Prevalence and nature of multi-sensory and multi-modal hallucinations in people with first episode psychosis

Hallucinations can occur in single or multiple sensory modalities. This study explored how common these experiences were in people with first episode of psychosis (n = 82). Particular attention was paid to the number of modalities reported and whether the experiences were seen to be linked temporally and thematically. It was predicted that those people reporting a greater number of hallucinations would report more delusional ideation, greater levels of distress generally and lower functioning. All participants reported hallucinations in the auditory domain, given the nature of the recruitment. The participants also reported a range of other unusual sensory experiences, with visual and tactile hallucinations being reported by over half. Moreover, single sensory experiences or unimodal hallucinations were less common than two or more hallucination modalities which was reported by 78% of the participants. The number of hallucinations was significantly associated with greater delusional ideation and higher levels of general distress, but not with reduced functioning. It is clear there is a need to refine psychological treatments so that they are better matched to the actual experiences reported by people with psychosis. Theoretical implications are also considered

Correction: Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum

Var genes encode the major surface antigen (PfEMP1) of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLalpha domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG) and 59 from widespread geographic origins (global). Overall, we obtained over 8,000 quality-controlled DBLalpha sequences. Within our sampling frame, the global population had a total of 895 distinct DBLalpha "types" and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLalpha types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes

Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): findings from an exploratory randomised controlled trial.

Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n=40) or TAU alone (n=42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment

Group cognitive rehabilitation to reduce the psychological impact of multiple sclerosis on quality of life: the CRAMMS RCT

AbstractBackgroundPeople with multiple sclerosis have problems with memory and attention. The effectiveness of cognitive rehabilitation has not been established.ObjectivesThe objectives were to assess the clinical effectiveness and cost-effectiveness of a cognitive rehabilitation programme for people with multiple sclerosis.DesignThis was a multicentre, randomised controlled trial in which participants were randomised in a ratio of 6 : 5 to receive cognitive rehabilitation plus usual care or usual care alone. Participants were assessed at 6 and 12 months after randomisation.SettingThe trial was set in hospital neurology clinics and community services.ParticipantsParticipants were people with multiple sclerosis who had cognitive problems, were aged 18–69 years, could travel to attend group sessions and gave informed consent.InterventionThe intervention was a group cognitive rehabilitation programme delivered weekly by an assistant psychologist to between four and six participants for 10 weeks.Main outcome measuresThe primary outcome was the Multiple Sclerosis Impact Scale – Psychological subscale at 12 months. Secondary outcomes included results from the Everyday Memory Questionnaire, the 30-Item General Health Questionnaire, the EuroQol-5 Dimensions, five-level version and a service use questionnaire from participants, and the Everyday Memory Questionnaire – relative version and the Modified Carer Strain Index from a relative or friend of the participant.ResultsOf the 449 participants randomised, 245 were allocated to cognitive rehabilitation (intervention group) and 204 were allocated to usual care (control group). Of these, 214 in the intervention group and 173 in the control group were included in the primary analysis. There was no clinically important difference in the Multiple Sclerosis Impact Scale – Psychological subscale score between the two groups at the 12-month follow-up (adjusted difference in means –0.6, 95% confidence interval –1.5 to 0.3; p = 0.20). There were no important differences between the groups in relation to cognitive abilities, fatigue, employment, or carer strain at follow-up. However, there were differences, although small, between the groups in the Multiple Sclerosis Impact Scale – Psychological subscale score at 6 months (adjusted difference in means –0.9, 95% confidence interval –1.7 to –0.1; p = 0.03) and in everyday memory on the Everyday Memory Questionnaire as reported by participants at 6 (adjusted difference in means –5.3, 95% confidence interval –8.7 to –1.9) and 12 months (adjusted difference in means –4.4, 95% confidence interval –7.8 to –0.9) and by relatives at 6 (adjusted difference in means –5.4, 95% confidence interval –9.1 to –1.7) and 12 months (adjusted difference in means –5.5, 95% confidence interval –9.6 to –1.5) in favour of the cognitive rehabilitation group. There were also differences in mood on the 30-Item General Health Questionnaire at 6 (adjusted difference in means –3.4, 95% confidence interval –5.9 to –0.8) and 12 months (adjusted difference in means –3.4, 95% confidence interval –6.2 to –0.6) in favour of the cognitive rehabilitation group. A qualitative analysis indicated perceived benefits of the intervention. There was no evidence of a difference in costs (adjusted difference in means –£574.93, 95% confidence interval –£1878.93 to £729.07) or quality-adjusted life-year gain (adjusted difference in means 0.00, 95% confidence interval –0.02 to 0.02). No safety concerns were raised and no deaths were reported

Promoting Independence in Dementia (PRIDE): protocol for a feasibility randomised controlled trial.

BACKGROUND: Memory services often see people with early stage dementia who are largely independent and able to participate in community activities but who run the risk of reducing activities and social networks. PRIDE is a self-management intervention designed to promote living well and enhance independence for people with mild dementia. This study aims to examine the feasibility of conducting a definitive randomised trial comparing the clinical and cost-effectiveness of the PRIDE intervention offered in addition to usual care or with usual care alone. METHODS/DESIGN: PRIDE is a parallel, two-arm, multicentre, feasibility, randomised controlled trial (RCT). Eligible participants aged 18 or over who have mild dementia (defined as a score of 0.5 or 1 on the Clinical Dementia Rating Scale) who can participate in the intervention and provide informed consent will be randomised (1:1) to treatment with the PRIDE intervention delivered in addition to usual care, or usual care only. Participants will be followed-up at 3 and 6 month's post-randomisation. There will be an option for a supporter to join each participant. Each supporter will be provided with questionnaires at baseline and follow-ups at 3 to 6 months. Embedded qualitative research with both participants and supporters will explore their perspectives on the intervention investigating a range of themes including acceptability and barriers and facilitators to delivery and participation. The feasibility of conducting a full RCT associated with participant recruitment and follow-up of both conditions, intervention delivery including the recruitment, training, retention of PRIDE trained facilitators, clinical outcomes, intervention and resource use costs and the acceptability of the intervention and study related procedures will be examined. DISCUSSION: This study will assess whether a definitive randomised trial comparing the clinical and cost-effectiveness of whether the PRIDE intervention offered in addition to usual care is feasible in comparison to usual care alone, and if so, will provide data to inform the design and conduct of a future trial. TRIAL REGISTRATION: ISRCTN, ISRCTN11288961, registered on 23 October 2019, http://www.isrctn.com/ISRCTN12345678 Protocol V2.1 dated 19 June 2019

Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum

Var genes encode the major surface antigen (PfEMP1) of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLα domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG) and 59 from widespread geographic origins (global). Overall, we obtained over 8,000 quality-controlled DBLα sequences. Within our sampling frame, the global population had a total of 895 distinct DBLα “types” and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLα types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes

The clinical and cost-effectiveness of rehabilitation of memory in brain injury: the ReMemBrIn RCT

Background People with traumatic brain injuries (TBIs) commonly report memory impairments. These are persistent, debilitating, and reduce quality of life, but patients do not routinely receive memory rehabilitation after discharge from hospital. Objectives To assess the clinical and cost-effectiveness of a group memory rehabilitation programme for people with TBI. Design Multi-centre, pragmatic, cluster randomised controlled trial. Qualitative and health economic evaluations were also undertaken. Setting Community settings in nine sites in England. Participants Participants were aged 18-69 years, with TBI more than 3 months prior to recruitment, reported memory problems, who were able to travel to a site to attend group sessions, communicate in English, and gave informed consent. Randomisation and blinding Clusters of 4 to 6 participants were randomised to intervention or control on a 1:1 ratio. Randomisation was based on a computer generated pseudo-random code using random permuted blocks of randomly varying size, stratified by study site. Participants and therapists were aware of the treatment allocation; outcome assessors were blinded. Interventions Ten weekly sessions of a manualised memory rehabilitation programme were provided in addition to usual care. Participants were taught restitution strategies to retrain impaired memory functions and compensation strategies to enable them to cope with memory problems. The control arm received usual care only. Outcomes Outcomes were assessed at 6 and 12 months after randomisation. Primary: Patient-completed Everyday Memory Questionnaire (EMQ-p) at 6-month follow-up. Secondary: Rivermead Behavioural Memory Test-3, General Health Questionnaire-30, European Brain Injury Questionnaire, Everyday Memory Questionnaire-relative version, individual goal attainment. Costs (based on a UK NHS and PSS perspective) were collected using a service use questionnaire, with the EQ-5D 5L used to derive Quality Adjusted Life Years. A Markov model was developed to explore cost-effectiveness at 5 and 10 years, with 3.5% discount applied. Results We randomised 328 participants (intervention: n=171; control: n=157), with 129 in the intervention arm and 122 in the control arm included in the primary analysis. We found no clinically important difference on the EMQ-p between the two arms at 6-month follow-up (adjusted difference in means -2.1, 95% CI -6.7 to 2.5, p=0.37). For secondary outcomes, differences favouring the intervention arm were observed at 6-month follow-up for RBMT and goal attainment, but remained only for goal attainment at 12-month follow-up. There were no differences between arms in mood or quality of life. Qualitative results suggested positive experiences of participating in the trial and of attending the groups. Participants reported that memory rehabilitation was not routinely accessible in usual care. The primary health economics outcome at 12-months found memory rehabilitation to be £26.89 cheaper than usual care but less effective with an incremental QALY loss of 0.007. Differences in costs and effects were not statistically significant and non-parametric bootstrapping demonstrated considerable uncertainty in these findings. No safety concerns were raised and no deaths reported. Limitations As a pragmatic trial, we had broad inclusion criteria, therefore there was considerable heterogeneity within the sample. The study was not powered to perform further sub-group analyses. Participants and therapists could not be blinded to treatment allocation. Conclusions The group memory rehabilitation delivered in this trial is very unlikely to lead to clinical benefits or to be a cost-effective treatment for people with TBI in the community. Future work Future studies should examine the inclusion and selection of participants who may benefit most from memory rehabilitation. Registration ISRCTN65792154 Funding National Institute for Health Research, Health Technology Assessmen

Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Cognitive rehabilitation for attention and memory in people with multiple sclerosis: a randomized controlled trial (CRAMMS)

Objective: To assess the clinical and cost-effectiveness of cognitive rehabilitation for attention and memory problems in people with multiple sclerosis. Design: Multicentre, pragmatic, randomized controlled trial. Setting: Community Participants: People with multiple sclerosis aged 18–69 years, who reported cognitive problems in daily life and had cognitive problems on standardized assessment. Interventions: A group cognitive rehabilitation programme delivered in 10 weekly sessions in comparison with usual care. Main measures: The primary outcome was the Multiple Sclerosis Impact Scale Psychological subscale at 12 months after randomization. Secondary outcomes included measures of everyday memory problems, mood, fatigue, cognitive abilities and employment at 6 and 12 months after randomization. Results: In all, 245 participants were allocated to cognitive rehabilitation and 204 to usual care. Mean Multiple Sclerosis Impact Scale Psychological at 12 months was 22.2 (SD = 6.1) for cognitive rehabilitation and 23.4 (SD = 6.0) for usual care group; adjusted difference −0.6, 95% confidence interval (CI) = −1.5 to 0.3, P = 0.20. No differences were observed in cognitive abilities, fatigue or employment. There were small differences in favour of cognitive rehabilitation for the Multiple Sclerosis Impact Scale Psychological at 6 months and everyday memory and mood at 6 and 12 months. There was no evidence of an effect on costs (−£808; 95% CI = −£2248 to £632) or on quality-adjusted life year gain (0.00; 95% CI = −0.01 to 0.02). Conclusion: This rehabilitation programme had no long-term benefits on the impact of multiple sclerosis on quality of life, but there was some evidence of an effect on everyday memory problems and mood

Eye Tricks

Catalog for the exhibition Eye Tricks held at the Seton Hall University Walsh Gallery, November 12 - December 15, 2007. Curated by Jeanne Brasile and Jason Marquis. Includes the essay Illusion / Elusion by Jason Marquis. Includes color illustrations