AUTHOR]

The author presents a discussion of "Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate" by C. Palpacuer et al. She mentions the use and effectiveness of various drugs in the treatment of alcohol abuse, the difficulties in patient compliance, and the side effect that can impact treatment.

The article presents a comment on M. A. Lewis and colleagues' study "Randomized controlled trial of a web-delivered personalized normative feedback intervention to reduce alcohol-related risky sexual behaviour among college students," which found that effects of the intervention remained significant at six-month follow-up. Topics discussed include cost-savings and effectiveness of personalized normative feedback (PNF) interventions and students' perceptions on risky sexual behaviour.

Background: There is strong evidence for the co-occurrence of mental health conditions and alcohol problems, yet physical health outcomes among this group are not well characterised. This study aimed to identify clusters of physical health conditions and their associations with mental health and problematic alcohol use in England's general population. Methods: Cross-sectional analysis of the 2014 Adult Psychiatric Morbidity Survey (N = 7546) was conducted. The survey used standardised measures of problematic alcohol use and mental health conditions, including the Alcohol Use Disorders Identification Test (AUDIT) and the Clinical Interview Schedule-Revised. Participants self-reported any lifetime physical health conditions. Latent class analysis considered 12 common physical illnesses to identify clusters of multimorbidity. Multinomial logistic regression (adjusting for age, gender, ethnicity, education, and occupational grade) was used to explore associations between mental health, hazardous drinking (AUDIT 8 +), and co-occurring physical illnesses. Results: Five clusters were identified with statistically distinct and clinically meaningful disease patterns: 'Physically Healthy' (76.62%), 'Emerging Multimorbidity' (3.12%), 'Hypertension & Arthritis' (14.28%), 'Digestive & Bowel Problems" (3.17%), and 'Complex Multimorbidity' (2.8%). Having a mental health problem was associated with increased odds of 'Digestive & Bowel Problems' (adjusted multinomial odds ratio (AMOR) = 1.58; 95% CI [1.15–2.17]) and 'Complex Multimorbidity' (AMOR = 2.02; 95% CI [1.49–2.74]). Individuals with co-occurring mental health conditions and problematic alcohol use also had higher odds of 'Digestive & Bowel Problems' (AMOR = 2.64; 95% CI [1.68–4.15]) and 'Complex Multimorbidity' (AMOR = 2.62; 95% CI [1.61–4.23]). Conclusions: Individuals with a mental health condition concurrent with problematic alcohol use experience a greater burden of physical illnesses, highlighting the need for timely treatment which is likely to include better integration of alcohol and mental health services. [ABSTRACT FROM AUTHOR]

Background: The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach. Method: AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time. Results: We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory. Conclusion: Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers. [ABSTRACT FROM AUTHOR]

Aims To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. Methods Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. Results Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. Conclusion This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Individuals diagnosed with schizophrenia are often assigned other psychiatric diagnoses during their lives. The significance of changing diagnosis has not been widely studied. Our aim was to examine the association between diagnostic change and later outcome. Individuals' diagnostic history, clinical and social outcomes were extracted from the AESOP-10 study, a 10-year follow-up of first episode psychosis cases. The association between outcome and different patterns of diagnosis over time were assessed using linear or logistic regression. Individuals always diagnosed with schizophrenia (n = 136) had worse clinical and social outcomes at follow-up than those never diagnosed with schizophrenia (n = 163), being more likely to be symptomatic, unemployed, single, and socially isolated. There was no difference in outcome between individuals always diagnosed with schizophrenia and those changing to a diagnosis of schizophrenia (n = 60), and no difference in outcome between individuals never diagnosed with schizophrenia, and those changing from a diagnosis of schizophrenia (n = 44). Individuals always and never diagnosed with schizophrenia had different outcomes. In cases of diagnostic instability participants had similar outcomes to those always assigned the diagnosis they changed to irrespective of initial diagnosis. [ABSTRACT FROM AUTHOR]

Background: To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis. Methods: AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up. Results: At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42). Conclusions: Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately. [ABSTRACT FROM AUTHOR]

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 values⩽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<0.01–0.001) and those born outside the UK (p values<0.05). Conclusions: Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes. [ABSTRACT FROM AUTHOR]

Aims To review the evidence on the effect of brief interventions (BIs) for alcohol among adults with risky alcohol consumption and comorbid mental health conditions. Methods A systematic review of randomized controlled trials (RCTs) published before May 2016 was undertaken and reported according to PRISMA guidelines. The findings were combined in a narrative synthesis. The risk of bias was assessed for included trials. Results Seventeen RCTs were included in the review and narrative synthesis: 11 in common mental health problems, and 6 in severe mental illness. There was considerable heterogeneity in study populations, BI delivery mode and intensity, outcome measures and risk of bias. Where BI was compared with a minimally active control, BI was associated with a significant reduction in alcohol consumption in four out of nine RCTs in common mental disorders and two out of five RCTs in severe mental illness. Where BI was compared with active comparator groups (such as motivational interviewing or cognitive behavioural therapy), findings were also mixed. Differences in the findings may be partly due to differences in study design, such as the intensity of BI and possibly the risk of bias. Conclusions Overall, the evidence is mixed regarding the effects of alcohol BI in participants with comorbid mental health conditions. Future well-designed research is required to answer this question more definitively. [ABSTRACT FROM AUTHOR]

Aims: To review the evidence on the effect of brief interventions (BIs) for alcohol among adults with risky alcohol consumption and comorbid mental health conditions. Methods: A systematic review of randomized controlled trials (RCTs) published before May 2016 was undertaken and reported according to PRISMA guidelines. The findings were combined in a narrative synthesis. The risk of bias was assessed for included trials. Results: Seventeen RCTs were included in the review and narrative synthesis: 11 in common mental health problems, and 6 in severe mental illness. There was considerable heterogeneity in study populations, BI delivery mode and intensity, outcome measures and risk of bias. Where BI was compared with a minimally active control, BI was associated with a significant reduction in alcohol consumption in four out of nine RCTs in common mental disorders and two out of five RCTs in severe mental illness. Where BI was compared with active comparator groups (such as motivational interviewing or cognitive behavioural therapy), findings were also mixed. Differences in the findings may be partly due to differences in study design, such as the intensity of BI and possibly the risk of bias. Conclusions: Overall, the evidence is mixed regarding the effects of alcohol BI in participants with comorbid mental health conditions. Future well-designed research is required to answer this question more definitively. [ABSTRACT FROM AUTHOR]

Objective: To compare baseline demographics and 10-year outcomes of a first-episode psychosis patient incidence cohort in order to establish whether current youth-focussed age-based criteria for early intervention services are justified by patient needs. The patients in this cohort were treated prior to the establishment of early intervention services. The study aimed to test the hypothesis that those who develop psychosis at a younger age have worse outcomes than those who develop psychosis at an older age. Methods: Data on first-episode psychosis patients from the ÆSOP-10 longitudinal follow-up study were used to compare baseline characteristics, and 10-year clinical, functional and service use outcomes between those patients who would and would not have met age-based criteria for early intervention services, in Australia or in the United Kingdom. Results: In total, 58% men and 71% women with first-episode psychosis were too old to meet current Australian-early intervention age-entry criteria (χ2 = 9.1, p = 0.003), while 21% men and 34% women were too old for UK-early intervention age-entry criteria (χ2 = 11.1, p = 0.001). The 10-year clinical and functional outcomes did not differ significantly between groups by either Australian- or UK-early intervention age-entry criteria. Service use was significantly greater among the patients young enough to meet early intervention age-criteria (Australia: incidence rate ratio = 1.35 [1.19, 1.52], p < 0.001; United Kingdom: incidence rate ratio = 1.65 [1.41, 1.93], p < 0.001). Conclusion: Current early intervention services are gender- and age-inequitable. Large numbers of patients with first-episode psychosis will not receive early intervention care under current service provision. Illness outcomes at 10-years were no worse in first-episode psychosis patients who presented within the age range for whom early intervention has been prioritised, though these patients had greater service use. These data provide a rationale to consider extension of early intervention to all, rather than just to youth. [ABSTRACT FROM AUTHOR]

A correction to the article "Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?" is presented which appeared in the previous issue of the periodical.

Objective: Primary hyperparathyroidism (PHPT) in childhood and adolescence has been considered a different disease to that seen in adults, with predominantly familial aetiology mandating open exploration to exclude parathyroid hyperplasia in contrast to the adoption of focused image-guided parathyroidectomy (FP) in adults.Study Design: A retrospective cohort study in a tertiary referral hospital setting of all children and adolescents (<18 years) undergoing parathyroid surgery for PHPT. Data were obtained from a dedicated endocrine surgery database and hospital medical records.Results: Over the 35-year study period (1980-2014), there were 31 patients who underwent parathyroidectomy for PHPT. 3 patients were from known multiple endocrine neoplasia type 1 syndrome (MEN1) families, 3 had an isolated family history of PHPT and 25 were sporadic. In the sporadic group, 24 (96%) presented with symptomatic hypercalcaemia, affecting the gastrointestinal, musculoskeletal, genitourinary or neuropsychiatric systems. In the 25 patients with sporadic PHPT, nine (36%) had FP with a single adenoma removed with a 100% initial cure rate. Sixteen patients (64%) in the sporadic group had an open exploration: 14 had single gland disease while 2 patients required a second procedure to achieve a final cure rate of 100%. Of the three patients with MEN1, one was cured, one has persistent hyperparathyroidism after FP and the third has permanent hypoparathyroidism after open exploration.Conclusions: The majority of children and adolescents with PHPT have symptomatic disease due to a single adenoma. They can therefore be managed in a similar fashion to their adult counterparts with preoperative localisation studies aiming to permit FP in a day case setting. [ABSTRACT FROM AUTHOR]

Background: Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls. Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among 'high-risk' drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions. Design and methods: The study design comprises two linked randomised controlled trials to evaluate the effectiveness and cost-effectiveness of two intervention strategies compared with screening alone. One trial will focus on high-risk adolescent drinkers attending Emergency Departments (Eds) and the other will focus on those identified as low-risk drinkers or abstinent from alcohol but attending the same ED. Our primary (null) hypothesis is similar for both trials: Personalised Feedback and Brief Advice (PFBA) and Personalised Feedback plus electronic Brief Intervention (eBI) are no more effective than screening alone in alcohol consumed at 12 months after randomisation as measured by the Time-Line Follow-Back 28-day version. Our secondary (null) hypothesis relating to economics states that PFBA and eBI are no more cost-effective than screening alone. In total 1,500 participants will be recruited into the trials, 750 high-risk drinkers and 750 low-risk drinkers or abstainers. Participants will be randomised with equal probability, stratified by centre, to either a screening only control group or one of the two interventions: single session of PFBA or eBI. All participants will be eligible to receive treatment as usual in addition to any trial intervention. Individual participants will be followed up at 6 and 12 months after randomisation. (Continued on next page) (Continued from previous page) Discussion: The protocol represents an ambitious innovative programme of work addressing alcohol use in the adolescent population. Trial registration: ISRCTN45300218. Registered 5th July 2014. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption and related harm increase rapidly from the age of 12 years. We evaluated whether alcohol screening and brief intervention is effective and cost-effective in delaying hazardous or harmful drinking amongst low-risk or abstaining adolescents attending Emergency Departments (EDs).Methods: This ten-centre, three-arm, parallel-group, single-blind, pragmatic, individually randomised trial screened ED attenders aged between 14 and 17 years for alcohol consumption. We sampled at random one third of those scoring at most 2 on AUDIT-C who had access to the internet and, if aged under 16, were Gillick competent or had informed consent from parent or guardian. We randomised them between: screening only (control intervention); one session of face-to-face Personalised Feedback and Brief Advice (PFBA); and PFBA plus an electronic brief intervention (eBI) on smartphone or web. We conducted follow-up after six and 12 months. The principal outcomes were alcohol consumed over the 3 months before 12-month follow up, measured by AUDIT-C; and quality-adjusted life-years.Findings: Between October 2014 and May 2015, we approached 5,016 eligible patients of whom 3,326 consented to be screened and participate in the trial; 2,571 of these were low-risk drinkers or abstainers, consuming an average 0.14 units per week. We randomised: 304 to screening only; 285 to PFBA; and 294 to PFBA and eBI. We found no significant difference between groups, notably in weekly alcohol consumption: those receiving screening only drank 0.10 units (95% confidence interval 0.05 to 0.18); PFBA 0.12 (0.06 to 0.21); PFBA and eBI 0.10 (0.05 to 0.19).Interpretation: While drinking levels remained low in this population, this trial found no evidence that PFBA with or without eBI was more effective than screening alone in reducing or delaying alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls. Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among 'high-risk' drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions.Design and Methods: The study design comprises two linked randomised controlled trials to evaluate the effectiveness and cost-effectiveness of two intervention strategies compared with screening alone. One trial will focus on high-risk adolescent drinkers attending Emergency Departments (Eds) and the other will focus on those identified as low-risk drinkers or abstinent from alcohol but attending the same ED. Our primary (null) hypothesis is similar for both trials: Personalised Feedback and Brief Advice (PFBA) and Personalised Feedback plus electronic Brief Intervention (eBI) are no more effective than screening alone in alcohol consumed at 12 months after randomisation as measured by the Time-Line Follow-Back 28-day version. Our secondary (null) hypothesis relating to economics states that PFBA and eBI are no more cost-effective than screening alone. In total 1,500 participants will be recruited into the trials, 750 high-risk drinkers and 750 low-risk drinkers or abstainers. Participants will be randomised with equal probability, stratified by centre, to either a screening only control group or one of the two interventions: single session of PFBA or eBI. All participants will be eligible to receive treatment as usual in addition to any trial intervention. Individual participants will be followed up at 6 and 12 months after randomisation.Discussion: The protocol represents an ambitious innovative programme of work addressing alcohol use in the adolescent population.Trial Registration: ISRCTN45300218. Registered 5th July 2014. [ABSTRACT FROM AUTHOR]