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Objective Cerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels). Methods We used immunofluorescence microscopy and independent scoring, by two assessors blinded to the CM status, to assess MMP8 expression, extravascular fibrinogen as an indicator of vascular leak and their co‐localisation in the retinal microvasculature. Results In ‘true‐CM’ subjects, MMP8 staining was invariably associated with sequestered parasites and a median of 88% (IQR = 74–91%) of capillaries showed MMP8 staining, compared with 14% (IQR = 3.8–24%) in ‘faux‐CM’ (P‐value = 0.001). 41% (IQR = 28–49%) of capillaries in ‘true‐CM’ subjects showed co‐localisation of extravascular fibrinogen leak and MMP8 staining, compared with 1.8% of capillaries in ‘faux‐CM’ (IQR = 0–3.9%, P‐value = 0.01). Vascular leak was rare in the absence of MMP8 staining. Conclusion Matrix metallopeptidase 8 was extensively expressed in retinal capillaries of Malawian children with malarial retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 as a cause of the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling., To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in cerebral malaria (CM), we examined its expression and association with extravascular fibrinogen leak in a case‐control study of post‐mortem retinal samples from 13 Malawian children. MMP8 was extensively expressed in retinal capillaries of children with CM retinopathy and strongly associated with vascular leak. Our findings implicate MMP8 in the vascular endothelial barrier disruption in CM, which may precipitate fatal brain swelling.

Background Positive psychology interventions may usefully treat depression and can be delivered online to reduce the treatment gap. However, little is known about how acceptable patients find this approach. To address this, the present study interviewed recent users of a positive psychology self-help website. Methods In-depth semi-structured interviews explored the experiences of twenty-three participants from a larger feasibility study. A stratified purposive sampling strategy selected participants with varying intervention experience according to their intervention logins, as well as varying age, gender and depressive symptoms. Framework analysis was used to explore patterns and linkages within and between participants' accounts. Results Acceptability varied between participants. Those who found it more acceptable felt it was relevant to their depression and reported feeling empowered by a self-help approach. Conversely, participants for whom it was less acceptable perceived the positive focus irrelevant to their depression and found the emphasis on self-action unsupportive. Conclusions The acceptability of an online positive psychology intervention may be facilitated by a patients' preference for a psychological focus on the positive. However, patients may also have distinct preferences for online self-help. Future research should investigate the importance of the therapeutic orientation of online self-help interventions and whether patients' preferences for these can be reliably identified. This could help to target online self-help in clinical practice., Highlights • Acceptability of positive psychology varied between participants. • Acceptability was facilitated by perceived relevance of positivity to depression. • Acceptability was facilitated by perceived empowerment of a self-help approach.

This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart's Health NHS Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Background Positive psychology interventions are brief self-adminstered exercises designed to promote positive emotions, behaviours, or thoughts. They are potentially effective for reducing depression and are considered suitable for online dissemination to people with depression and related conditions, as they are assumed to be more acceptable than traditional symptom-focused approaches. However, there is little investigation into perceived acceptability and potential factors that might affect it. This might limit the development and evaluation of effective interventions. Methods Semi-structured interviews with patients with depression and/or anxiety (n = 18) and professionals, including GPs and psychologists (n = 5) were conducted on their perceptions of a proposed online intervention using positive psychology. Thematic analysis, according to Braun and Clarke, was used to identify meaningful patterns in the data. Results Four key themes were identified. The fit between the positive psychological approach and the patient’s context, including their personality, symptoms and other treatments, was important in determining acceptability. Social aspects of interventions were thought to facilitate acceptability, as long as these were balanced. Support was identified as important in facilitating intervention suitability, although it was not without limitations. Finally, participants identified how design features can enhance acceptability. Conclusions The findings suggest that positive psychology interventions might not be acceptable to all and that specific exercises might be more or less appropriate to deliver online. Design aspects can help to facilitate acceptability, beyond the psychological content. These findings may inform the design of future online psychology interventions for people with depression and anxiety, which can then be evaluated in future research. Electronic supplementary material The online version of this article (10.1186/s12888-018-1812-x) contains supplementary material, which is available to authorized users.

BackgroundAt least 100,000 patients with schizophrenia receive care from community mental health teams (CMHTs) in England. These patients have regular meetings with clinicians, who assess them, engage them in treatment and co-ordinate care. As these routine meetings are not commonly guided by research evidence, a new intervention, DIALOG, was previously designed to structure consultations. Using a hand-held computer, clinicians asked patients to rate their satisfaction with eight life domains and three treatment aspects, and to indicate whether or not additional help was needed in each area, with responses being graphically displayed and compared with previous ratings. In a European multicentre trial, the intervention improved patients’ quality of life over a 1-year period. The current programme builds on this research by further developing DIALOG in the UK.Research questions(1) How can the practical procedure of the intervention be improved, including the software used and the design of the user interface? (2) How can elements of resource-oriented interventions be incorporated into a clinician manual and training programme for a new, more extensive ‘DIALOG+’ intervention? (3) How effective and cost-effective is the new DIALOG+ intervention in improving treatment outcomes for patients with schizophrenia or a related disorder? (4) What are the views of patients and clinicians regarding the new DIALOG+ intervention?MethodsWe produced new software on a tablet computer for CMHTs in the NHS, informed by analysis of videos of DIALOG sessions from the original trial and six focus groups with 18 patients with psychosis. We developed the new ‘DIALOG+’ intervention in consultation with experts, incorporating principles of solution-focused therapy when responding to patients’ ratings and specifying the procedure in a manual and training programme for clinicians. We conducted an exploratory cluster randomised controlled trial with 49 clinicians and 179 patients with psychosis in East London NHS Foundation Trust, comparing DIALOG+ with an active control. Clinicians working as care co-ordinators in CMHTs (along with their patients) were cluster randomised 1 : 1 to either DIALOG+ or treatment as usual plus an active control, to prevent contamination. Intervention and control were to be administered monthly for 6 months, with data collected at baseline and at 3, 6 and 12 months following randomisation. The primary outcome was subjective quality of life as measured on the Manchester Short Assessment of Quality of Life; secondary outcomes were also measured. We also established the cost-effectiveness of the DIALOG intervention using data from the Client Service Receipt Inventory, which records patients’ retrospective reports of using health- and social-care services, including hospital services, outpatient services and medication, in the 3 months prior to each time point. Data were supplemented by the clinical notes in patients’ medical records to improve accuracy. We conducted an exploratory thematic analysis of 16 video-recorded DIALOG+ sessions and measured adherence in these videos using a specially developed adherence scale. We conducted focus groups with patients (n = 19) and clinicians (n = 19) about their experiences of the intervention, and conducted thematic analyses. We disseminated the findings and made the application (app), manual and training freely available, as well as producing a protocol for a definitive trial.ResultsPatients receiving the new intervention showed more favourable quality of life in the DIALOG+ group after 3 months (effect size: Cohen’sd = 0.34), after 6 months (Cohen’sd = 0.29) and after 12 months (Cohen’sd = 0.34). An analysis of video-recorded DIALOG+ sessions showed inconsistent implementation, with adherence to the intervention being a little over half of the possible score. Patients and clinicians from the DIALOG+ arm of the trial reported many positive experiences with the intervention, including better self-expression and improved efficiency of meetings. Difficulties reported with the intervention were addressed by further refining the DIALOG+ manual and training. Cost-effectiveness analyses found a 72% likelihood that the intervention both improved outcomes and saved costs.LimitationsThe research was conducted solely in urban east London, meaning that the results may not be broadly generalisable to other settings.Conclusions(1) Although services might consider adopting DIALOG+ based on the existing evidence, a definitive trial appears warranted; (2) applying DIALOG+ to patient groups with other mental disorders may be considered, and to groups with physical health problems; (3) a more flexible use with variable intervals might help to make the intervention even more acceptable and effective; (4) more process evaluation is required to identify what mechanisms precisely are involved in the improvements seen in the intervention group in the trial; and (5) what appears to make DIALOG+ effective is that it is not a separate treatment and not a technology that is administered by a specialist; rather, it changes and utilises the existing therapeutic relationship between patients and clinicians in CMHTs to initiate positive change, helping the patients to improve their quality of life.Future researchFuture studies should include a definitive trial on DIALOG+ and test the effectiveness of the intervention with other populations, such as people with depression.Trial registrationCurrent Controlled Trials ISRCTN34757603.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Essential criteria for the methodological quality and validity of randomized controlled trials are the drop-out rates from both the experimental intervention and the study as a whole. This systematic review and meta-analysis assessed these drop-out rates in non-pharmacological schizophrenia trials. A systematic literature search was used to identify relevant trials with ≥100 sample size and to extract the drop-out data. The rates of drop-out from the experimental intervention and study were calculated with meta-analysis of proportions. Meta-regression was applied to explore the association between the study and sample characteristics and the drop-out rates. 43 RCTs were found, with drop-out from intervention ranging from 0% to 63% and study drop-out ranging from 4% to 71%. Meta-analyses of proportions showed an overall drop-out rate of 14% (95% CI: 13-15%) at the experimental intervention level and 20% (95% CI: 17-24%) at the study level. Meta-regression showed that the active intervention drop-out rates were predicted by the number of intervention sessions. In non-pharmacological schizophrenia trials, drop-out rates of less than 20% can be achieved for both the study and the experimental intervention. A high heterogeneity of drop-out rates across studies shows that even lower rates are achievable.

Positive psychotherapy (PPT) stems from the positive psychology movement and is a multicomponent model promoting therapeutic change by developing engagement, pleasure, and meaning. There is some evidence it is effective for depression. PPT is recommended as a flexible model that can be applied to other patient groups alongside other treatments approaches. However, it remains unclear which of the many components are applied. The study aimed to identify how PPT is applied in mental health care.We systematically searched online databases, including Medline, Embase, PsycINFO, British Nursing Index, Cumulative Index of Nursing and Applied Health, and Cochrane registers (CENTRAL), and completed complementary hand and citation searches. Narrative synthesis was used for analysis.A total of 12 papers (from 9 studies) widely applied some PPT components (e.g., blessings journal, character strengths) and scarcely applied others (e.g., satisficing plan or family strengths tree). However, papers poorly described the intervention and rationale for applying components.Given the lack of rationale for applying PPT, further research is needed to establish which components are acceptable and feasible for use in different patient groups and settings.

Background: DIALOG+ was developed as a computer-mediated intervention, consisting of a structured assessment of patients' concerns combined with a solution-focused approach to initiate change. This study tested the effectiveness of DIALOG+ in the community treatment of patients with psychosis. Method: This was a pragmatic, exploratory, parallel-group, cluster-randomised controlled trial. Clinicians within community teams - along with patients with psychosis under their care - were randomised to use DIALOG+ once per month for 6 months or an active control. The primary outcome (subjective quality of life, SQOL) and secondary outcomes were assessed after 3, 6 and 12 months by blinded assessors and analysed using mixed-effect models. Results: A total of 49 clinicians and 179 patients were randomised. Implementation of DIALOG+ was variable, with an average of 1.8 sessions (SD = 1.6) in the first 3 months and 1.1 (SD = 1.2) in the following 3 months. Patients in the DIALOG+ arm had better SQOL at 3, 6 and 12 months (p = 0.035, 0.058 and 0.014, respectively; Cohen's d = 0.29-0.34). They also had significantly fewer unmet needs at 3 and 6 months, fewer general psychopathological symptoms at all time points and better objective social outcomes at 12 months, with no significant differences in other outcomes. Overall care costs were lower in the intervention group. Conclusion: Despite variable implementation, DIALOG+ is a beneficial intervention for community patients with psychosis. As a non-expensive and potentially cost-saving, generic intervention, DIALOG+ may be widely used and may improve the effectiveness of community treatment. Further trials should test DIALOG+ in different patient groups and contexts.

It can take a lot of courage to leave a stable job and take a break from practice, but, as Sophie Walsh has found, doing so can open up a whole range of new interests and passions.

Objectives To review systematically the literature on patients’ experiences of, and participation in, technology-based monitoring of mental health symptoms. This practice was defined as patients monitoring their mental health symptoms, emotions or behaviours outside of routine clinical appointments by submitting symptom data using technology, with feedback arising from the data (for example, supportive messages or symptom summaries, being sent to the patient, clinician or carer). Design Systematic review following PRISMA guidelines of studies evaluating technology-based symptom monitoring. Tools from narrative synthesis were used to analyse quantitative findings on participation rates and qualitative findings on patient views. Data sources PubMed, EMBASE, PsycINFO, BNI, CINAHL, Cochrane Registers and Web of Science electronic databases were searched using a combination of ‘psychiatry’, ‘symptom monitoring’ and ‘technology’ descriptors. A secondary hand search was performed in grey literature and references. Results 57 papers representing 42 studies met the inclusion criteria for the review. Technology-based symptom monitoring was used for a range of mental health conditions, either independently of a specific therapeutic intervention or as an integrated component of therapeutic interventions. The majority of studies reported moderate-to-strong rates of participation, though a third reported lower rates. Qualitative feedback suggests that acceptability of monitoring is related to perceived validity, ease of practice, convenient technology, appropriate frequency and helpfulness of feedback, as well as the impact of monitoring on participants’ ability to manage health and personal relationships. Conclusions Such symptom monitoring practices appear to be well accepted and may be a feasible complement to clinical practice. However, there is limited availability of data and heterogeneity of studies. Future research should examine robustly patients’ role in the development and evaluation of technology-based symptom monitoring in order to maximise its clinical utility.

Poor retention of participants in randomised controlled trials (RCTs) is a commonly recognised issue. Attrition rates in studies across different disciplines have been reported to vary from 5% to 70%. There is no systematic evidence reporting attrition rates specifically in trials involving people with severe and fluctuating mental health conditions. To purpose of this review was to synthesise the reported retention rates in RCTs evaluating non-pharmacological interventions for psychosis and identify study characteristics associated with high dropout. Five key electronic databases and key journals were systematically searched to identify studies published between 1996 and 2015. The search included large scale RCTs (n≥100 at baseline) including adults with psychosis receiving non-pharmacological interventions. Data extraction included participant flow information reported in the Consolidated Standards of Reporting Trials (CONSORT) statement or flow diagram. Random effects logistic regression analysis was conducted to examine effects of key study characteristics on participation rates. 62 papers were included in the review. This paper will discuss the participation rates reported in RCTs, the quality of reporting in publications, and the study characteristics that predict participation rates.