Developing patient-centred, feasible alternative care for adult emergency department users with epilepsy: protocol for the mixed-methods observational 'Collaborate' project.

INTRODUCTION: Emergency department (ED) visits for epilepsy are common, costly, often clinically unnecessary and typically lead to little benefit for epilepsy management. An 'Alternative Care Pathway' (ACP) for epilepsy, which diverts people with epilepsy (PWE) away from ED when '999' is called and leads to care elsewhere, might generate savings and facilitate improved ambulatory care. It is unknown though what features it should incorporate to make it acceptable to persons from this particularly vulnerable target population. It also needs to be National Health Service (NHS) feasible. This project seeks to identify the optimal ACP configuration. METHODS AND ANALYSIS: Mixed-methods project comprising three-linked stages. In Stage 1, NHS bodies will be surveyed on ACPs they are considering and semi-structured interviews with PWE and their carers will explore attributes of care important to them and their concerns and expectations regarding ACPs. In Stage 2, Discrete Choice Experiments (DCE) will be completed with PWE and carers to identify the relative importance placed on different care attributes under common seizure scenarios and the trade-offs people are willing to make. The uptake of different ACP configurations will be estimated. In Stage 3, two Knowledge Exchange workshops using a nominal group technique will be run. NHS managers, health professionals, commissioners and patient and carer representatives will discuss DCE results and form a consensus on which ACP configuration best meets users' needs and is NHS feasible. ETHICS AND DISSEMINATION: Ethical approval: NRES Committee (19/WM/0012) and King's College London ethics Committee (LRS-18/19-10353). Primary output will be identification of optimal ACP configuration which should be prioritised for implementation and evaluation. A pro-active dissemination strategy will make those considering developing or supporting an epilepsy ACP aware of the project and opportunities to take part in it. It will also ensure they are informed of its findings. PROJECT REGISTRATION NUMBER: Researchregistry4723.

Treating repetitive suicidal intrusions using eye movements: study protocol for a multicenter randomized clinical trial.

BACKGROUND: Suicide is a major public health problem, and it remains unclear which processes link suicidal ideation and plans to the act of suicide. Growing evidence shows that the majority of suicidal patients diagnosed with major depression or bipolar disorder report repetitive suicide-related images and thoughts (suicidal intrusions). Various studies showed that vividness of negative as well as positive intrusive images may be reduced by dual task (e.g. eye movements) interventions taxing the working memory. We propose that a dual task intervention may also reduce frequency and intensity of suicidal imagery and may be crucial in preventing the transition from suicidal ideation and planning to actual suicidal behaviour. This study aims a) to evaluate the effectiveness of an Eye Movement Dual Task (EMDT) add-on intervention targeting suicidal imagery in depressed patients, b) to explore the role of potential moderators and mediators in explaining the effect of EMDT, and c) to evaluate the cost-effectiveness of EMDT. METHODS: We will conduct a multi-center randomized clinical trial (RCT) evaluating the effects of EMDT in combination with usual care (n = 45) compared to usual care alone (n = 45). Participants will fill in multiple online batteries of self-report questionnaires as well as complete a semi-structured interview (Intrusion Interview), and online computer tasks. The primary outcome is the frequency and intrusiveness of suicidal imagery. Furthermore, the vividness, emotionality, and content of the suicidal intrusions are evaluated; secondary outcomes include: suicidal behaviour and suicidal ideation, severity of depression, psychological symptoms, rumination, and hopelessness. Finally, potential moderators and mediators are assessed. DISCUSSION: If proven effective, EMDT can be added to regular treatment to reduce the frequency and vividness of suicidal imagery. TRIAL REGISTRATION: The study has been registered on October 17th, 2018 at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR7563 ).

Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma.

Mental Imagery-Based Training to Modify Mood and Cognitive Bias in Adolescents: Effects of Valence and Perspective.

Mental imagery has a powerful impact on emotion and cognitive processing in adults, and is implicated in emotional disorders. Research suggests the perspective adopted in mental imagery modulates its emotional impact. However, little is known about the impact of mental imagery in adolescence, despite adolescence being the key time for the onset of emotional dysfunction. We administered computerised positive versus mixed valence picture-word mental imagery training to male adolescent participants (N = 60, aged 11-16 years) across separate field and observer perspective sessions. Positive mood increased more following positive than mixed imagery; pleasantness ratings of ambiguous pictures increased following positive versus mixed imagery generated from field but not observer perspective; negative interpretation bias on a novel scrambled sentences task was smaller following positive than mixed imagery particularly when imagery was generated from field perspective. These findings suggest positive mental imagery generation alters mood and cognition in male adolescents, with the latter moderated by imagery perspective. Identifying key components of such training, such as imagery perspective, extends understanding of the relationship between mental imagery, mood, and cognition in adolescence.

Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology.

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series.

Treatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals' mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).

Intrusive memories to traumatic footage: the neural basis of their encoding and involuntary recall.

BACKGROUND: A hallmark symptom after psychological trauma is the presence of intrusive memories. It is unclear why only some moments of trauma become intrusive, and how these memories involuntarily return to mind. Understanding the neural mechanisms involved in the encoding and involuntary recall of intrusive memories may elucidate these questions. METHOD: Participants (n = 35) underwent functional magnetic resonance imaging (fMRI) while being exposed to traumatic film footage. After film viewing, participants indicated within the scanner, while undergoing fMRI, if they experienced an intrusive memory of the film. Further intrusive memories in daily life were recorded for 7 days. After 7 days, participants completed a recognition memory test. Intrusive memory encoding was captured by comparing activity at the time of viewing 'Intrusive scenes' (scenes recalled involuntarily), 'Control scenes' (scenes never recalled involuntarily) and 'Potential scenes' (scenes recalled involuntarily by others but not that individual). Signal change associated with intrusive memory involuntary recall was modelled using finite impulse response basis functions. RESULTS: We found a widespread pattern of increased activation for Intrusive v. both Potential and Control scenes at encoding. The left inferior frontal gyrus and middle temporal gyrus showed increased activity in Intrusive scenes compared with Potential scenes, but not in Intrusive scenes compared with Control scenes. This pattern of activation persisted when taking recognition memory performance into account. Intrusive memory involuntary recall was characterized by activity in frontal regions, notably the left inferior frontal gyrus. CONCLUSIONS: The left inferior frontal gyrus may be implicated in both the encoding and involuntary recall of intrusive memories.

Mental imagery, emotion and psychopathology across child and adolescent development.

Mental imagery-based interventions are receiving increasing interest for the treatment of psychological disorders in adults. This is based on evidence that mental imagery potently influences the experience of emotion in non-clinical samples, and that a number of psychological disorders are marked by syndrome-specific, distressing abnormalities in mental imagery. During childhood and adolescence, neurocognitive development impacting mental imagery processes may moderate its relationship with clinically-relevant emotional symptoms at a number of potential loci. Crucially, these changes could impact vulnerability to distressing mental imagery and the efficacy of mental imagery-based clinical interventions. This review synthesises evidence pertaining to developmental changes in the role and content of mental imagery, and in the cognitive sub-processes required to generate and sustain mental images. Subsequently, we discuss implications for understanding the developmental relationship between mental imagery, emotion and psychopathology. Translational cognitive neuroscience research investigating the content, emotional impact and neurocognitive substrates of mental imagery across development may reveal insights into trajectories of vulnerability to symptoms of a number of psychological disorders. If proper consideration is given to developmental factors, techniques based on mental imagery may be valuable as part of a treatment armoury for child and adolescent clinical populations and those at risk of emotional disorders.

The neural basis of flashback formation: the impact of viewing trauma.

BACKGROUND: Psychological traumatic events, such as war or road traffic accidents, are widespread. A small but significant proportion of survivors develop post-traumatic stress disorder (PTSD). Distressing, sensory-based involuntary memories of trauma (henceforth 'flashbacks') are the hallmark symptom of PTSD. Understanding the development of flashbacks may aid their prevention. This work is the first to combine the trauma film paradigm (as an experimental analogue for flashback development) with neuroimaging to investigate the neural basis of flashback aetiology. We investigated the hypothesis that involuntary recall of trauma (flashback) is determined during the original event encoding. Method A total of 22 healthy volunteers viewed a traumatic film whilst undergoing functional magnetic resonance imaging (fMRI). They kept a 1-week diary to record flashbacks to specific film scenes. Using a novel prospective fMRI design, we compared brain activation for those film scenes that subsequently induced flashbacks with both non-traumatic control scenes and scenes with traumatic content that did not elicit flashbacks ('potentials'). RESULTS: Encoding of scenes that later caused flashbacks was associated with widespread increases in activation, including in the amygdala, striatum, rostral anterior cingulate cortex, thalamus and ventral occipital cortex. The left inferior frontal gyrus and bilateral middle temporal gyrus also exhibited increased activation but only relative to 'potentials'. Thus, these latter regions appeared to distinguish between traumatic content that subsequently flashed back and comparable content that did not. CONCLUSIONS: Results provide the first prospective evidence that the brain behaves differently whilst experiencing emotional events that will subsequently become involuntary memories - flashbacks. Understanding the neural basis of analogue flashback memory formation may aid the development of treatment interventions for this PTSD feature.

Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder.

Bipolar disorder is a psychiatric condition characterized by episodes of elevated mood interspersed with episodes of depression. While treatment developments and understanding the disruptive nature of this illness have focused on these episodes, it is also evident that some patients may have chronic week-to-week mood instability. This is also a major morbidity. The longitudinal pattern of this mood instability is poorly understood as it has, until recently, been difficult to quantify. We propose that understanding this mood variability is critical for the development of cognitive neuroscience-based treatments. In this study, we develop a time-series approach to capture mood variability in two groups of patients with bipolar disorder who appear on the basis of clinical judgement to show relatively stable or unstable illness courses. Using weekly mood scores based on a self-rated scale (quick inventory of depressive symptomatology-self-rated; QIDS-SR) from 23 patients over a 220-week period, we show that the observed mood variability is nonlinear and that the stable and unstable patient groups are described by different nonlinear time-series processes. We emphasize the necessity in combining both appropriate measures of the underlying deterministic processes (the QIDS-SR score) and noise (uncharacterized temporal variation) in understanding dynamical patterns of mood variability associated with bipolar disorder.

New Genotypes of Fusarium oxysporum f. sp. vasinfectum from the Southeastern United States.

Sixty-one isolates of Fusarium oxysporum f. sp. vasinfectum were collected from cotton plants (Gossypium spp.) with symptoms of Fusarium wilt to determine the composition of races present in the southeastern United States. Analysis of partial sequences of the translation elongation factor gene revealed four novel genotypes, as well as the presence of races 3 and 8 for the first time in the United States outside of California. The majority of isolates (16 of 27) sampled from Arkansas were novel genotypes. A subset of isolates representing the novel genotypes was compared with previously described races using sequences from translation elongation factor, phosphate permase, and ß-tubulin genes and their pathogenicity on a total of six Upland (Gossypium hirsutum) and Pima (G. barbadense) cotton cultivars. Two of the novel genotypes belonged to a clade containing races 1, 2, 4, 6, and 8 and two shared ancestry with race 3. All new genotypes were pathogenic to at least some of the cotton cultivars tested. The Pima cv. Phytogen 800 was relatively resistant to all genotypes of the pathogen. These results indicate that the population of F. oxysporum f. sp. vasinfectum in the southeastern United States is more diverse than previously recognized.