Autobiographical episodic memory-based training for the treatment of mood, anxiety and stress-related disorders: A systematic review and meta-analysis.

We review evidence for training programmes that manipulate autobiographical processing in order to treat mood, anxiety, and stress-related disorders, using the GRADE criteria to judge evidence quality. We also position the current status of this research within the UK Medical Research Council's (2000, 2008) framework for the development of novel interventions. A literature search according to PRISMA guidelines identified 15 studies that compared an autobiographical episodic memory-based training (AET) programme to a control condition, in samples with a clinician-derived diagnosis. Identified AET programmes included Memory Specificity Training (Raes, Williams, & Hermans, 2009), concreteness training (Watkins, Baeyens, & Read, 2009), Competitive Memory Training (Korrelboom, van der Weele, Gjaltema, & Hoogstraten, 2009), imagery-based training of future autobiographical episodes (Blackwell & Holmes, 2010), and life review/reminiscence therapy (Arean et al., 1993). Cohen's d was calculated for between-group differences in symptom change from pre- to post-intervention and to follow-up. We also completed meta-analyses for programmes evaluated across multiple studies, and for the overall effect of AET as a treatment approach. Results demonstrated promising evidence for AET in the treatment of depression (d=0.32), however effect sizes varied substantially (from -0.18 to 1.91) across the different training protocols. Currently, research on AET for the treatment of anxiety and stress-related disorders is not yet at a stage to draw firm conclusions regarding efficacy as there were only a very small number of studies which met inclusion criteria. AET offers a potential avenue through which low-intensity treatment for affective disturbance might be offered

The Impact of Affective Context on Autobiographical Recollection in Depression.

Across two studies we investigated the influence of contextual cues on autobiographical memory recall. In Study 1, participants (N = 37) with major depressive disorder, in episode or in varying degrees of remission, were administered a Negative Autobiographical Memory Task (NAMT) that required them to retrieve negatively valenced memories in response to positive cue words (a positive context). We reasoned that increased depression symptom severity would be associated with a reduced ability to override priming from this disadvantageous context. Consequently, we hypothesized that increased depressive severity would counterintuitively be associated with reduced negativity ratings for retrieved personal memories to positive cues on the NAMT. This hypothesis was supported. Study 2, using a community sample (N = 63), demonstrated that a similar reduction in memory negativity was observed in individuals with lower working memory capacity-an index of executive control. Implications for autobiographical memory and executive training paradigms for depression are discussed

Memory Flexibility training (MemFlex) to reduce depressive symptomatology in individuals with major depressive disorder: study protocol for a randomised controlled trial.

BACKGROUND: Major depressive disorder (MDD) is associated with chronic biases in the allocation of attention and recollection of personal memories. Impaired flexibility in attention and autobiographical memory retrieval is seen to both maintain current symptoms and predict future depression. Development of innovative interventions to reduce maladaptive cognitive patterns and improve cognitive flexibility in the domain of memory may therefore advance current treatment approaches for depression. Memory specificity training and cognitive bias modification techniques have both shown some promise in improving cognitive flexibility. Here we outline plans for a trial of an innovative memory flexibility training programme, MemFlex, which advances current training techniques with the aim of improving flexibility of autobiographical memory retrieval. This trial seeks to estimate the efficacy of MemFlex, provide data on feasibility, and begin to explore mechanisms of change. METHODS/DESIGN: We plan a single-blind, randomised, controlled, patient-level trial in which 50 individuals with MDD will complete either psychoeducation (n = 25) or MemFlex (n = 25). After completing pre-treatment measures and an orientation session, participants complete eight workbook-based sessions at home. Participants will then be assessed at post-treatment and at 3 month follow-up. The co-primary outcomes are depressive symptoms and diagnostic status at 3 month follow-up. The secondary outcomes are memory flexibility at post-treatment and number of depression free days at 3 month follow-up. Other process outcomes and mediators of any treatment effects will also be explored. DISCUSSION: This trial will establish the efficacy of MemFlex in improving memory flexibility, and reducing depressive symptoms. Any effects on process measures related to relapse may also indicate whether MemFlex may be helpful in reducing vulnerability to future depressive episodes. The low-intensity and workbook-based format of the programme may improve access to psychological therapies, and, if encouraging, the results of this study will provide a platform for later-phase trials. TRIAL REGISTRATION: NCT02371291 (ClinicalTrials.gov), registered 9 February 2015

Translating the Cognitive Model of PTSD to the Treatment of Very Young Children: A Single Case Study of an 8-Year-Old Motor Vehicle Accident Survivor.

Posttraumatic stress disorder (PTSD) is a clinical condition that occurs after a discrete traumatic event, such as an accident or assault. Research into PTSD has primarily been adult-focused; however, there is a growing body of evidence evaluating the theory and treatment of PTSD in young children. Consequently, cognitive behavior therapy (CBT) interventions for PTSD in youth have been developed that focus on 3 core components of the cognitive model-a disorganized memory of the trauma, maladaptive appraisals of the trauma and its effects (meanings), and dysfunctional coping mechanisms (management). Here, we describe the extension of this treatment approach (termed CBT-3M) to very young children (3-8 years) through the case of Dylan, an 8-year-old motor vehicle accident survivor. This serves as an illustration of the underlying theory and its successful application. Further work is intended to provide evidence of the efficacy of this treatment via an ongoing treatment trial

Study protocol for a randomised, controlled platform trial estimating the effect of autobiographical Memory Flexibility training (MemFlex) on relapse of recurrent major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a chronic condition. Although current treatment approaches are effective in reducing acute depressive symptoms, rates of relapse are high. Chronic and inflexible retrieval of autobiographical memories, and in particular a bias towards negative and overgeneral memories, is a reliable predictor of relapse. This randomised controlled single-blind trial will determine whether a therapist-guided self-help intervention to ameliorate autobiographical memory biases using Memory Flexibility training (MemFlex) will increase the experience of depression-free days, relative to a psychoeducation control condition, in the 12 months following intervention. METHODS AND ANALYSIS: Individuals (aged 18 and above) with a diagnosis of recurrent MDD will be recruited when remitted from a major depressive episode. Participants will be randomly allocated to complete 4 weeks of a workbook providing either MemFlex training, or psychoeducation on factors that increase risk of relapse. Assessment of diagnostic status, self-report depressive symptoms, depression-free days and cognitive risk factors for depression will be completed post-intervention, and at 6 and 12 months follow-up. The cognitive target of MemFlex will be change in memory flexibility on the Autobiographical Memory Test- Alternating Instructions. The primary clinical endpoints will be the number of depression-free days in the 12 months following workbook completion, and time to depressive relapse. ETHICS AND DISSEMINATION: Ethics approval has been granted by the NHS National Research Ethics Committee (East of England, 11/H0305/1). Results from this study will provide a point-estimate of the effect of MemFlex on depressive relapse, which will be used to inform a fully powered trial evaluating the potential of MemFlex as an effective, low-cost and low-intensity option for reducing relapse of MDD. TRIAL REGISTRATION NUMBER: NCT02614326.This work is supported by a grant to TD from the UK Medical Research Council, grant number MC_US_A060_0019

Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium

Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 ± 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 ± 1.3 μg/min [arrival intensive care unit (ICU) 35.4°C] to 4.6 ± 1.0 μg/min (34°C) and 2.8 ± 0.5 μg/min (33°C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 ± 1.7 bpm (arrival ICU) to 77.3 ± 1.5 bpm (34°C) and 70.3 ± 1.4 bpm (33°C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 ± 23% at 27°C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca2+ content, but can be elicited even when the SR Ca2+ release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca2+ sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca2+-sensitivity

Trauma-focused cognitive behaviour therapy versus treatment as usual for post traumatic stress disorder (PTSD) in young children aged 3 to 8 years: study protocol for a randomised controlled trial.

BACKGROUND: Following horrific or life-threatening events approximately 10 to 15% of young children develop post traumatic stress disorder (PTSD). The symptoms of this disorder are distressing - nightmares, flashbacks, anger outbursts and disturbed play. These symptoms cause major disruption to a child's functioning and, if left untreated, can persist for many years. As yet, there are no established empirically-validated treatments for PTSD in young children. Trauma-focused cognitive behaviour therapy (TF-CBT) is a psychological intervention that is effective in treating the disorder in older children (8 to 12 years), adolescents and adults. This study examines TF-CBT adapted for children aged between 3 and 8 years. METHODS/DESIGN: This protocol describes a two-arm exploratory randomised controlled trial comparing TF-CBT to treatment as usual (TAU) in children aged 3 to 8 years with a principal diagnosis of PTSD following a single-event discrete trauma. Using a half-crossover design, 44 participants will be randomly allocated to receive the intervention or to receive TAU. Those allocated to TAU will be offered TF-CBT at the end of the 'treatment' period (approximately 12 weeks) if still indicated. The primary outcome is PTSD diagnosis according to DSM-5 criteria for children 6 years and younger at post-treatment. Secondary outcomes include effects on co-morbid diagnoses and changes in emotion and trauma symptoms at each of the follow-up points (post-treatment, 3-months, 12-months). Additionally, broader efficacy will be considered with regard to treatment feasibility, acceptability and service utilisation. The key targets of the intervention are trauma memory, the interpretation of the meaning of the event, and the management of symptoms. DISCUSSION: This is the first European trial to examine the efficacy of TF-CBT in alleviating PTSD in very young children. As well as providing much-needed data on the utility of the intervention, this exploratory trial will also allow us to gather important information about the feasibility of delivering the treatment in UK National Health Service (NHS) settings, and its acceptability to the children and their families. This study will highlight aspects of the intervention that need improvement or modification in preparation for a full-scale evaluation in a larger sample. TRIAL REGISTRATION: ISRCTN35018680 , registered on 18 November 2013

Development and validation of explainable machine learning models for risk of mortality in transcatheter aortic valve implantation: TAVI risk machine scores.

AIMS Identification of high-risk patients and individualized decision support based on objective criteria for rapid discharge after transcatheter aortic valve implantation (TAVI) are key requirements in the context of contemporary TAVI treatment. This study aimed to predict 30-day mortality following TAVI based on machine learning (ML) using data from the German Aortic Valve Registry. METHODS AND RESULTS Mortality risk was determined using a random forest ML model that was condensed in the newly developed TAVI Risk Machine (TRIM) scores, designed to represent clinically meaningful risk modelling before (TRIMpre) and in particular after (TRIMpost) TAVI. Algorithm was trained and cross-validated on data of 22 283 patients (729 died within 30 days post-TAVI) and generalisation was examined on data of 5864 patients (146 died). TRIMpost demonstrated significantly better performance than traditional scores [C-statistics value, 0.79; 95% confidence interval (CI)] [0.74; 0.83] compared to Society of Thoracic Surgeons (STS) with C-statistics value 0.69; 95%-CI [0.65; 0.74]). An abridged (aTRIMpost) score comprising 25 features (calculated using a web interface) exhibited significantly higher performance than traditional scores (C-statistics value, 0.74; 95%-CI [0.70; 0.78]). Validation on external data of 6693 patients (205 died within 30 days post-TAVI) of the Swiss TAVI Registry confirmed significantly better performance for the TRIMpost (C-statistics value 0.75, 95%-CI [0.72; 0.79]) compared to STS (C-statistics value 0.67, CI [0.63; 0.70]). CONCLUSION TRIM scores demonstrate good performance for risk estimation before and after TAVI. Together with clinical judgement, they may support standardised and objective decision-making before and after TAVI

Affective enhancement of working memory is maintained in depression.

We currently know little about how performance on assessments of working memory capacity (WMC) that are designed to mirror the concurrent task demands of daily life are impacted by the presence of affective information, nor how those effects may be modulated by depression-a syndrome where sufferers report global difficulties with executive processing. Across 3 experiments, we investigated WMC for sets of neutral words in the context of processing either neutral or affective (depressogenic) sentences, which had to be judged on semantic accuracy (Experiments 1 and 2) or self-reference (Experiment 3). Overall, WMC was significantly better in the context of depressogenic compared with neutral sentences. However, there was no support for this effect being modulated by symptoms of depression (Experiment 1) or the presence of recurrent major depressive disorder (MDD; Experiments 2 and 3). Implications of these findings for cognitive theories of the role of WM in depression are discussed in the context of a growing body of research showing no support for a differential impact of depressogenic compared with neutral information on WM accuracy. (PsycINFO Database Recor