The African, Caribbean and European (ACE) Pathways to Care study: A qualitative exploration of similarities and differences between African-origin, Caribbean-origin and European-origin groups in pathways to care for psychosis

Objectives: This paper reports on a qualitative exploration of the reasons for differences in pathways to care and duration of untreated psychosis (DUP) in the African, Caribbean and European (ACE) Pathways to Care study from the perspective of respondents to the study and their families. Setting: Ontario, Canada. Participants: Thirty-four participants in total. Twenty-five young people who had experienced a first episode of psychosis and nine family members. Participants were part of the ACE Pathways to Care study. Design: We implemented six focus groups. Furthermore, we implemented four in-depth interviews with two African-origin young women, one Caribbean-origin woman, and one European-origin woman with lived experience of psychosis. Results: Factors that influenced help-seeking delays across the three groups were: personal awareness of symptoms, family members\u27 knowledge of psychotic symptoms and knowledge of mental health services. Youth and their family members described how stigma played a key role in pathways to care by stopping them from asking for help. The way in which stigma operated on the three groups\u27 members, from feeling ashamed to feeling guilty for their mental illnesses, helped to explain differences in DUP between the groups. Guilt feelings emerged as a prominent theme among members from the African and Caribbean groups and it was not discussed in the European focus group. Delay in entering into first-episode psychosis programmes was also influenced by the stigma perceived by young people in healthcare settings. This had an impact on the therapeutic relationships, disclosure of symptoms and overall trust in the healthcare system. Conclusions: The findings of this paper suggest that stigma, especially internalised stigma, may operate in different ways in European-origin, African-origin and Caribbean-origin groups. These findings could inform the development of more equitable services for people in early stages of psychosis

Pathways to first-episode care for psychosis in African-, Caribbean-, and European-origin groups in Ontario

Objective: To compare the pathways to care and duration of untreated psychosis (DUP) for people of Black-African, Black-Caribbean, or White-European origin with first-episode psychosi(FEP). Methods: We recruited a sample of 171 patients with FEP of Black-African, Black-Caribbean, and White-European origin from hospital-and community-based early intervention services (EIS) in the cities of Toronto and Hamilton. We compared the 3 groups on DUP and key indicators of the pathway to care. Results: We observed differences in pathways to care across the 3 groups. Black-Caribbean participants had an increased odds of referral from an inpatient unit to EIS (OR 3.33; 95% CI 1.46 to 7.60) and a decreased odds of general practitioner involvement on the pathway to care (OR 0.17; 95% CI 0.07 to 0.46), as well as fewer total contacts (exp[β] 0.77; 95% CI 0.60 to 0.99) when compared with White-European participants. Black-African participants had an increased odds of contact with the emergency department at first contact (OR 3.78; 95% CI 1.31 to 10.92). The differences in the DUP between groups were not statistically significant. Conclusions: Our findings suggest that there are significant differences in the pathways to EIS for psychosis for people of African and Caribbean origin in our Canadian context. It is essential to gain a comprehensive understanding of the pathways that different population groups take to mental health services, and the reasons behind observed differences, to inform the development of equitable services, targeting patients in the critical early stages of psychotic disorder

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The Black Knight

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Systematic review of reviews of behavioural HIV prevention interventions among men who have sex with men

Men who have sex with men (MSM) remain one of the groups most at risk of HIV. The growing evidence-base on behavioural HIV prevention interventions includes systematic review-level evidence, including reviews specific to MSM populations. Here, we provide an up-to-date review of these systematic reviews in which we examined the effectiveness of behavioural HIV prevention interventions among MSM. A systematic search of electronic databases, including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, PsycInfo, from January 2000 to October 2010, along with hand searches of the reference lists of retrieved documents were conducted. Inclusion criteria included: study design limited to systematic reviews and meta-analyses; methodological quality; and review to focus on MSM and behavioural interventions. A narrative synthesis was conducted. Across the four included meta-analyses (102 studies; 52 independent studies), there was strong and consistent evidence for group- and community-level interventions being associated with reductions in UAI (27-30% and 30%, respectively) and increases in condom use amongst MSM, but inconsistent evidence for the effectiveness of individual-level interventions. Skills-building, trained professionals delivering the training and theory-based interventions were also consistently effective. The inherent limitations of the review of review method within a changing health domain meant it was difficult to develop contemporary and directly transferable guidance to HIV prevention policy development. However, the analysis does demonstrate a need for a step change in the kinds of data that are collated in the development of future systematic reviews of HIV prevention interventions among MSM

Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases.

Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here