Background: the HemiSPAIRE trial is being conducted to determine whether a modified
muscle sparing technique (SPAIRE - “Save Piriformis and Internus, Repairing Externus”) in
hip hemiarthroplasty brings clinical benefits compared to the standard lateral technique in
adults aged 60 years or older, with a displaced intracapsular hip fracture. This article describes
the detailed statistical analysis plan for the trial.
Methods and design: HemiSPAIRE is a definitive, pragmatic, superiority, multicentre,
randomised controlled trial (with internal pilot) with two parallel groups. Participants, ward
staff and all research staff involved in post-operative assessments are blinded to allocation.
This article describes in detail (1) the primary and secondary outcomes, (2) the statistical
analysis principles, including: a survivor average causal effect (SACE) method chosen
specifically to address the issue of potential bias from differential survival between trial arms,
which was seen from data review by the Trial Steering Committee; the participants that will be
included in each analysis; the covariates that will be included in each analysis, and how the
results will be presented, (3) planned main analysis of the primary outcome; (4) planned
analyses of the secondary outcomes, (5) planned additional analyses of the primary and
secondary outcomes.

Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task, of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: in a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

Social anxiety disorder (SAD) has been related to alcohol use disorder (AUD). Shyness can be considered a subclinical analogue of SAD, yet there is little research into the effect of alcohol on anxiety levels in highly-shy individuals. This naturalistic study investigated acute and sub-acute effects of alcohol in high and low shy social drinkers. 97 individuals were tested at home and assigned to either consume alcohol to normal levels (n = 50) or to remain sober (n = 47). Baseline measures of AUD symptoms, shyness and social phobia were taken. Measures of state anxiety were taken at baseline, following a period of alcohol consumption or sobriety, and the following morning. Marginally decreased acute anxiety resulting from alcohol consumption in high shyness was observed. A significant increase in anxiety the day following drinking was observed in highly-shy participants. There was a significant correlation between anxiety elevation on the second day and AUDIT scores in highly-shy participants. This study suggests anxiety during hangover is linked to AUD symptoms in highly-shy individuals, providing a potential marker for increased AUD risk, which could inform prevention and treatment.

AbstractThere is clear experimental evidence for a causal link between alcohol misuse and violent behaviour. Treatments for alcohol misuse with offenders are therefore justified on the grounds that they may reduce violent behaviour and thus re-offending. The current paper tested whether a 10-session CBT intervention with offenders still in prison would produce improvements across three time points (pre, post and follow up) in self-reported alcohol expectancies, aggressiveness, impulsivity, and self-efficacy in managing alcohol use and violent behaviour. The programme focussed on educating participants on the relationship between alcohol use and violence, modifying unhelpful cognitions, and providing skills based training to manage potential triggers. Data from 49 offenders in prison were collected pre-intervention, post-intervention, and at three month follow up. Long term improvements (from pre- to post-intervention and follow up) were observed with respect to alcohol expectancies (in terms of sociability and liquid courage), impulsive responding to negative affect triggers, trait anger, and confidence in managing alcohol use and offending behaviour. These findings provide preliminary evidence for the efficacy of the CBT programme in reducing harmful alcohol use and associated violence. Limitations and recommendations for future evaluation of the intervention are discussed.

BACKGROUND: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. METHODS/DESIGN: This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. DISCUSSION: This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02649231. Registered on 5 January 2016.

Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.

Cognitive control theories attribute action control to executive processes that modulate behavior based
on expectancy or task rules. Here we examined corticospinal excitability and behavioral performance
in a go/no-go task. Go and no-go trials were presented in runs of 5, and runs alternated predictably. At
the beginning of each trial, subjects indicated whether they expected a go trial or a no-go trial.
Analyses revealed that subjects immediately adjusted their expectancy ratings when a new run started.
However, motor excitability was primarily associated with the properties of the previous trial, rather
than the predicted properties of the current trial. We also observed a large go latency cost at the
beginning of a go run. These findings indicate that actions in predictable environments are
substantially influenced by previous events, even if this goes against conscious expectancies about
upcoming events.

Is human Pavlovian conditioning driven by a unitary, propositional system (as claimed by Mitchell, De Houwer, & Lovibond, 2009) or by dual systems; one under conscious control, symbolic in nature, and requiring effort to deploy, and the other utilizing associative processes and automatic in its operation (McLaren, Green, & Mackintosh, 1994)? Past research has suggested that for electrodermal conditioning to occur in humans, conscious awareness of the contingencies is necessary to produce conditioned responding (e.g. Hinchy, Lovibond, & Ter-Horst, 1995), as predicted by single process theories that attribute the conditioned response (CR) to conscious expectancy of the shock. In this article, the authors examined the Perruchet effect (Perruchet, 1985), using an electrodermal paradigm to determine whether there is any role for associative processes in human electrodermal conditioning. The authors attempted to replicate the basic effect, whereby expectancy of an unconditioned stimulus (US) increases over a run of nonreinforced trials while the CR to the conditional stimulus (CS) declines, and the complementary pattern in which expectancy decreases over a run of reinforced trials while the CR to the CS grows in strength. In line with these patterns, the change in skin conductance response (our CR) as a function of US run length was found to follow a linear trend opposite to that of conscious expectancy of shock with respect to US run length. This dissociation supports a dual-processing system account of human Pavlovian conditioning, with conscious, controlled processes governing expectancy (and subject to the gambler's fallacy), whereas automatic, associative processes determine at least some of the strength of the CR to the CS.