Accelerating the development of a psychological intervention to restore treatment decision-making capacity in patients with schizophrenia-spectrum disorder: a study protocol for a multi-site, assessor-blinded, pilot Umbrella trial (the DEC:IDES trial).

BACKGROUND: A high proportion of patients diagnosed with schizophrenia-spectrum disorders will at some point in their lives be assessed as not having the capacity to make their own decisions about pharmacological treatment or inpatient care ('capacity'). Few will be helped to regain it before these interventions proceed. This is partly because effective and safe methods to do so are lacking. Our aim is to accelerate their development by testing, for the first time in mental healthcare, the feasibility, acceptability and safety of running an 'Umbrella' trial. This involves running, concurrently and under one multi-site infrastructure, multiple assessor-blind randomised controlled trials, each of which is designed to examine the effect on capacity of improving a single psychological mechanism ('mechanism'). Our primary objectives are to demonstrate feasibility of (i) recruitment and (ii) data retention on the MacArthur Competence Assessment Tool-Treatment (MacCAT-T; planned primary outcome for a future trial) at end-of-treatment. We selected three mechanisms to test: 'self-stigma', low self-esteem and the 'jumping to conclusions' bias. Each is highly prevalent in psychosis, responsive to psychological intervention, and hypothesised to contribute to impaired capacity. METHODS: Sixty participants with schizophrenia-spectrum diagnoses, impaired capacity and one or more mechanism(s) will be recruited from outpatient and inpatient mental health services in three UK sites (Lothian, Scotland; Lancashire and Pennine; North West England). Those lacking capacity to consent to research could take part if the key criteria were met, including either proxy consent (Scotland) or favourable Consultee advice (England). They will be allocated to one of three randomised controlled trials, depending on which mechanism(s) they have. They will then be randomised to receive, over an 8-week period and in addition to treatment as usual (TAU), 6 sessions of either a psychological intervention which targets the mechanism, or 6 sessions of assessment of the causes of their incapacity (control condition). Participants are assessed at 0 (baseline), 8 (end-of-treatment) and 24 (follow-up) weeks post-randomisation using measures of capacity (MacCAT-T), mechanism, adverse events, psychotic symptoms, subjective recovery, quality of life, service use, anxiety, core schemata and depression. Two nested qualitative studies will be conducted; one to understand participant and clinician experiences and one to investigate the validity of MacCAT-T appreciation ratings. DISCUSSION: This will be the first Umbrella trial in mental healthcare. It will produce the first 3 single-blind randomised controlled trials of psychological interventions to support treatment decision-making in schizophrenia-spectrum disorder. Demonstrating feasibility will have significant implications not only for those seeking to support capacity in psychosis, but also for those who wish to accelerate the development of psychological interventions for other conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309435 . Pre-registered on 16 March 2020.

Exploratory RCT of a group psychological intervention for postnatal depression in British mothers of South Asian origin - ROSHNI-D.

BACKGROUND: Postnatal depression (PND) is a global public health problem. There is a high prevalence of PND amongst ethnic minority women and major ethnic inequalities in mental health care in the U.K. Language and cultural barriers pose a significant challenge for access to timely treatment and interventions for British South Asian (BSA) women with PND. METHODS: The study, carried out in Manchester and Lancashire, England, was a two-arm single-blind exploratory randomised controlled trial. BSA women (N = 83) having a baby <12 months were randomised either to the group receiving the culturally adapted Positive Health Programme (PHP) (n = 42) or to the group receiving treatment as usual (TAU) (n = 41). Follow-up assessments were at 3 months (end of intervention) and 6 months after randomisation. RESULTS: Using an intention to treat analysis, there was no significant difference between PHP intervention and TAU groups in depression measured using Hamilton Depression Rating Scale both at 3 and 6 months follow up. Using modified intention to treat analysis, women who attended four or more sessions showed significant reduction in depression in the PHP group compared to the TAU group and the greater number of sessions attended was associated with greater reductions in depression scores. LIMITATIONS: The sample was relatively small and the study was conducted in one geographical area in Northwest England; hence, these results may not be generalizable to other regions and populations. CONCLUSION: The recruitment and trial retention figures highlighted the ability of the research team to engage with BSA women, having implications in planning services for this group. TRIAL REGISTRATION: Clinicaltrials.govNCT01838889.

PAR1-dependent and independent increases in COX-2 and PGE2 in human colonic myofibroblasts stimulated by thrombin.

Subepithelial myofibroblast-derived prostaglandin E(2) (PGE(2)) regulates epithelial chloride secretion in the intestine. Thrombin is elevated in inflammatory conditions of the bowel. Therefore, we sought to determine a role for thrombin in regulating PGE(2) synthesis by colonic myofibroblasts. Incubation of cultured CCD-18Co colonic myofibroblasts with thrombin, the proteinase-activated receptor 1 (PAR(1))-activating peptide (Cit-NH(2)), and peptides corresponding to 2 noncatalytic regions of thrombin (TP367 and TP508) for 18 h increased both cyclooxygenase (COX)-2 expression (immunocytochemistry) and PGE(2) synthesis (enzyme immunoassay). Inhibition of thrombin by D-Phe-Pro-Arg-chloromethylketone (PPACK) did not significantly reduce PGE(2) synthesis, which remained elevated compared with control. We also investigated the basic fibroblast growth factor (bFGF) dependence of thrombin-induced PGE(2) elevations. Recombinant human bFGF concentration dependently increased PGE(2) synthesis, and a bFGF neutralizing antibody inhibited PGE(2) synthesis induced by TP367 and TP508 (approximately 40%) and by thrombin (approximately 20%) (but not Cit-NH(2)). Thrombin, therefore, upregulates COX-2-derived PGE(2) synthesis by both catalytic cleavage of PAR(1) and bFGF-dependent noncatalytic activity. This presents a novel mechanism by which intestinal myofibroblasts might regulate epithelial chloride secretion.