Automated virtual reality cognitive therapy versus virtual reality mental relaxation therapy for the treatment of persistent persecutory delusions in patients with psychosis (THRIVE): a parallel-group, single-blind, randomised controlled trial in England with mediation analyses.

BACKGROUND: Persecutory delusions are a major psychiatric problem that often do not respond sufficiently to standard pharmacological or psychological treatments. We developed a new brief automated virtual reality (VR) cognitive treatment that has the potential to be used easily in clinical services. We aimed to compare VR cognitive therapy with an alternative VR therapy (mental relaxation), with an emphasis on understanding potential mechanisms of action. METHODS: THRIVE was a parallel-group, single-blind, randomised controlled trial across four UK National Health Service trusts in England. Participants were included if they were aged 16 years or older, had a persistent (at least 3 months) persecutory delusion held with at least 50% conviction, reported feeling threatened when outside with other people, and had a primary diagnosis from the referring clinical team of a non-affective psychotic disorder. We randomly assigned (1:1) patients to either THRIVE VR cognitive therapy or VR mental relaxation, using a permuted blocks algorithm with randomly varying block size, stratified by severity of delusion. Usual care continued for all participants. Each VR therapy was provided in four sessions over approximately 4 weeks, supported by an assistant psychologist or clinical psychologist. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 2 (therapy mid-point), 4 (primary endpoint, end of treatment), 8, 16, and 24 weeks. The primary outcome was persecutory delusion conviction, assessed by the Psychotic Symptoms Rating Scale (PSYRATS; rated 0-100%). Outcome analyses were done in the intention-to-treat population. We assessed the treatment credibility and expectancy of the interventions and the two mechanisms (defence behaviours and safety beliefs) that the cognitive intervention was designed to target. This trial is prospectively registered with the ISRCTN registry, ISRCTN12497310. FINDINGS: From Sept 21, 2018, to May 13, 2021 (with a pause due to COVID-19 pandemic restrictions from March 16, 2020, to Sept 14, 2020), we recruited 80 participants with persistent persecutory delusions (49 [61%] men, 31 [39%] women, with a mean age of 40 years [SD 13, range 18-73], 64 [80%] White, six [8%] Black, one [1%] Indian, three [4%] Pakistani, and six [8%] other race or ethnicity). We randomly assigned 39 (49%) participants assigned to VR cognitive therapy and 41 (51%) participants to VR mental relaxation. 33 (85%) participants who were assigned to VR cognitive therapy attended all four sessions, and 35 (85%) participants assigned to VR mental relaxation attended all four sessions. We found no significant differences between the two VR interventions in participant ratings of treatment credibility (adjusted mean difference -1·55 [95% CI -3·68 to 0·58]; p=0·15) and outcome expectancy (-0·91 [-3·42 to 1·61]; p=0·47). 77 (96%) participants provided follow-up data at the primary timepoint. Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater improvement in persecutory delusions (adjusted mean difference -2·16 [-12·77 to 8·44]; p=0·69). Compared with VR mental relaxation, VR cognitive therapy did not lead to a greater reduction in use of defence behaviours (adjusted mean difference -0·71 [-4·21 to 2·79]; p=0·69) or a greater increase in belief in safety (-5·89 [-16·83 to 5·05]; p=0·29). There were 17 serious adverse events unrelated to the trial (ten events in seven participants in the VR cognitive therapy group and seven events in five participants in the VR mental relaxation group). INTERPRETATION: The two VR interventions performed similarly, despite the fact that they had been designed to affect different mechanisms. Both interventions had high uptake rates and were associated with large improvements in persecutory delusions but it cannot be determined that the treatments accounted for the change. Immersive technologies hold promise for the treatment of severe mental health problems. However, their use will likely benefit from experimental research on the application of different therapeutic techniques and the effects on a range of potential mechanisms of action. FUNDING: Medical Research Council Developmental Pathway Funding Scheme and National Institute for Health and Care Research Oxford Health Biomedical Research Centre.

Relationships between illness representations, physical activity and depression in chronic kidney disease.

BACKGROUND: Chronic Kidney Disease (CKD) is exacerbated by depression and confers significant healthcare costs. Whilst adverse impacts may be mitigated by physical activity, many patients with CKD remain physically inactive, with this physical inactivity potentially influenced by how CKD is appraised. OBJECTIVES: The study aims to explore the relationship between physical activity, depression and illness representations in CKD. METHODS: Patients with CKD but not requiring dialysis completed the Revised Illness Perception Questionnaire (IPQ-R), Beck Depression Inventory (BDI-II) and Short-Form International Physical Activity Questionnaire (IPAQ-SF). Demographic information was obtained via medical records. Correlation and regression analyses were conducted to determine the relationship of illness representations with levels of physical activity. Moderation and mediation analyses were performed to investigate the role of depression in any relationship between illness representations and physical activity levels. RESULTS: Seventy respondents, 60 % male, with a mean age of 60 ± 16 years, took part in the study. Of illness representation dimensions, personal control was positively associated with levels of physical activity whilst timeline cyclical (a subscale of the IPQ-R relating to patient beliefs about the nature of their illness) was a significant predictor. Severity of depression was neither a moderator nor a mediator of illness representations and levels of physical activity. CONCLUSION: Facets of illness representations had significant relationships with levels of physical activity. Future research concerning the development and validation of psychological interventions based on an illness representations framework for patients with CKD not requiring dialysis is proposed. The efficacy of such interventions could be then evaluated using a randomised controlled method.

Kidney symptom questionnaire: Development, content validation and relationship with quality of life.

BACKGROUND: Chronic kidney disease (CKD) is associated with a range of symptoms, even at early stages. The importance of patient symptom experience is increasingly recognised, but validated symptom scores are lacking. OBJECTIVES: This study aimed to refine an existing symptom questionnaire for use with patients not requiring renal replacement therapy (RRT), carry out content validity testing and explore convergent validity by comparing symptom scores with quality of life (QoL). DESIGN: A mixed-methods approach involving questionnaires, semi-structured interviews and a focus group. PARTICIPANTS: Patients with CKD not undergoing RRT and expert health professionals. APPROACH: Two hundred and nineteen patients completed an existing symptom questionnaire. The most commonly reported symptoms were identified, and descriptions refined in 11 semi-structured interviews. The questionnaire design was reviewed by a focus group. Content validity was established by a panel of expert health professionals. Seventy patients completed both the symptom questionnaire and a health-related QoL questionnaire (EQ-5D-5L). RESULTS: Thirteen common symptoms were identified. During the content validity phase, 13/16 experts responded (81%); 10/13 symptoms had 'excellent' or 'good' evaluation scores, and the content validity index of the whole questionnaire was 0.81, falling within the recommended threshold. Total symptom frequency scores, number of symptoms and the frequencies of 10/13 individual symptoms were all strongly associated with health-related QoL (EQ-5D-5L index score; p < 0.002 for all). CONCLUSION: This work has provided a new, validated symptom score for patients with CKD not requiring RRT for clinical management and research purposes.