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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]

BackgroundElectronic screening and brief intervention (eSBI) has been shown to reduce alcohol consumption, but its effectiveness over time has not been subject to meta-analysis. ObjectiveThe current study aims to conduct a systematic review and meta-analysis of the available literature to determine the effectiveness of eSBI over time in nontreatment-seeking hazardous/harmful drinkers. MethodsA systematic review and meta-analysis of relevant studies identified through searching the electronic databases PsychINFO, Medline, and EMBASE in May 2013. Two members of the study team independently screened studies for inclusion criteria and extracted data. Studies reporting data that could be transformed into grams of ethanol per week were included in the meta-analysis. The mean difference in grams of ethanol per week between eSBI and control groups was weighted using the random-effects method based on the inverse-variance approach to control for differences in sample size between studies. ResultsThere was a statistically significant mean difference in grams of ethanol consumed per week between those receiving an eSBI versus controls at up to 3 months (mean difference –32.74, 95% CI –56.80 to –8.68, z=2.67, P=.01), 3 to less than 6 months (mean difference –17.33, 95% CI –31.82 to –2.84, z=2.34, P=.02), and from 6 months to less than 12 months follow-up (mean difference –14.91, 95% CI –25.56 to –4.26, z=2.74, P=.01). No statistically significant difference was found at a follow-up period of 12 months or greater (mean difference –7.46, 95% CI –25.34 to 10.43, z=0.82, P=.41). ConclusionsA significant reduction in weekly alcohol consumption between intervention and control conditions was demonstrated between 3 months and less than 12 months follow-up indicating eSBI is an effective intervention.

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]

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]

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]

Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches. [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.

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]

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.

A list of referees for articles submitted to the scholarly journal "Addiction" in 2020 is presented, including scholars Max Abbott, Eshan Adeli, and Mir Ali.