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.

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.

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.

Randomized controlled trial on the effectiveness of web-based Genomics Nursing Education Intervention for undergraduate nursing students: a study protocol.

AIM: To describe a randomized controlled trial protocol that will evaluate the effectiveness of two web-based genomic nursing education interventions. BACKGROUND: Preparing future nurses to be competent in genetic and genomic concepts is fundamental to ensure appropriate clinical application. However, genetics-genomics concepts are still new in the field of nursing. Little is known about what type and kind of web-based nursing education is effective in improving the knowledge of nursing students. To address these knowledge gaps, a web-based 'Genomic Nursing Education Intervention' will be developed and compared with an existing online education programme. DESIGN: A randomized controlled trial of two groups with pre-test and repeated posttesting. METHODS: The Genomic Nursing Concept Inventory, a validated tool, will be used to assess the genetics-genomics knowledge of nursing students. Participants will be randomly allocated to either a control or an intervention group. The control group will receive the standard web-based nursing education, while the intervention group will receive a newly developed web-based education intervention. Outcome measures include the students' knowledge level of nursing genetics-genomics concepts. Participants will be retested at 3 and 6 months. CONCLUSION: Current evidence shows that ensuring nurses have adequate education in genetic-genomic concepts is challenging. This study will demonstrate which of two web-based nursing education methods is more effective in teaching genetic-genomic concepts. This research project will better prepare the nursing profession in their careers for the emerging advance technologies in genetics-genomics and personalized health care. IMPACT: Current evidence shows major challenges in ensuring that nurses have adequate education in genetics-genomics concepts. Less is known about what approaches to web-based education are effective to improve the knowledge gaps of nursing students in genetics-genomics concepts. This study will determine which type of web-based nursing education is effective in improving the genetics-genomics knowledge of nursing students. This research project will help better prepare nurses in dealing with advances in genetics-genomics in their careers. TRIAL REGISTRATION:  This study is registered in ClinicalTrials.gov (ID number NCT03963687) https://clinicaltrials.gov/show/NCT03963687.

Isolation of Legionella pneumophila by Co-culture with Local Ameba, Canada.

Legionellosis was diagnosed in an immunocompromised 3-year-old girl in Canada. We traced the source of the bacterium through co-culture with an ameba collected from a hot tub in her home. We identified Legionella pneumophila serogroup 6, sequence type 185, and used whole-genome sequencing to confirm the environmental and clinical isolates were of common origin.

Enteric microbiome profiles during a randomized Phase 2 clinical trial of surotomycin versus vancomycin for the treatment of Clostridium difficile infection.

OBJECTIVES: The effects of surotomycin (CB-183,315, MK-4261), a bactericidal cyclic lipopeptide, and vancomycin, the current standard-of-care for Clostridium difficile infection (CDI), on intestinal pathogens and microbiota were evaluated parallel to a Phase 2 randomized, double-blind clinical trial. METHODS: The single-centre cohort included 26 patients receiving surotomycin [125 or 250 mg twice daily (n = 9 each)] or oral vancomycin [125 mg four times daily (n = 8)] for 10 days. Faecal samples were collected at days 0-42 to quantify both C. difficile by conventional culture and the major components of the microbiome by quantitative PCR. RESULTS: Surotomycin 250 mg twice daily or vancomycin 125 mg four times daily reduced faecal C. difficile counts from ∼105-107 log10 cfu/g at baseline to ≤ 102 cfu/g by days 4-10 of treatment. Day 10 counts of C. difficile in 3/9 patients receiving surotomycin 125 mg twice daily remained detectable, including one patient who failed to achieve clinical cure. Bacteroidetes and Prevotella mean counts increased 0.7 log10 or remained unchanged with surotomycin 125 and 250 mg twice daily, respectively, whereas vancomycin reduced counts by 2.5-3.2 log10 (P < 0.02). Vancomycin reduced Firmicutes counts by 2.5-2.8 log10; surotomycin moderately suppressed these microbes in a dose-dependent manner. CONCLUSIONS: In this Phase 2 trial substudy, compared with vancomycin 125 mg four times daily, surotomycin 250 mg twice daily is as active in vivo against C. difficile, but was more sparing of microbiota. Surotomycin is no longer in development due to failed Phase 3 efficacy results.

Melioidosis Causing Critical Illness: A Review of 24 Years of Experience From the Royal Darwin Hospital ICU.

OBJECTIVES: Melioidosis is increasing in incidence with newly recognized foci of melioidosis in the Americas, Africa, and elsewhere. This review describes the demographics, management, and outcomes of a large cohort of critically ill patients with melioidosis. DESIGN: Data were extracted from two prospective databases-the Menzies School of Health Research Melioidosis Database (1989-2013) and the Royal Darwin Hospital ICU Melioidosis Database (2001-2013). SETTING AND PATIENTS: The Royal Darwin Hospital ICU is the only ICU in the tropical Top End of Northern Territory of Australia, an endemic area for melioidosis. The study included all patients with melioidosis admitted to Royal Darwin Hospital ICU from 1989 to 2013. MEASUREMENTS AND MAIN RESULTS: From 1989 to 2013, 207 patients with melioidosis required admission to ICU. Mortality reduced from 92% (1989-1997) to 26% (1998-2013) (p < 0.001). The reduced mortality coincided with the introduction of an intensivist-led service, meropenem, and adjuvant granulocyte colony-stimulating factor for confirmed melioidosis sepsis in 1998. Pneumonia was the presenting illness in 155 of 207 (75%). ICU melioidosis patients (2001-2013) had an Acute Physiology and Chronic Health Evaluation II score of 23, median length of stay in the ICU of 7 days, and median ventilation hours of 130 and one third required renal replacement therapy. CONCLUSIONS: The mortality for critically ill patients with melioidosis in the Top End of the Northern Territory of Australia has substantially reduced over the past 24 years. The reduction in mortality coincided with the introduction of an intensivist-led model of care, the empiric use of meropenem, and adjunctive treatment with granulocyte colony-stimulating factor in 1998.

Faculty Performance on the Genomic Nursing Concept Inventory.

PURPOSE: To use the newly developed Genomic Nursing Concept Inventory (GNCI) to evaluate faculty understanding of foundational genomic concepts, explore relative areas of strength and weakness, and compare the results with those of a student sample. DESIGN: An anonymous online survey instrument consisting of demographic or background items and the 31 multiple-choice questions that make up the GNCI was completed by 495 nursing faculty from across the United States in the fall of 2014. METHODS: Total GNCI score and scores on four subcategories (genome basics, mutations, inheritance, genomic health) were calculated. Relationships between demographic or background variables and total GNCI score were explored. FINDINGS: The mean score on the GNCI was 14.93 (SD = 5.31), or 48% correct; topical category scores were highest on the inheritance and genomic health items (59% and 58% correct, respectively), moderate on the mutations items (54% correct), and lowest on the genome basics items (33% correct). These results are strikingly similar to those of a recent study of nursing students. Factors associated with a higher total score on the GNCI included higher self-rated proficiency with genetic/genomic content, having a doctoral degree, having taken a genetics course for academic credit or continuing education, and having taught either a stand-alone genetic/genomic course or lecture content as part of nursing or related course. Self-rated proficiency with genetic/genomic content was fair or poor (70%), with only 7% rating their proficiency as very good or excellent. CONCLUSIONS: Faculty knowledge of foundational genomic concepts is similar to that of the students they teach and weakest in the areas related to basic science information. CLINICAL RELEVANCE: Genomics is increasingly relevant in all areas of clinical nursing practice, and the faculty charged with educating the next generation of nurses must understand foundational concepts. Faculty need to be proactive in seeking out relevant educational programs that include basic genetic/genomic concepts.

The Parent Experience of Caring for a Child with Mitochondrial Disease.

UNLABELLED: Mitochondrial disease is a spectrum of progressive genetic disorders resulting from dysfunctions of cellular metabolism in the mitochondria that greatly compromise the lives of affected individuals, who are often children. PURPOSE: This study described the parent experiences unique to caring for a child with mitochondrial disease. METHODS: Internet surveys were made available to parents of children with a known mitochondrial disease. Surveys included demographic items and two questionnaires: Parent Experience of Child Illness (PECI) and Pediatric Inventory for Parents (PIP). Descriptive data were collected and correlations calculated to determine relationships between the parent experience and stress. RESULTS: The majority of participants (n=231) were mothers (95%) of children with mitochondrial disease around the age of 10 years (M=9.85). Elevated scores were found in parent adjustment illness-related concerns regarding Guilt and Worry (M=2.30, SD=.650), Sorrow and Anger (M=2.09, SD=.730), Long-term Uncertainty (M=2.56, SD=.690), and Emotional Resources (M=2.36, SD=.615). Scores indicated elevated feelings of stress in terms of both difficulty and frequency. Significant correlations (p<0.01) were found between parent illness-related concerns and parenting stress. CONCLUSIONS: The results of this study suggest that parents of a child with mitochondrial disease feel a burden of responsibility that exceeds the typical caregiver role, see their child as fragile, and have concerns about their child's future. Identification of these concerns can assist nurses to better meet the needs of these parents and families.

Stress and coping of parents caring for a child with mitochondrial disease.

UNLABELLED: Mitochondrial disease comprises a group of rare, genetic, life-limiting, neurodegenerative disorders known to affect children. Little is known about disease-related challenges, parental stress, and coping when caring for a child with a mitochondrial disease. PURPOSE: This study explored disease-related characteristics and parental stressors and coping behaviors related to caring for a child with mitochondrial disease. METHODS: Internet surveys were posted on known mitochondrial disease websites for parent completion. Surveys included demographic items and two questionnaires: Coping Inventory for Parents (CHIP) and Pediatric Inventory for Parents (PIP). Descriptive data were collected and correlations used to determine relationships between parenting stress, coping, and demographic variables. RESULTS: The majority of participants (n=231) were mothers (95%) of children with mitochondrial disease around the age of 10 years (M=9.85). On average, children had 6 organs involved (M=6.02) and saw 7 different specialists (M=7.49); 61% were hospitalized in the past year. Significant correlations (p<0.05) were found between parenting stress and parent age, parent income, parent education, child age, child age at diagnosis, presence of developmental delays, number of hospitalizations, number of medical visits, number of organs involved, and number of specialists seen. Significant correlations were also found between parenting stress and coping behaviors such as family integration, social support and understanding health care. CONCLUSIONS: The ability to identify disease-related challenges, stressors, and coping strategies in parents of children with mitochondrial disease is novel and can assist nurses to provide disease-sensitive, family-focused care and improve child health outcomes.

Differences of the Fecal Microflora With Clostridium difficile Therapies.

BACKGROUND: During treatment of Clostridium difficile infection (CDI), patterns of pathogen reduction in relationship to changes in components of the normal microbiota are hypothesized to be predictive of response to treatment and subsequent sustained cure. METHODS: At a single center, subjects enrolled into phase 2 and 3 C. difficile treatment clinical trials (2003-2008) provided fecal samples to assess killing of C. difficile and changes to components of the microbiome. Quantitative bacterial cultures, measurement of C. difficile toxin titers, quantitative polymerase chain reaction of fecal samples for Bacteroidetes, Clostridium clusters XIVa and IV, and C. difficile were performed. RESULTS: Quantitative bacterial cultures showed a mean log10 C. difficile count (colony-forming units [CFU]) of 6.7 ± 2.0 at study entry; vancomycin treatment consistently reduced C. difficile counts to the limit of detection (2.0 log10 CFU/g), whereas metronidazole was associated with mean C. difficile counts 1.5-2 log10 higher at 10 days of treatment. In patients receiving tolevamer, C. difficile persisted in high counts during treatment; response to treatment was correlated with neutralization of toxin along with persistence of normal microbiota components. However, this was achieved in approximately half of subjects. Both vancomycin and metronidazole further suppressed microbiome components during treatment of CDI. Lactobacilli were observed to be a microbiome component that persisted during treatment of CDI. CONCLUSIONS: Differences of pathogen clearance and microbiome perturbation during treatment of CDI appear to explain treatment outcomes. The hypothesis that probiotic microbes could help prevent onset of CDI is supported by the observation of persistence of lactobacilli during and after treatment of CDI.

Clinical presentation and medical management of melioidosis in children: a 24-year prospective study in the Northern Territory of Australia and review of the literature.

BACKGROUND: Melioidosis is less common in children than adults. The clinical spectrum of disease varies greatly between the 2 groups. Treatment guidelines are currently based on adult studies, and revision of existing guidelines is necessary to instruct specific pediatric management. METHODS: Culture-confirmed cases of melioidosis in the Northern Territory between 1989 and 2013 were identified from the Prospective Melioidosis Study. The epidemiology and clinical spectrum of disease for children aged ≤ 16 years were analyzed and compared with the adult data. RESULTS: Forty-five pediatric patients were identified, representing 5% of the total 820 melioidosis cases over 24 years. Most children (84%) had no recognized risk factors for melioidosis, and 80% presented during the wet season. Primary cutaneous melioidosis was the commonest presentation in children (60% vs 13%; P < .001), whereas pneumonia predominated in adults (54% vs 20%; P < .001). Bacteremia was less common in children than in adults (16% vs 59%; P < .001). Brainstem encephalitis occurred in 3 children without risk factors. Children were more likely to report an inoculating event (42%; P < .001). There was no difference in mortality between the groups (P = .178), with 3 children dying (7%); all had identifiable risk factors. Four children with cutaneous melioidosis were successfully treated with oral therapy alone, while 2 had skin lesions that resolved spontaneously. CONCLUSIONS: Pediatric melioidosis commonly manifests as localized cutaneous disease in immunocompetent hosts. The disease can be fatal, especially in individuals with risk factors for disease. Melioidosis with encephalomyelitis can result in severe residual disability. Prompt diagnosis requires a high index of clinical suspicion in endemic areas.

Recurrent melioidosis in the Darwin Prospective Melioidosis Study: improving therapies mean that relapse cases are now rare.

The Darwin Prospective Melioidosis Study has documented 785 melioidosis cases over 23 years. Recurrent melioidosis occurred in 39/679 (5.7%) patients surviving initial infection; 29 patients suffered relapse of the original infection, and 10 presented with a new Burkholderia pseudomallei infection. With improved therapy, relapse has become rare in recent years.

Decreasing prevalence of Trichuris trichiura (whipworm) in the Northern Territory from 2002 to 2012.

OBJECTIVE: To observe the prevalence, disease associations, and temporal trends in Trichuris trichiura (whipworm) infection in the Northern Territory between 2002 and 2012. DESIGN, PARTICIPANTS AND SETTING: Retrospective observational analysis of consecutive microbiologically confirmed cases of T. trichiura infection among members of the NT population from whom a faecal sample was obtained for testing by NT Government health care facilities between 1 January 2002 and 31 December 2012. MAIN OUTCOME MEASURES: Annual prevalence of T. trichiura infection; age, sex, Indigenous status and place of residence of infected patients; percentage of infected patients with anaemia (haemoglobin level, ≤ 110 g/L) and eosinophilia (eosinophil count, ≥ 0.5 × 10(9)/L). RESULTS: 417 episodes of T. trichiura infection were identified over the 11 years from 63 668 faecal samples. The median age of patients was 8 years (interquartile range [IQR], 3-36 years). Patients were predominantly Indigenous (95.3%; P = 0.001) and from three main geographical areas (Victoria Daly, East Arnhem Land and West Arnhem Land). Infections were associated with anaemia (40.2%) and eosinophilia (51.6%). There was a downward trend in the prevalence of T. trichiura infection diagnosed at NT Government health care facilities, from 123.1 cases (95% CI, 94.8-151.3 cases) per 100,000 Indigenous population in 2002 to 35.8 cases (95% CI, 21.8-49.9 cases) per 100,000 Indigenous population in 2011. CONCLUSIONS: T. trichiura is the most frequently identified soil-transmitted helminth infecting patients in NT Government health care facilities. Cases are identified predominantly in Indigenous patients in remote communities. We have observed a declining prevalence of whipworm infection in the NT.

The role of AAA+ proteases in mitochondrial protein biogenesis, homeostasis and activity control.

Mitochondria are specialised organelles that are structurally and functionally integrated into cells in the vast majority of eukaryotes. They are the site of numerous enzymatic reactions, some of which are essential for life. The double lipid membrane of the mitochondrion, that spatially defines the organelle and is necessary for some functions, also creates a physical but semi-permeable barrier to the rest of the cell. Thus to ensure the biogenesis, regulation and maintenance of a functional population of proteins, an autonomous protein handling network within mitochondria is required. This includes resident mitochondrial protein translocation machinery, processing peptidases, molecular chaperones and proteases. This review highlights the contribution of proteases of the AAA+ superfamily to protein quality and activity control within the mitochondrion. Here they are responsible for the degradation of unfolded, unassembled and oxidatively damaged proteins as well as the activity control of some enzymes. Since most knowledge about these proteases has been gained from studies in the eukaryotic microorganism Saccharomyces cerevisiae, much of the discussion here centres on their role in this organism. However, reference is made to mitochondrial AAA+ proteases in other organisms, particularly in cases where they play a unique role such as the mitochondrial unfolded protein response. As these proteases influence mitochondrial function in both health and disease in humans, an understanding of their regulation and diverse activities is necessary.

"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.

Dominance of Haemophilus influenzae in ear discharge from Indigenous Australian children with acute otitis media with tympanic membrane perforation.

BACKGROUND: Indigenous Australian children living in remote communities experience high rates of acute otitis media with tympanic membrane perforation (AOMwiP). Otitis media in this population is associated with dense nasopharyngeal colonization of three primary otopathogens; Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Little is known about the relative abundance of these pathogens during infection. The objective of this study was to estimate the abundance and concordance of otopathogens in ear discharge and paired nasopharyngeal swabs from children with AOMwiP (discharge of not more than 6 weeks' duration and perforation size <2%). METHODS: Culture and quantitative PCR (qPCR) estimation of H. influenzae, S. pneumoniae, M. catarrhalis and total bacterial load were performed on paired nasopharyngeal and ear discharge swabs from 55 Indigenous children with AOMwiP aged 3.5 - 45.6 months and resident in remote communities. RESULTS: By culture, H. influenzae, S. pneumoniae, and M. catarrhalis were detected in 80%, 84% and 91% of nasopharyngeal swabs, and 49%, 33% and 4% of ear discharge swabs, respectively. Using qPCR, H. influenzae, S. pneumoniae, and M. catarrhalis were detected in 82%, 82%, and 93% of nasopharyngeal swabs, and 89%, 41% and 18% of ear discharge swabs, respectively. Relative abundance of H. influenzae in ear discharge swabs was 0-68% of the total bacterial load (median 2.8%); whereas S. pneumoniae and M. catarrhalis relative abundances were consistently <2% of the total bacterial load. S. pneumoniae and M. catarrhalis abundances were significantly lower in ear discharge compared with nasopharyngeal swabs (p = 0.001, p < 0.001); no significant difference was observed in H. influenzae mean abundance at the two sites. CONCLUSIONS: H. influenzae was the dominant otopathogen detected in ear discharge swabs collected from children with AOMwiP. High prevalence and abundance of S. pneumoniae and M. catarrhalis in the nasopharynx did not predict ear discharge prevalence and abundances of these pathogens. PCR was substantially more sensitive than culture for ear discharge, and a necessary adjunct to standard microbiology. Quantitative methods are required to understand species abundance in polymicrobial infections and may be needed to measure accurately the microbiological impact of interventions and to provide a better understanding of clinical failure in these children.

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.

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.