Real-time data monitoring for ulcerative colitis: patient perception and qualitative analysis.

BACKGROUND/AIMS: TrueColours ulcerative colitis (TCUC) is a comprehensive web-based program that functions through email, providing direct links to questionnaires. Several similar programs are available, however patient perspectives are unexplored. METHODS: A pilot study was conducted to determine feasibility, usability and patient perceptions of real-time data collection (daily symptoms, fortnightly quality of life, 3 monthly outcomes). TCUC was adapted from a web-based program for patients with relapsing-remitting bipolar disorder, using validated UC indices. A semi-structured interview was developed and audio-recorded face-to-face interviews were conducted after 6 months of interaction with TCUC. Transcripts were coded in NVivo11, a qualitative data analysis software package. An inductive approach and thematic analysis was conducted. RESULTS: TCUC was piloted in 66 patients for 6 months. Qualitative analysis currently defies statistical appraisal beyond "data saturation," even if it has more influence on clinical practice than quantitative data. A total of 28 face-to-face interviews were conducted. Six core themes emerged: awareness, control, decision-making, reassurance, communication and burden of treatment. There was a transcending overarching theme of patient empowerment, which cut across all aspects of the TCUC experience. CONCLUSIONS: Patient perception of the impact of real-time data collection was extremely positive. Patients felt empowered as a product of the self-monitoring format of TCUC, which may be a way of improving self-management of UC whilst also decreasing the burden on the individual and healthcare services.

The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS): study protocol for a randomised controlled, experimental medicine study.

BACKGROUND: The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour. METHODS: The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737. DISCUSSION: The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected. TRIAL REGISTRATION: ISRCTN, ISRCTN33631053 . Retrospectively registered on 8 June 2018 (applied 17 May 2018).

Defining Faecal Calprotectin Thresholds as a Surrogate for Endoscopic and Histological Disease Activity in Ulcerative Colitis-a Prospective Analysis.

BACKGROUND: Faecal calprotectin [FCal] levels are used as a surrogate marker for mucosal inflammation, but thresholds for defining endoscopic or histological disease activity in ulcerative colitis [UC] remain unclear. METHODS: Using validated indices, prospective measurements of FCal, symptoms [Simple Colitis Clinical Activity Index, SCCAI], endoscopic [Ulcerative Colitis Endoscopic Index of Severity, UCEIS] and histological activity [Nancy index] were made over 6 months in patients enrolled into the TrueColours UC web-based monitoring programme. Repeated measurements correlation was performed between FCal and SCCAI, UCEIS, and Nancy indices using definitions for remission and active disease [UCEIS: remission ≤1, active ≥4; Nancy: remission ≤1, active ≥2; combined criteria: remission UCEIS ≤1 and Nancy ≤1, active UCEIS ≥4 and Nancy ≥2]. Receiver operating characteristic curves investigated FCal thresholds after maximising sensitivity for active disease. RESULTS: In 39 patients followed prospectively for 6 months, correlation coefficients between FCal and SCCAI, UCEIS, and Nancy indices were 0.271 (95% confidence interval [CI] 0.114-0.415), 0.741 [95% CI 0.289-0.922], and 0.876 [95% CI 0.605-0.965], respectively. Median FCal thresholds for remission using endoscopic, histological, or combined criteria were 71 µg/g [range 8-624], 91 µg/g [range 8-858], and 67 µg/g [range 8-479], respectively. The FCal threshold above which active disease was confirmed was 187 µg/g for UCEIS (area under the curve [AUC] 0.915), 72 µg/g for Nancy [AUC 0.824], and 187 µg/g for combined endoscopic and histological criteria [AUC 0.936]. CONCLUSIONS: Correlation between FCal and symptoms in UC is weak. In contrast, the correlation between FCal and endoscopic or histological activity is strong. An FCal ≥72 µg/g indicates histological inflammation [Nancy ≥2] and ≥187 µg/g indicates endoscopically active disease [UCEIS ≥4], whether combined with histopathology or not.

The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis.

BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust.

Longitudinal mood monitoring in bipolar disorder: Course of illness as revealed through a short messaging service.

BACKGROUND: Online self-monitoring of mood can be used to investigate differences in course patterns across patient groups. This study explored the feasibility of remote symptom capture with True Colours, a self-rated online mood monitoring tool completed on a weekly basis. METHODS: Participants with bipolar disorder (N = 297) completed weekly depression and mania questionnaires over an average of 27.5 months (range 1 -81 months). Subgroups defined by sex, age, and bipolar I vs. II status were compared on time in various mood states, number of episodes, and week-to-week mood variability. RESULTS: Compliance with weekly questionnaires was generally high (median, 92% of weeks). Mood symptoms occurred for an average of 55.4% of weeks across the follow-up period. Females spent more time with hypomanic/manic and depressive symptoms and had more depressive episodes compared to males. Younger participants were found to experience more hypomanic/manic episodes and showed greater variability in mood symptoms than older participants. No significant differences in mood symptoms or variability were observed between bipolar I and II patients. LIMITATIONS: This was a naturalistic study with a heterogeneous cohort, and did not include a control group. True Colours does not identify mood fluctuations that may occur in the days between weekly assessments. CONCLUSIONS: Monitoring moods through an online tool is both feasible and informative regarding course of illness in patients with bipolar disorder. Interventions aiming to reduce mood variability and manic/hypomanic episodes in the early phases of bipolar disorder may enhance the long-term symptomatic course of the illness.

Web-Based Violence Risk Monitoring Tool in Psychoses: Pilot Study in Community Forensic Patients.

We describe the development and pilot testing of a novel, web-based, violence risk monitoring instrument for use in community patients with psychoses. We describe the development of the tool, including drawing on systematic reviews of the field, how item content was operationalized, the development of a user interface, and its subsequent piloting. Sixty-eight patients were included from three English counties, who had been discharged from forensic psychiatric services. Over 12 months, 310 questionnaires were completed on the sample by professionals from several disciplines and qualitative feedback collected relating to the use of the tool using an electronic survey. Strengths of this approach for risk assessment, and potential limitations and areas for future research, are discussed.

Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): a 2 × 2 factorial randomised trial.

BACKGROUND: Depressive symptoms are a major cause of disability in bipolar disorder and there are few safe and effective treatments. The combination of lamotrigine plus quetiapine potentially offers improved outcomes for people with bipolar depression. We aimed to determine if combination therapy with quetiapine plus lamotrigine leads to greater improvement in depressive symptoms over 12 weeks than quetiapine monotherapy plus lamotrigine placebo. METHODS: In this double-blind, randomised, placebo-controlled, parallel group, 2 × 2 factorial trial (CEQUEL), patients with DSM-IV bipolar disorder I or II, who were aged 16 years or older, and required new treatment for a depressive episode, were enrolled from 27 sites in the UK. Patients were randomly assigned (1:1) by an adaptive minimisation algorithm to lamotrigine or placebo and to folic acid or placebo. Participants and investigators were masked to the treatment groups. The primary outcome was improvement in depressive symptoms at 12 weeks with the Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16). Analysis was by modified intention-to-treat. This trial is registered with EUdraCT, number 2007-004513-33. FINDINGS: Between Oct 21, 2008, and April 27, 2012, 202 participants were randomly assigned; 101 to lamotrigine and 101 to placebo. The mean difference in QIDS-SR16 total score between the group receiving lamotrigine versus the placebo group at 12 weeks was -1·73 ([95% CI -3·57 to 0·11]; p=0·066) and at 52 weeks was -2·69 ([-4·89 to -0·49]; p=0·017). Folic acid was not superior to placebo. There was a significant interaction (p=0·028), with folic acid reducing the effectiveness of lamotrigine at 12 weeks. The mean difference on QIDS-SR16 was -4·14 ([95% CI -6·90 to -1·37]; p=0·004) for patients receiving lamotrigine without folic acid compared with 0·12 ([-2·58 to 2·82]; p=0·931) for those receiving lamotrigine and folic acid. INTERPRETATION: Addition of lamotrigine to quetiapine treatment improved outcomes. Folic acid seems to nullify the effect of lamotrigine. CEQUEL should encourage clinicians and patients to consider lamotrigine for bipolar depression, but also to be aware that concurrent folic acid might reduce its effectiveness. FUNDING: Medical Research Council.

Effects of cognitive behavioural therapy for insomnia on the mental health of university students: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia, defined as repeated difficulties getting or staying asleep, is common in the general population. Such sleep difficulties are a problem in their own right, but increasingly it is being recognised that they may also be a contributory factor in the development of a wide range of mental health problems. Our focus is upon the relationship between insomnia and psychotic experiences, such as paranoia and hallucinations. Psychotic experiences commonly occur in mild forms in the general population and have been linked to disrupted sleep. These psychotic-like experiences raise the risk of development of a clinical disorder. Our aim is to reduce insomnia in a large general population group, and examine the effect on paranoia and hallucinations at the age when mental health problems typically emerge. The primary hypotheses are that cognitive behaviour therapy (CBT) for insomnia will reduce insomnia and also levels of paranoia and hallucinations. The theoretical links will be substantiated by a planned mediation analysis. Improvements in a number of other mental health outcomes are also predicted. METHODS/DESIGN: We will carry out a parallel group, randomised controlled trial of 2,614 students with insomnia in universities across the UK. In the Oxford Access for Students Improving Sleep (OASIS) trial, participants will be randomised to digital CBT for insomnia (in addition to treatment as usual) or treatment as usual. Online assessments will take place at zero, three, 10 (post-treatment), and 22 (follow-up) weeks. Primary outcomes are insomnia and psychotic-like experiences (paranoia or hallucinatory experiences) at 10 weeks. Secondary outcomes are levels of mania, depression, anxiety, nightmares, psychological wellbeing, and the development of mental health disorders. All main analyses will be carried out at the end of the last follow-up assessment and will be based on the intention-to-treat principle. The trial is funded by the Wellcome Trust. DISCUSSION: This study will be the first large-scale causal test of the relationship between sleep disturbance and psychotic experiences. It will provide evidence concerning the clinical effects of treating insomnia in young adults. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN61272251 ) on 29 January 2015.