Exploring stakeholders' perspectives on antibiogram use, development, and implementation in residential aged care settings.

BACKGROUND: Knowledge of local antibiotic resistance data provided by antibiograms (cumulative-antimicrobial-susceptibility-tests) can assist prescribers to make appropriate empirical antibiotic choices. OBJECTIVE: This study explored the perceptions and knowledge of key stakeholders about the role of antibiograms in residential aged care facilities (RACF), and to understand barriers and enablers of antibiogram development and implementation in this setting. METHOD: Semi-structured interviews were conducted with aged-care health professionals ('end-users') and antibiogram content experts. This study was conducted in Queensland, Australia in 2023. Using qualitative techniques, framework thematic analysis was used to identify themes, which were mapped to the 'Integrated Promoting Action on Research Implementation in Health Services' framework constructs. RESULTS: Twenty interviews were conducted comprising of five 'content-experts' and fifteen 'end-users'. Five themes were identified which indicated lack of knowledge about how to use antibiograms, and its availability. Potential insufficient data was the primary issue identified by content experts with regards to feasibility of annual antibiograms. Pragmatic solutions were offered, such as pooling pathology data from facilities in the same geographical location, extending antibiogram data to two-or three-yearly, or utilising local hospital antibiograms. Presenting antibiogram data in a mode and format suiting preferences of individual users would encourage uptake and improve usability. Antimicrobial stewardship (AMS) champions and pharmacists were highlighted as drivers of educating and promoting antibiogram use. CONCLUSION: Clinicians recognised the potential role of antibiograms in improving empirical antibiotic prescribing choices. Establishing their baseline knowledge provides an essential starting point for the education needs of this group. This study provides practical recommendations regarding the presentation of antibiograms to ensure appropriate use and uptake as an AMS tool in RACFs. Pragmatic solutions suggested to overcome challenges of antibiogram development for RACFs should be applied and evaluated to determine feasibility of RACF-specific antibiograms.

Understanding Australian pharmacy degree holders' job preferences through the lens of motivation-hygiene theory.

Increasing the contribution of pharmacists to primary care has been long discussed, particularly in the context of health workforce shortages and the push to better integrate all providers across primary care. This study examines the employment preferences of Australian pharmacy degree holders (PDHs) elicited through a discrete choice experiment (DCE), to better understand the drivers of current labour force choices. A labelled DCE was developed incorporating the six employment sectors: hospital pharmacy, community pharmacy, primary healthcare settings, pharmaceutical industry, government/academia, and non-pharmacy-related sector. Each alternative was described by five attributes using Herzberg's Two Factor Theory as a conceptual framework. They include motivators - role and career opportunities, and hygiene factors-flexible work schedule, geographic location, and salary. Unforced choice data were analysed using conditional logit and mixed logit models. Based on a sample of 678 PDHs in Australia, our findings indicated pharmaceutical industry is the least preferred sector, followed by non-pharmacy-related sector. Motivators in the form of role and career opportunities are the most important attributes in hospital pharmacy while hygiene factors - geographic location and salary significantly drive the choice of community pharmacy and primary care settings. We provided evidence of a willingness to adopt expanded roles in community pharmacy. This unique interpretation of the key drivers of employment preference in light of motivators and hygiene factors provides policy makers with important information when designing policies to attract and retain PDHs across employment sectors.

Sponge-derived matter is assimilated by coral holobionts.

Coral reef biodiversity is maintained by a complex network of nutrient recycling among organisms. Sponges assimilate nutrients produced by other organisms like coral and algae, releasing them as particulate and dissolved matter, but to date, only a single trophic link between sponge-derived dissolved matter and a macroalgae has been identified. We sought to determine if sponge-coral nutrient exchange is reciprocal using a stable isotope 'pulse-chase' experiment to trace the uptake of 13C and 15N sponge-derived matter by the coral holobiont for three coral species (Acropora cervicornis, Orbicella faveolata, and Eunicea flexuosa). Coral holobionts incorporated 2.3-26.8x more 15N than 13C from sponge-derived matter and A. cervicornis incorporated more of both C and N than the other corals. Differential isotopic incorporation among coral species aligns with their ecophysiological characteristics (e.g., morphology, Symbiodiniaceae density). Our results elucidate a recycling pathway on coral reefs that has implications for improving coral aquaculture and management approaches.

Clinical impact of antibiograms as an intervention to optimize antimicrobial prescribing and patient outcomes-A systematic review.

BACKGROUND: Antimicrobial stewardship (AMS) guidelines advocate for the use of antibiograms (cumulative antimicrobial susceptibility test data) as a tool to guide empirical antibiotic prescribing and inform local treatment guidelines. The objective of this review is to evaluate the effectiveness of antibiograms as an intervention to optimize antimicrobial prescribing and patient outcomes. METHODS: Embase, PubMed, CINAHL, and International Pharmacy Abstracts (IPA) databases were searched from inception until September 2022, to identify studies of antibiogram-related interventions in all health care settings. The National Institutes of Health Quality Assessment Tools were used to assess the methodological quality of the included studies. RESULTS: Of the 37 included studies, the majority of studies were conducted in the United States (n = 25) and in hospital settings (n = 27). All interventions were multifaceted and in 26 (70%) studies, facility-specific antibiograms could be considered as an integral component of the interventions. A positive impact on antibiotic consumption trends (17 studies), appropriateness of prescribing (16 studies), and cost of treatment (6 studies) was found, with minimal evidence for improvement in mortality, hospitalization, and resistance profiles. Due to the heterogeneity in study designs and outcomes, a meta-analysis was not performed. CONCLUSIONS: AMS interventions including antibiograms may improve antibiotic use, appropriateness, and costs. Multifaceted interventions were often used, which precludes drawing conclusions about the effectiveness of antibiograms alone as an AMS tool.

Clinical Utility and Reimbursement of Next-Generation Sequencing-Based Testing for Myeloid Malignancies.

Next-generation sequencing is becoming increasingly important for the diagnosis, risk stratification, and management of patients with established or suspected myeloid malignancies. These tests are being incorporated into clinical practice guidelines and many genetic alterations now constitute disease classification criteria. However, the reimbursement for these tests is uncertain. This study analyzed the clinical impact, ordering practices, prior authorization, and reimbursement outcomes of 505 samples from 477 patients sequenced with a 50-gene myeloid next-generation sequencing panel or a 15-gene myeloproliferative neoplasm subpanel. Overall, 98% (496 of 505) of tests provided clinically useful data. Eighty-nine percent of test results, including negative findings, informed or clarified potential diagnoses, 94% of results informed potential prognoses, and 19% of tests identified a potential therapeutic target. Sequencing results helped risk-stratify patients whose bone marrow biopsy specimens were inconclusive for dysplasia, monitor genetic evolution associated with disease progression, and delineate patients with mutation-defined diagnoses. Despite the clinical value, prior authorization from commercial payors or managed government payors was approved for less than half (45%) of requests. Only 51% of all cases were reimbursed, with lack of medical necessity frequently cited as a reason for denial. This study demonstrates the existence of a substantial gap between clinical utility and payor policies on test reimbursement.

Iterative learning control for piecewise arc path tracking with validation on a gantry robot manufacturing platform.

The piecewise arc path tracking problem is a common feature of manufacturing systems operating in a repetitive mode, e.g. assembly production lines. Here, the system end-effector must follow a spatial path without any specific temporal tracking constraints, which makes the temporal profile not fixed a priori. The technique of iterative learning control (ILC) is well-suited to handle this problem, since compared to classical feedback control methods, ILC is capable of learning from previous trial information to minimize the tracking error over repeated trials. This paper extends the ILC task description to address piecewise arc path tracking tasks, and further formulates a more general design framework than existing spatial ILC approaches. A comprehensive ILC algorithm is designed to handle this class of piecewise arc path tracking problems, and practical implementation instructions are provided. Validation is conducted on a gantry robot manufacturing testbed to confirm its feasibility and efficiency in practice with a comparison to existing methods showing its higher path tracking accuracy.

A collaborative pharmacist prescribing model for patients with chronic disease(s) attending Australian general practices: Patient and general practitioner perceptions.

A collaborative pharmacist prescribing model for patients with chronic disease(s) attending Australian general practices: patient and general practitioner perceptions. Background: Pharmacists working in general practice settings are slowly emerging in Australia, with comprehensive medication reviews forming a large part of their role in optimising pharmaceutical care. In Australia, pharmacists are entirely reliant on general practitioners (GPs) accepting and implementing their recommendations to manage drug related problems (DRPs). The next step is a model where the pharmacist takes on responsibility for implementing some of their recommendations. Aim: To investigate patient and general practitioner perceptions of a collaborative model of care where the pharmacist has increased responsibility in assisting the general practitioner manage patients with chronic conditions. Method: Semi-structured, phone and face-to-face interviews were conducted with a purposive sample of patients and GPs respectively. Data were transcribed by a professional transcription service, collated using NVivo 12 Plus and analysed using Braun and Clarke's thematic analysis. Provisional codes were generated and clustered into categories, from which themes were identified. Results: Eighteen interviews were conducted (12 patients, 6 GPs). Four themes were identified from the patient interview data: pharmacist attributes; acknowledgement of the impact of the pharmacist, understanding of the GP-pharmacist collaborative model; relationships with and attitudes towards medicines and health care providers. Four themes were identified from the general practitioner interview data: pharmacist attributes; relationships with pharmacists; impressions on collaboration; impressions of the pharmacist's recommendations. Patients' and GPs' perceptions of the collaborative model of care overall were positive, acknowledging the advantages of a patient-centred, interdisciplinary approach and the potential benefits to patients. Conclusion: The GP-pharmacist collaborative model was viewed favourably by patients and GPs, with some GPs articulating the value in the pharmacist's increased responsibility as they implemented some recommendations to manage DRPs.

Oral examination of fourth-year medical students on surgery rotations allows faculty to assess Core Entrustable Professional Activities for entering Residency (CEPAR): Proof-of-concept and analysis of student submissions.

BACKGROUND: As a community-based medical school which recruited faculty preceptors new to teaching, we sought to create objective assessments for fourth-year surgery experiences via administration of an oral exam. Students provided three authentic cases, which faculty used as a springboard to ascertain student proficiency in five entrustable professional activities: 1-oral presentation, 2-recognition of urgency/instability, 3-calling consults, 4-transitions of care, 5-informed consent. We present proof-of-concept and analysis of student case submissions. METHODS: Twenty-seven student submissions (79 cases in total) were evaluated for case complexity, level-appropriateness, and an estimation of the ability to conduct a quality exam based on the information provided (subjective measures). Objective metrics included word count, instruction adherence, inclusion of figures/captions. A resident-in-training rated cases via the same metrics. In-examination data was separately culled. RESULTS: The average word count was 281.70 (SD 140.23; range 40-743). Figures were included in 26.1% of cases. Faculty raters scored 29.0% as low-complexity, 37.7% medium-complexity, and 33.3% high-complexity. Raters felt 62.3% of cases provided enough information to conduct a quality exam. The majority of cases submitted (65.2%) were level-appropriate or higher. The resident rater scored cases more favorably than surgeons (Cohen's kappa of -0.5), suggesting low inter-rater agreement between those of differing experience levels. CONCLUSION: Student's case submissions lessened faculty burden and provided assessors with adequate information to deliver a quality exam to assess proficiency in clinical skills essential for residency. Cases demonstrated sufficient complexity and level-appropriateness. The request to correlate case rating with exam performance is under review by our institution's assessment office. Near-peer tutoring by resident alumni is a program under development.

Limited Metabolomic Overlap between Commensal Bacteria and Marine Sponge Holobionts Revealed by Large Scale Culturing and Mass Spectrometry-Based Metabolomics: An Undergraduate Laboratory Pedagogical Effort at Georgia Tech.

Sponges are the richest source of bioactive organic small molecules, referred to as natural products, in the marine environment. It is well established that laboratory culturing-resistant symbiotic bacteria residing within the eukaryotic sponge host matrix often synthesize the natural products that are detected in the sponge tissue extracts. However, the contributions of the culturing-amenable commensal bacteria that are also associated with the sponge host to the overall metabolome of the sponge holobiont are not well defined. In this study, we cultured a large library of bacteria from three marine sponges commonly found in the Florida Keys. Metabolomes of isolated bacterial strains and that of the sponge holobiont were compared using mass spectrometry to reveal minimal metabolomic overlap between commensal bacteria and the sponge hosts. We also find that the phylogenetic overlap between cultured commensal bacteria and that of the sponge microbiome is minimal. Despite these observations, the commensal bacteria were found to be a rich resource for novel natural product discovery. Mass spectrometry-based metabolomics provided structural insights into these cryptic natural products. Pedagogic innovation in the form of laboratory curricula development is described which provided undergraduate students with hands-on instruction in microbiology and natural product discovery using metabolomic data mining strategies.

A community pharmacy practice-based research network: A protocol for a realist evaluation.

BACKGROUND: Community pharmacists' active participation in research is essential to build a robust, translatable evidence base. Practice-based research networks (PBRNs) have been established to support collaborative research and knowledge translation in community pharmacies. However, PBRNs' effectiveness in supporting research engagement and knowledge translation remains unexplored. A new PBRN will be implemented in southeast Queensland, Australia. This realist evaluation seeks to explain whether, how, why, for whom, in what context and over what duration the PBRN supports community pharmacists to engage in research. OBJECTIVES: 1. to generate transferable knowledge about the different circumstances in which-and the mechanisms by which-a PBRN influences research engagement outcomes for different community pharmacists, in the form of a program theory. 2. To use the program theory to develop evidence-informed recommendations for use by PBRN stakeholders. METHODS: A realist evaluation will be conducted in four iterative phases: (1) theory development, (2) hypothesis generation, (3) observations, and (4) theory refinement. A two-year multi-method study will be conducted, including interviews with pharmacists, surveys, participatory and observational data collection. The evidence will be used to confirm, refute, and/or refine the program theory. The evaluation will adhere to the Realist And Meta-Narrative Evidence Synthesis (RAMESES) publication and quality standards. CONCLUSIONS: The evaluation will contribute to the body of knowledge by generating a realist program theory to explain how, why, for whom, in what contexts, to what extent, in what respects, and over what duration the PBRN supports community pharmacists to engage in research. The findings will support the broader implementation of PBRNs and future network activities.

Feasibility of a collaborative pharmacist prescribing model for patients with chronic disease(s) attending Australian general practices: a preliminary study.

BACKGROUND: Pharmacists working in general practices provide medication reviews with recommendations to general practitioners (GPs) to optimise medications. We describe a model where the pharmacist is empowered with increased responsibility to implement agreed recommendations through collaborative prescribing. AIM: To assess a collaborative pharmacist prescribing model incorporating increased pharmacist responsibility, for patients with chronic diseases in general practice. METHOD: This was a pre-test-post-test quasi experimental pilot study using a pharmacist embedded in three Australian general practices. A pharmaceutical care plan was developed with patients and their GP to identify drug related problems (DRPs). The pharmacist discussed recommendations to manage DRPs with the GP and implemented recommendations agreed by the GP and patient over the six-month study period. Outcome measures included acceptance and implementation rate of recommendations made by the pharmacist. RESULTS: The pharmacist made 135 recommendations to optimise medicine use of which 126 (93.3%) were accepted by the GP. There were 105 (83.3%) implemented by the end of the study of which the pharmacist implemented 62 (49.3%). CONCLUSION: Compared to other Australian studies using a general practice pharmacist model, this study suggested increased pharmacist responsibility through collaborative prescribing led to high acceptance and implementation rates of recommendations to manage DRPs.

Quality metrics for enhanced performance of an NGS panel using single-vial amplification technology.

AIMS: Targeted next-generation sequencing (NGS) panels, which identify genomic alterations, are the stronghold of molecular oncology laboratories. In spite of technological advances, the quantity and quality of DNA from formalin-fixed paraffin-embedded tissue and paucicellular specimens are barriers to successful sequencing. Here, we describe an NGS assay employing single tube stem-loop inhibition mediated amplification technology that delivers highly accurate results with low input DNA. Rigorous quality metrics, regular monitoring and in-depth validation make the test attractive for clinical laboratories. METHODS: The study used a customised NGS panel, targeting 48 genes across several solid tumour types. Validation, in accordance with guidelines from New York State, sequenced patient samples harbouring 136 known variants, including single-nucleotide variants (SNVs) and indels. Specimen types included formalin-fixed paraffin embedded blocks, core biopsies and cytology material. Neoplastic cellularity of the tumours ranged from 10% to 80%. RESULTS: The assay was highly specific and sensitive with excellent accuracy, reproducibility and repeatability/precision. Concordant results for identification of SNVs and indels were obtained from specimens with DNA input of 2-3 ng, tissue with 10% neoplastic cellularity and variant allelic frequencies of 2.5%-3%. Over 99% of the target areas are shown to achieve at least 500X coverage when parsed through two bioinformatics pipelines. With over 2000 clinical specimens analysed, the success of the panel for reporting of results is 95.3% CONCLUSIONS: The advanced technology enables accurate identification of clinically relevant variants with uniformity of coverage and an impressive turn-around-time. The overall workflow and cost-effectiveness provide added value.

Benchmarking bioinformatics approaches for tumour mutational burden evaluation from a large cancer panel against whole-exome sequencing.

Tumour mutational burden (TMB) is used to predict response to immunotherapies. Although several groups have proposed calculation methods for TMB, a clear consensus has not yet emerged. In this study, we explored TMB calculation approaches with a 586-gene cancer panel (1.75 Mb) benchmarked to TMB measured by whole-exome sequencing (WES), using 30 samples across a range of tumour types. We explored variant allelic fraction (VAF) cut-offs of 5% and 10%, population database filtering at 0.001, 0.0001 and 0.000025, as well as different combinations of synonymous, insertion/deletion and intronic (splice site) variants, as well as exclusion of hotspot mutations, and examined the effect on TMB correlation. Good correlation (Spearman, range 0.66-0.78) between WES and panel TMB was seen across all methods evaluated. Each method of TMB calculation evaluated showed good positive per cent agreement and negative per cent agreement using 10 mutations/Mb as a cut-off, suggesting that multiple TMB calculation approaches may yield comparable results.

Enhanced primary care after hospitalization: General practitioner, pharmacist and patient feedback from the REMAIN HOME trial.

BACKGROUND: Pharmacist and general practitioner (GP) collaborative models of care are continuing to evolve in the Australian primary care setting. The REMAIN HOME study investigated whether a pharmacist integrated into 14 different primary care teams in general practice (the "practice pharmacist model") reduces readmission to hospital for patients prescribed five or more long term medicines or high risk comorbidities. The aim of this paper is to describe the attitudes of GPs, patients, and practice pharmacists towards this model of pharmacist and GP collaboration. METHODS: To explore the views and opinions about the model of care (pharmacist integration into general practice), participating GPs were invited to complete a survey that included the 13-item validated Attitudes Toward Collaboration Instrument for GPs (ATCI-GP) one month after the pharmacist had been integrated into the practice. Survey instruments were also created for patients and pharmacist participating in the intervention. These were deployed after the initial consultation and at the end of the intervention period respectively, to elicit each stakeholders' views and experiences of the service. Data were analysed using descriptive statistics. RESULTS: In total, 48 GPs, 43/101 patients (43%) and 11/13 practice pharmacists (85%) completed the survey. The majority of GPs strongly agreed or agreed with all statements of the ATCI-GP, indicating support for the practice-integrated pharmacist model. Most patients agreed that there was a role for a pharmacist in their general practice (n = 28, 76%), and that they would like to see the pharmacist again (n = 34, 79%). Pharmacists indicated that they enjoyed the role (n = 11, 91%) and found the position professionally satisfying (n = 9, 82%). Most pharmacists agreed that co-location (inside the general practice itself, rather than in a co-located pharmacy) was beneficial (n = 8, 73%) and all pharmacists (100%) acknowledged the benefits of having access to patient medical records. Free text comments from GPs were enthusiastic overall, although some concerns about the financial viability of the model in the current setting were raised. The primary limitation of the study is the anonymous nature of the survey, meaning clustering of responses across the 14 sites could not be determined. CONCLUSIONS: A practice pharmacist model of care in the Australian primary care setting appears to be accepted by GPs, patients and practice pharmacists and provides promising evidence that this model of care is likely to be well accepted if implemented more broadly in the Australian healthcare setting, provided that it can be appropriately remunerated.

Mapping Australian pharmacy school curricula for content related to pharmacogenomics.

Background: Pharmacogenomics (PGx) is a rapidly growing field which promises to deliver personalized, more effective medications tailored to genetic information. Although the pharmacy profession is expected to lead the translation of pharmacogenomics into widespread clinical implementation, there is a reported lack of preparedness among its members. Assessing pharmacogenomic-related training in Australian pharmacy program curricula may highlight educational gaps and provide guidance for curricula revision. Objective: To examine pharmacogenomic content in Australian tertiary pharmacy program curricula. Methods: We reviewed the curriculum of 22 Australian registrable pharmacy degrees, including 16 Bachelors of Pharmacy programs (with or without honors) and six Masters of Pharmacy programs, for content related to pharmacogenomics and genetics. This was done by screening the publicly available electronic course profiles on each institution's website and searching for key terms such as "pharmacogenomics," "pharmacogenetics," "genes," and "genetics". Three mapping activities were completed to assess the breadth and depth of pharmacogenomic training according to; 1. Bloom's taxonomy, 2. Author-assigned domains comprising; Enabling science, Translational science and Clinical implementation, and 3. Pharmacogenomic competencies from the National Human Genome Research Institute (NHGRI). Results: A total of 18 (82%) pharmacy registrable degree programs incorporated pharmacogenomics and/or genetics in their curricula. Four programs (18%) offered standalone PGx courses and 10 (45%) contained integrated PGx content in other science-related courses (i.e. pharmaceutical biology, biochemistry, microbiology etc.). Mapping activities showed that most learning objectives related to the "Understand" level of Bloom's taxonomy (61%), the "Basic Genetic Concepts" domain of NHGRI's competencies (64%) and "Enabling science" (84%). Conclusions: Most Australian pharmacy registrable degrees have incorporated pharmacogenomic content in their curricula however, the scope of training is limited. Revisions to course curricula should be made to incorporate additional education with a focus on application-based training of clinical pharmacogenomics.

A multimodal intervention to optimise antimicrobial use in residential aged care facilities (ENGAGEMENT): protocol for a stepped-wedge cluster randomised trial.

BACKGROUND: Inappropriate antibiotic use can cause harm and promote antimicrobial resistance, which has been declared a major health challenge by the World Health Organization. In Australian residential aged care facilities (RACFs), the most common indications for antibiotic prescribing are for infections of the urinary tract, respiratory tract and skin and soft tissue. Studies indicate that a high proportion of these prescriptions are non-compliant with best prescribing guidelines. To date, a variety of interventions have been reported to address inappropriate prescribing and overuse of antibiotics but with mixed outcomes. This study aims to identify the impact of a set of sustainable, multimodal interventions in residential aged care targeting three common infection types. METHODS: This protocol details a 20-month stepped-wedge cluster-randomised trial conducted across 18 RACFs (as 18 clusters). A multimodal multi-disciplinary set of interventions, the 'AMS ENGAGEMENT bundle', will be tailored to meet the identified needs of participating RACFs. The key elements of the intervention bundle include education for nurses and general practitioners, telehealth support and formation of an antimicrobial stewardship team in each facility. Prior to the randomised sequential introduction of the intervention, each site will act as its own control in relation to usual care processes for antibiotic use and stewardship. The primary outcome for this study will be antibiotic consumption measured using defined daily doses (DDDs). Cluster-level rates will be calculated using total occupied bed numbers within each RACF during the observation period as the denominator. Results will be expressed as rates per 1000 occupied bed days. An economic analysis will be conducted to compare the costs associated with the intervention to that of usual care. A comprehensive process evaluation will be conducted using the REAIM Framework, to enable learnings from the trial to inform sustainable improvements in this field. DISCUSSION: A structured AMS model of care, incorporating targeted interventions to optimise antimicrobial use in the RACF setting, is urgently needed and will be delivered by our trial. The trial will aim to empower clinicians, residents and families by providing a robust AMS programme to improve antibiotic-related health outcomes. TRIAL REGISTRATION: US National Library of Medicine Clinical Trials.gov ( NCT04705259 ). Prospectively registered in 12th of January 2021.