Addressing the need for Indigenous-specific PROMs and PREMS: A focus on methodology.

PURPOSE: Differences in Indigenous worldviews, practices and values highlight the need for Indigenous-specific health quality indicators, such as patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). The purpose of this paper is to present our methodology, as part of a larger study that sought to develop a framework for creating Indigenous-specific PROMs and PREMs. METHODS: The research design was informed by Indigenous research methodology and a community-based participatory approach. It had three core components: (1) a literature exploration of existing Indigenous-specific PROMs and PREMs; (2) interviews with researchers with expertise in PROMs and PREMs developed for Indigenous populations and community leaders interested in using these Indigenous-informed evaluation tools; and (3) conversations with Indigenous community members about their experiences with health surveys. Interviews were audio-recorded and transcribed verbatim; transcripts were analyzed qualitatively using an inductive and deductive approach. Themes and sub-themes were identified to build a framework that honours Indigenous knowledges and ways of knowing. Results were validated with select research participants and the Project Advisory Committee. RESULTS: Findings demonstrate how relationship building is the necessary starting point for engagement when developing survey instruments with Indigenous peoples. Engagement requires respectful collaboration through all stages of the project from determining what questions are asked to how the information will be collected, interpreted, and managed. A relational stance requires responsibility to Indigenous communities and peoples that goes beyond research carried out using a western scientific lens. It means ensuring that the project is beneficial to the community and framing questions based on Indigenous knowledge, worldviews, and community involvement. CONCLUSIONS: This study employed a collaborative, participatory qualitative approach to develop a framework for creating PROMs and PREMs with Indigenous peoples. The methods described offer concrete examples of strategies that can be employed to support relationship-building and collaboration when developing Indigenous-specific survey instruments.

Pathways: A guide for developing culturally safe and appropriate patient-reported outcome (PROMs) and experience measures (PREMs) with Indigenous peoples.

BACKGROUND: Members of the Indigenous Health Program, BC Children's and Women's Hospitals and the University of British Columbia embarked on a joint project to describe best practices to support the creation of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) with Indigenous peoples. METHODS: The project involved a review of previous research on patient-reported measures (surveys) that had been specifically developed for Indigenous populations. It also involved interviews with key stakeholders-Indigenous and non-Indigenous academic researchers, and Indigenous community leaders and community members. Themes from the interviews and the literature review were combined and synthesized into pathways/a framework for survey development. RESULTS: The pathways document consisted of 13 protocols and associated teachings for guiding processes and framing survey questions. These encompassed building relationships, community engagement and consultation, benefits to community, ceremony and storytelling, two-way learning, participatory content development, governance and accountability. Findings emphasized the criticality of Indigenous leadership in setting priorities for PROMs and PREMS and establishing relationships that honour Indigenous experiences through all phases of a study. Assessment of the framework's validity with select research participants and the Project Advisory Committee was positive. CONCLUSION: This is the first framework to guide development of PROMs and PREMs with Indigenous peoples and communities. It addresess both process and outcome and includes concrete steps that collaborators can take when establishing a partnership that is respectful and inclusive of Indigenous ways of knowing and being.

Breast Cancer Germline Genetic Counseling and Testing for Populations of African Heritage Globally: A Scoping Review on Research, Practice, and Bioethical Considerations.

PURPOSE: Despite the disproportionately high risk of breast cancer among women of African heritage, little is known about the facilitators and barriers to implementing germline genetic testing and counseling (GT/C). METHODS: This scoping review followed guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Published manuscripts from database inception through 2021 were sourced from PubMed, Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase, Cochrane Library, and Scopus. Search terms were used to retrieve articles addressing (1) African heritage, (2) breast cancer, and (3) GT or GC. The screening involved abstract and title review and full-text review. Data were extracted for all articles meeting the inclusion criteria. RESULTS: A total of 154 studies were included. Most studies that took place were conducted in the United States (71.4%), and most first authors (76.9%) were from the United States. GT was conducted in 73 (49.7%) studies. BRCA1/BRCA2 were the most commonly studied genes for germline mutations. GC was conducted in 49 studies (33.3%), and perspectives on GC were evaluated in 43 (29.3%). The use of racial/ethnic categories varied broadly, although African American was most common (40.1%). Racism was mentioned in three studies (2.0%). CONCLUSION: There is a growing body of literature on GT/C for breast cancer in women of African heritage. Future studies on GT/C of African populations should consider increased clarity around racial/ethnic categorizations, continued community engagement, and intentional processes for informed consent.

Active Q-Switched X-Ray Regenerative Amplifier Free-Electron Laser.

Despite tremendous progress in x-ray free-electron laser (FEL) science over the last decade, future applications still demand fully coherent, stable x rays that have not been demonstrated in existing x-ray FEL facilities. In this Letter, we describe an active Q-switched x-ray regenerative amplifier FEL scheme to produce fully coherent, high-brightness, hard x rays at a high-repetition rate. By using simple electron-beam phase space manipulation, we show this scheme is flexible in controlling the x-ray cavity quality factor Q and hence the output radiation. We report both theoretical and numerical studies on this scheme with a wide range of accelerator, x-ray cavity, and undulator parameters.

Indigenous Peoples and genomics: Starting a conversation.

Compared to European ancestral groups, Indigenous Canadians are more likely to have uninterpretable genome-wide sequencing results due to non-representation in reference databases. We began a conversation with Indigenous Canadians to raise awareness and give voice to this issue. We co-created a video explaining genomic non-representation that included diverse Indigenous view-points. We audio-recorded the focus groups including 30 First Nations, Métis, and Inuit individuals living in Greater Vancouver. After watching an introductory video explaining genomic testing, participants discussed issues surrounding collecting Indigenous genomic data, its control, and usage. Transcripts were analyzed, and participants' quotes representing main themes were incorporated into the introductory video. Indigenous participants discussed data interpretation and gave approval for quote usage. The 20 participants who provided feedback concurred with the thematic interpretation: Systemic racism interlaced most conversations, particularly within the theme of trust. Themes of governance emphasized privacy and fear of discrimination. Some participants thought a separate, Indigenous-controlled database was essential; others recognized advantages of international databases. The theme of implementation included creative ideas to collect Indigenous genomes, but prior approval from Indigenous leaders was emphasized. The final video (https://youtu.be/-wivIBDjoi8) was shared with participants to use as they wish to promote awareness and ongoing discussion of genomic diagnostic inequity.

Evaluation of learning from Practical Obstetric Multi-Professional Training and its impact on patient outcomes in Australia using Kirkpatrick's framework: a mixed methods study.

OBJECTIVES: The aim of this study was to evaluate the implementation of the Practical Obstetric Multi-Professional Training (PROMPT) simulation using the Kirkpatrick's framework. We explored participants' acquisition of knowledge and skills, its impact on clinical outcomes and organisational change to integrate the PROMPT programme as a credentialing tool. We also aimed to assess participants' perception of usefulness of PROMPT in their clinical practice. STUDY DESIGN: Mixed methods approach with a pre-test/post-test design. SETTING: Healthcare network providing obstetric care in Victoria, Australia. PARTICIPANTS: Medical and midwifery staff attending PROMPT between 2013 and 2015 (n=508); clinical outcomes were evaluated in two cohorts: 2011-2012 (n=15 361 births) and 2014-2015 (n=12 388 births). INTERVENTION: Attendance of the PROMPT programme, a simulation programme taught in multidisciplinary teams to facilitate teaching emergency obstetric skills. MAIN OUTCOME MEASURE: Clinical outcomes compared before and after embedding PROMPT in educational practice. SECONDARY OUTCOME MEASURE: Assessment of knowledge gained by participants through a qualitative analysis and description of process of embedding PROMPT in educational practice. RESULTS: There was a change in the management of postpartum haemorrhage by early recognition and intervention. The key learning themes described by participants were being prepared with a prior understanding of procedures and equipment, communication, leadership and learning in a safe, supportive environment. Participants reported a positive learning experience and increase in confidence in managing emergency obstetric situations through the PROMPT programme, which was perceived as a realistic demonstration of the emergencies. CONCLUSION: Participants reported an improvement of both clinical and non-technical skills highlighting principles of teamwork, communication, leadership and prioritisation in an emergency situation. An improvement was observed in management of postpartum haemorrhage, but no significant change was noted in clinical outcomes over a 2-year period after PROMPT. However, the skills acquired by medical and midwifery staff justify embedding PROMPT in educational programmes.

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia.

BACKGROUND: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. METHODS: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. RESULTS: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. CONCLUSION: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.

Failure to confirm genetic association between schizophrenia and markers on chromosome 1q23.3 in the region of the gene encoding the regulator of G-protein signaling 4 protein (RGS4).

The chromosome 1q23.3 region, which includes the RGS4 gene has been implicated in genetic susceptibility to schizophrenia by two linkage studies with lod scores of 6.35 and 3.20 and with positive lod between 2.00 and 3.00 scores in several other studies. Reduced post mortem RGS4 gene expression in the brain of schizophrenics was reported as well as positive allelic association between markers at the RGS4 gene locus and schizophrenia. We have attempted to replicate the finding of allelic association with schizophrenia in a UK based sample of 450 subjects with schizophrenia and 450 supernormal controls. We genotyped the same SNP marker alleles investigated in the earlier studies and also a di-nucleotide (GT)14 repeat microsatellite marker, which was 7 kb distal to RGS4. In the new UK sample there was no evidence for allelic or haplotypic association between RGS4 markers and schizophrenia. This might reflect genetic heterogeneity between the population samples, genotyping or other methodological problems. The finding weakens the evidence that mutations or variation in the RGS4 gene have an effect on schizophrenia susceptibility.

Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample.

BACKGROUND: Linkage studies have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. It was then claimed that markers at the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) gene showed allelic association with schizophrenia in Canadian families. A second Chinese study found a base pair polymorphism at the CAPON gene also associated with schizophrenia. METHODS: We attempted replication using eight markers from the Canadian study in a UK based sample of 450 cases and 450 supernormal controls. RESULTS: We found no evidence for allelic or haplotypic association with schizophrenia for any of the markers found to be associated in the Canadian sample. CONCLUSIONS: The negative results might reflect genetic heterogeneity between the Canadian, Chinese and UK samples or be due to methodological problems. The present finding weakens the evidence that mutations or variation in the CAPON gene are causing genetic susceptibility to schizophrenia in European populations.

The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia.

Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5' end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P=.01) and AAAT11 (P=.009), and two single-nucleotide-polymorphism markers within the Epsin 4 gene, rs10046055 (P=.007) and rs254664 (P=.01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P=.004; HapB, P=.0005; HapC, P=.007; and HapD, P=.01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3.

Self-reported suicidal behavior in juvenile offenders in custody: prevalence and associated factors.

Suicide rates in prisons in England and Wales are high, including those in juvenile detention centers. Previous deliberate self-harm (DSH) is the strongest predictor of suicide in the general population. There is limited information on how many juvenile offenders (15 to 18 year-olds) have a history of DSH at the time of entering custody, or on factors associated with previous DSH. We aimed to determine the prevalence of previous DSH and suicidal ideation in a population of juvenile offenders in custody and to identify factors associated with DSH and suicidal ideation. Seven out of 45 subjects (15.6%) reported an act of DSH in the past. Twelve (26.6%) reported past suicidal ideation. Peer relationship difficulties and sexual abuse were significantly associated with DSH (p < 0.05). Other factors showed a trend toward being more common among those with DSH, but the premature ending of the project by the juvenile detention center prevented full investigation of the extent of DSH and associated factors. Nevertheless, the results indicated a much higher rate of DSH in this population than in young males in the community. A larger joint project with juvenile detention centers is required to confirm the extent of previous DSH at the time young offenders are admitted, and the associated risk factors, in order to assist prevention and intervention strategies.