"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.

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.

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.

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.

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.

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.

Sleep and Phelan-McDermid Syndrome: Lessons from the International Registry and the scientific literature.

BACKGROUND: Sleep is essential to maintaining a healthy life. Sleep disturbances among individuals with neurodevelopmental disorders are not well studied, affecting their early detection and treatment. Sleep disturbances in individuals with Phelan-McDermid Syndrome (PMS) are among the primary concerns reported by parents. However, little research has been aimed at addressing their concern. METHODS: The purpose of this investigation was to identify and quantify specific sleep disturbances in people with PMS by analyzing data collected by the PMS Foundation International Registry. RESULTS: The registry shows that 284 out of 384 (73.4%) individuals with confirmed chromosome 22q13 deletions or SHANK3 pathogenic variants have a sleep disturbance. The prevalence of sleep disturbances increases with age with 56% reporting a sleep disturbance in the 0-3 year age group and 90% reporting these disturbances in those over age 18 years old. The primary sleep disturbances were circadian rhythm sleep disorders that included difficulty falling asleep, frequent nighttime awakenings, difficulty returning to sleep after a nighttime awakening event, and hypersomnia and parasomnias including enuresis, night terrors, sleepwalking, and sleep apnea. Sleep disturbances were similarly frequent among individuals with SHANK3 pathogenic variants (84.8%) and those with deletions (71.9%), supporting the role of haploinsufficiency of SHANK3 in sleep. CONCLUSION: Sleep disturbances are a common feature of PMS and should be considered in clinical evaluation and management because of the effect they have on the quality of life of the patients and their families.

Melioidosis in the remote Katherine region of northern Australia.

Melioidosis is endemic in the remote Katherine region of northern Australia. In a population with high rates of chronic disease, social inequities, and extreme remoteness, the impact of melioidosis is exacerbated by severe weather events and disproportionately affects First Nations Australians. All culture-confirmed melioidosis cases in the Katherine region of the Australian Top End between 1989-2021 were included in the study, and the clinical features and epidemiology were described. The diversity of Burkholderia pseudomallei strains in the region was investigated using genomic sequencing. From 1989-2021 there were 128 patients with melioidosis in the Katherine region. 96/128 (75%) patients were First Nations Australians, 72/128 (56%) were from a very remote region, 68/128 (53%) had diabetes, 57/128 (44%) had a history of hazardous alcohol consumption, and 11/128 (9%) died from melioidosis. There were 9 melioidosis cases attributable to the flooding of the Katherine River in January 1998; 7/9 flood-associated cases had cutaneous melioidosis, five of whom recalled an inoculating event injury sustained wading through flood waters or cleaning up after the flood. The 126 first-episode clinical B. pseudomallei isolates that underwent genomic sequencing belonged to 107 different sequence types and were highly diverse, reflecting the vast geographic area of the study region. In conclusion, melioidosis in the Katherine region disproportionately affects First Nations Australians with risk factors and is exacerbated by severe weather events. Diabetes management, public health intervention for hazardous alcohol consumption, provision of housing to address homelessness, and patient education on melioidosis prevention in First Nations languages should be prioritised.

Detection and quantification of infectious severe acute respiratory coronavirus-2 in diverse clinical and environmental samples.

To explore the potential modes of Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) transmission, we collected 535 diverse clinical and environmental samples from 75 infected hospitalized and community patients. Infectious SARS-CoV-2 with quantitative burdens varying from 5 plaque-forming units/mL (PFU/mL) up to 1.0 × 106 PFU/mL was detected in 151/459 (33%) of the specimens assayed and up to 1.3 × 106 PFU/mL on fomites with confirmation by plaque morphology, PCR, immunohistochemistry, and/or sequencing. Infectious virus in clinical and associated environmental samples correlated with time since symptom onset with no detection after 7-8 days in immunocompetent hosts and with N-gene based Ct values ≤ 25 significantly predictive of yielding plaques in culture. SARS-CoV-2 isolated from patient respiratory tract samples caused illness in a hamster model with a minimum infectious dose of ≤ 14 PFU. Together, our findings offer compelling evidence that large respiratory droplet and contact (direct and indirect i.e., fomites) are important modes of SARS-CoV-2 transmission.

The Darwin Prospective Melioidosis Study: a 30-year prospective, observational investigation.

BACKGROUND: The global distribution of melioidosis is under considerable scrutiny, with both unmasking of endemic disease in African and Pacific nations and evidence of more recent dispersal in the Americas. Because of the high incidence of disease in tropical northern Australia, The Darwin Prospective Melioidosis Study commenced in October, 1989. We present epidemiology, clinical features, outcomes, and bacterial genomics from this 30-year study, highlighting changes in the past decade. METHODS: The present study was a prospective analysis of epidemiological, clinical, and laboratory data for all culture-confirmed melioidosis cases from the tropical Northern Territory of Australia from Oct 1, 1989, until Sept 30, 2019. Cases were identified on the basis of culture-confirmed melioidosis, a laboratory-notifiable disease in the Northern Territory of Australia. Patients who were culture-positive were included in the study. Multivariable analysis determined predictors of clinical presentations and outcome. Incidence, survival, and cluster analyses were facilitated by population and rainfall data and genotyping of Burkholderia pseudomallei, including multilocus sequence typing and whole-genome sequencing. FINDINGS: There were 1148 individuals with culture-confirmed melioidosis, of whom 133 (12%) died. Median age was 50 years (IQR 38-60), 48 (4%) study participants were children younger than 15 years of age, 721 (63%) were male individuals, and 600 (52%) Indigenous Australians. All but 186 (16%) had clinical risk factors, 513 (45%) had diabetes, and 455 (40%) hazardous alcohol use. Only three (2%) of 133 fatalities had no identified risk. Pneumonia was the most common presentation occurring in 595 (52%) patients. Bacteraemia occurred in 633 (56%) of 1135 patients, septic shock in 240 (21%) patients, and 180 (16%) patients required mechanical ventilation. Cases correlated with rainfall, with 80% of infections occurring during the wet season (November to April). Median annual incidence was 20·5 cases per 100 000 people; the highest annual incidence in Indigenous Australians was 103·6 per 100 000 in 2011-12. Over the 30 years, annual incidences increased, as did the proportion of patients with diabetes, although mortality decreased to 17 (6%) of 278 patients over the past 5 years. Genotyping of B pseudomallei confirmed case clusters linked to environmental sources and defined evolving and new sequence types. INTERPRETATION: Melioidosis is an opportunistic infection with a diverse spectrum of clinical presentations and severity. With early diagnosis, specific antimicrobial therapy, and state-of-the-art intensive care, mortality can be reduced to less than 10%. However, mortality remains much higher in the many endemic regions where health resources remain scarce. Genotyping of B pseudomallei informs evolving local and global epidemiology. FUNDING: The Australian National Health and Medical Research Council.

Nursing Education Amid a Pandemic: Mental Health in a Time of Virtual Learning.

BACKGROUND: The unprecedented pandemic presented new stresses and challenges in nursing education impacting the mental health of nursing students. PURPOSE: The purpose of this study was to evaluate the relationship between virtual learning and the mental health of nursing students. METHOD: This study used a descriptive, cross-sectional design with a convenience sample of 256 nursing students enrolled in a baccalaureate program. Data were collected through an online survey using 2 screening tools for stress, anxiety, and depression. RESULTS: Mean sum Patient Health Questionnaire-4 scores and subscale scores suggest that more than 40% of students experienced mild to moderate levels of psychological distress. Mean sum Perceived Stress Scale-10 scores indicate 84% of students experienced moderate levels of stress, and 14% experienced high levels of stress. CONCLUSIONS: During periods of societal crisis, faculty must be hypervigilant to the mental health needs of students.

Emergence of Burkholderia pseudomallei Sequence Type 562, Northern Australia.

Since 2005, the range of Burkholderia pseudomallei sequence type 562 (ST562) has expanded in northern Australia. During 2005-2019, ST562 caused melioidosis in 61 humans and 3 animals. Cases initially occurred in suburbs surrounding a creek before spreading across urban Darwin, Australia and a nearby island community. In urban Darwin, ST562 caused 12% (53/440) of melioidosis cases, a proportion that increased during the study period. We analyzed 2 clusters of cases with epidemiologic links and used genomic analysis to identify previously unassociated cases. We found that ST562 isolates from Hainan Province, China, and Pingtung County, Taiwan, were distantly related to ST562 strains from Australia. Temporal genomic analysis suggested a single ST562 introduction into the Darwin region in ≈1988. The origin and transmission mode of ST562 into Australia remain uncertain.

Strongyloides stercoralis seropositivity is not associated with increased symptoms in a remote Aboriginal community.

BACKGROUND: Strongyloides stercoralis is a soil-transmitted helminth, endemic in remote Aboriginal and Torres Strait Islander communities in northern Australia with estimates of prevalences up to 60%. Hyperinfection in the setting of immunosuppression is a rare, but well recognised cause of significant morbidity and mortality. However, the morbidity associated with chronic uncomplicated infection is less well characterised. AIMS: To measure the prevalence of symptoms potentially attributable to S. stercoralis infection and their association with seropositivity. METHODS: This retrospective matched case-control study reviewed records of primary healthcare presentations for symptoms in the 12 months before and after an ivermectin mass drug administration (MDA) in a remote Aboriginal community. RESULTS: One hundred and seventy-five S. stercoralis seropositive cases were matched with 175 seronegative controls. The most frequently reported symptom overall in the 12 months prior to the MDA was cough followed by abdominal pain, weight loss/malnutrition, diarrhoea and pruritis. Seropositive cases were not more likely than matched controls to have symptoms typically attributed to strongyloidiasis. In the seropositive cohort, we found no difference in symptoms in the 12 months before and after an ivermectin MDA despite a reduction in seroprevalence. CONCLUSION: We found no evidence to suggest that S. stercoralis seropositivity was associated with increased symptoms when compared to matched seronegative controls. Treatment with ivermectin did not reduce symptoms in seropositive cases. Without evidence to support that population-based screening or treatment programmes reduce symptoms, the emphasis must remain on identifying and managing those few individuals with immunosuppression that predisposes them to potentially life-threatening hyperinfection.

2020 Review and revision of the 2015 Darwin melioidosis treatment guideline; paradigm drift not shift.

BACKGROUND: Melioidosis therapy is divided into an intravenous intensive phase and an oral eradication phase. The Darwin melioidosis treatment guideline has evolved over two decades, with over 1150 consecutive patients with culture-confirmed melioidosis managed under the Darwin Prospective Melioidosis Study. The current guideline, published in 2015, has been associated with low rates of recrudescence, relapse and mortality, and together with the treatment trials in Thailand, forms the basis for consensus global guidelines. We aimed to reassess the Darwin guideline and determine if any adjustments to the recommendations better reflect current practice in melioidosis therapy at Royal Darwin Hospital. METHODOLOGY/PRINCIPAL FINDINGS: This retrospective cohort study reviews the characteristics, admission duration, duration of intravenous antibiotics, recrudescence, recurrence and mortality in all patients presenting with first episode culture-confirmed melioidosis in the tropical north of Australia's Northern Territory from 1st October 2012 until 1st January 2017. 234 patients were available for analysis. 16 (6.8%) died during the intensive phase treatment and 6 (2.6%) did not have complete treatment at Royal Darwin Hospital, leaving 212 patients for analysis. Six (2.8%) patients had recrudescence during therapy and 10 (4.7%) had recurrent melioidosis (relapse or new infection) after completion of therapy. Persisting osteomyelitis requiring surgery was an important reason for recrudescence as was unrecognized osteomyelitis for relapse. For patients presenting with an antibiotic duration determining focus of pneumonia, durations of intravenous antibiotics were often prolonged beyond the current 2-week minimum treatment recommendation. Prolongation of therapy in pneumonia mostly occurred in patients presenting with multi-lobar disease or with concurrent blood culture positivity. CONCLUSIONS/SIGNIFICANCE: The 2015 Darwin melioidosis guideline is working well with low rates of recrudescence, relapse and mortality. Based on the practice of the treating clinicians, the 2020 revision of the guideline has been adjusted to include a duration of a minimum of 3 weeks of intravenous antibiotics for those with concurrent bacteraemia and pneumonia involving only a single lobe and those with bilateral and unilateral multi-lobar pneumonias who do not have bacteraemia. We also extend to a minimum of 4 weeks intravenous therapy for those with concurrent bacteraemia and bilateral or unilateral multi-lobar pneumonia.