"Putting the power back into community": A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia's Northern Territory.

BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.

Workforce survey of PAs' genetic-genomic knowledge, attitudes, and application in practice.

OBJECTIVE: This study surveyed practicing physician associates/assistants (PAs) about their genetics-genomics knowledge, attitudes, and application in practice. METHODS: A 25-question electronic survey was emailed to each constituent organization of the American Academy of Physician Associates (AAPA) with a description of the study and a request to forward to their members. Additionally, a posting was displayed in the bulletin board section of the online AAPA Huddle. RESULTS: Of the 420 PAs who completed the survey, few are knowledgeable (25%) about or confident (13%) in applying a genomic approach to patient care, although most (61%) think genetics-genomics is important to delivering high-quality care. Remarkably, 97% of PAs surveyed are interested in genetics-genomics continuing medical education. CONCLUSIONS: PAs lack knowledge and confidence in integrating genetics-genomics into patient care; however, they have a positive attitude toward genetics-genomics and want to improve their knowledge and confidence through education.

The State of Genetics and Genomics Education in US Physician Assistant Programs.

PURPOSE: This study aimed to assess the current landscape of genetics-genomics education in physician assistant (PA) student training. METHODS: A 25-question electronic survey was emailed to program directors of the 273 accredited PA programs. Questions represented PA program demographics and 4 domains: curricular characteristics and perceived adequacy; content; curricular approaches and instructional methods; and intent, barriers, and perceived needs for an optimal curriculum. RESULTS: A total of 115 PA program representatives (42%) returned the survey. More than two-thirds of responding programs do not require a prerequisite genetics course for matriculation. Most programs (48%) include 1 to 10 contact hours of genetics-genomics content and use various content delivery methods and approaches. Most programs (67%) use PA program faculty to teach genetics-genomics as part of one course or many courses throughout the curriculum (85%) using didactic lectures (97%). The most significant barrier to developing an optimal curriculum is an already overloaded curriculum (71%). Physician assistant educators welcome supportive resources, such as genetic case studies (96%). CONCLUSIONS: The study findings elucidate the current state of genetics-genomics education in PA programs. Every responding program reports that genetics-genomics is integrated into their curriculum; however, no standardization exists between programs. Although medical genetics-genomics has changed and advanced rapidly since a similar survey was conducted 14 years ago, the number of contact hours is unchanged, and genetics-genomics content is less dispersed throughout PA curricula. To create genetic-competent and genomic-competent PAs, education must evolve to stay current with ongoing advancements in genomic science.

A Critical Review of the Prognostic and Predictive Implications of KRAS and STK11 Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent KRAS and STK11 mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of KRAS mutations, STK11 mutations, or KRAS/STK11 co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, KRAS mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. KRAS mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that STK11 mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, KRAS/STK11 co-mutations may predict primary resistance to ICI. Prospective KRAS/STK11-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published KRAS analyses are retrospective and hypothesis-generating in nature.

Sleep disturbances in Phelan-McDermid syndrome: Clinical and metabolic profiling of 56 individuals.

Phelan-McDermid Syndrome (PMS) is caused by deletions at chromosome 22q13.3 or pathogenic/likely pathogenic SHANK3 variants. The clinical presentation is extremely variable and includes global developmental delay/intellectual disability (ID), seizures, neonatal hypotonia, and sleep disturbances, among others. This study investigated the prevalence of sleep disturbances, and the genetic and metabolic features associated with them, in a cohort of 56 individuals with PMS. Sleep data were collected via standardized observer/caregiver questionnaires, while genetic data from array-CGH and sequencing of 9 candidate genes within the 22q13.3 region, and metabolic profiling utilized the Biolog Phenotype Mammalian MicroArray plates. Sleep disturbances were present in 64.3% of individuals with PMS, with the most common problem being waking during the night (39%). Sleep disturbances were more prevalent in individuals with a SHANK3 pathogenic variant (89%) compared to subjects with 22q13.3 deletions of any size (59.6%). Distinct metabolic profiles for individuals with PMS with and without sleep disturbances were also identified. These data are helpful information for recognizing and managing sleep disturbances in individuals with PMS, outlining the main candidate gene for this neurological manifestation, and highlighting potential biomarkers for early identification of at-risk subjects and molecular targets for novel treatment approaches.

Genetics and Genomics Education for Physician Assistant Students: A Review of the Literature.

INTRODUCTION: The purpose of this study was to critically review the literature and determine what is known about genetics-genomics education for physician assistants (PAs). METHODS: A rapid review method was used to search CINAHL, MEDLINE, PubMed, and Web of Science databases. The review is presented historically to describe the development of genetics-genomics education in PA programs. RESULTS: Of 594 publications retrieved, 11 articles met inclusion criteria. Retained articles include an assessment of PA programs, genetics-genomics competencies, educational efforts developed by PA programs regarding genetics-genomics, and continuing education programs for PAs. DISCUSSION: A paucity of published literature regarding genetics-genomics education for PAs was found. The few studies retrieved describe content being taught in PA programs, the number of genetics-genomics contact hours that PA students receive, and recommendations for continuing education programs. Most of the available literature is outdated, leaving a need for more current information to inform the education of genetic- and genomic-competent PAs. Recommendations for future research include assessment of PA programs regarding genetics-genomics education; development and validation of an assessment tool to measure genetics-genomics knowledge; and utilization of the RISE2 Genomics standards to plan, implement, evaluate, and report educational interventions. These recommendations are necessary to build an evidence base regarding genomics education for PA students and practicing PAs.

Stratification of a Phelan-McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor.

Phelan-McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials.

Digital Droplet PCR to Track SARS-CoV-2 Outbreak in a Hospital Transitional Care Unit.

We describe an outbreak of SARS-CoV-2 on a transition unit composed of elderly patients awaiting placement. Environmental and patient sample analyses using digital droplet PCR (ddPCR) suggested possible fomite transmission and a high viral burden source from a few individual patients. This outbreak illustrates challenges inherent to this specific patient population.

Linguistic Validation of Genomic Nursing Concept Inventory to Finnish Applying Mandysova's Decision Tree Algorithm.

Background and Purpose: Currently, there is no available Finnish version of the Genomic Nursing Concept Inventory tool (GNCI). This study tested the validity, reliability, and clinical usability of a Finnish translation. Methods: A decision tree algorithm was used to guide the translation, as per International Society for Pharmacoeconomics and Outcomes Research guidelines. Item-Content Validity Index (I-CVI), modified kappa (k*) statistics, and Cronbach's alpha were calculated. Results: The I-CVI and k* values were "good" to "excellent" (I-CVI = 0.63-1.00, k* = 0.52-1.00), and Cronbach's alpha value was "good" (α = 0.816; 95% confidence interval: 0.567-0.956). Conclusion: The Mandysova's decision tree algorithm provided clear and rigorous direction for the translation and validity of the Finnish GNCI.

Incidental Findings in Study Participants: What Is the Researcher's Obligation?

BACKGROUND: As technology advances and genomic testing becomes commonplace, incidental findings, or the discovery of unrelated results, have increased. The American College of Genetics and Genomics (ACMG) established recommendations for the return of pathologic variants in 78 genes in the clinical setting based on medically actionable conditions from genes linked with preventable or treatable diseases. However, the lack of policy in the research setting poses a serious ethical dilemma for researchers, potentially threatening the participant's trust and willingness to contribute to a process with more significant risk than benefit. PURPOSE: Our goal was to determine the preferred ethical approach to handling incidental research findings and suggest a new standard for investigators and participants. METHODS: By employing Wueste's IAJD Framework of ethical evaluation, the current research policy, as well as a proposed policy, were analyzed, and then a policy analysis was employed to ascertain feasibility. RESULTS AND DISCUSSION: The current policy of leaving the decision of returning incidental findings up to the researcher's discretion is an ethical failure from the consequential, deontological, and intellectual freedom perspectives. However, the proposed policy of implementing the ACMG guidance for researchers to satisfy ethical demands reinforces its moral fortitude. In a period of increasing public awareness, the community, which is the prospective research pool, has increased demands for autonomy and less paternalistic behavior from medicine and science. This paper synthesizes recommendations by numerous organizations to establish a mutually beneficial policy that will ensure the U.S. Department of Health and Human Services (HHS) goal, stated in the 2014 Joint Rule, of making participants "partners" in research a reality.