In vitro reminiscence: uterine programming in vivo affects respective luminal epithelial cells function in vitro†.

In cattle, the endometrium during diestrus and early pregnancy displays cellular responses that are consequences of prior, transient stimuli. Goal was to establish a model to study cellular memory in the endometrium. The hypothesis is that stimuli given to endometrium in vivo are retained as a cellular memory that remains after bovine uterine epithelial cells (BUECs) are isolated, cultured, and further stimulated in vitro. Objectives were to measure BUEC proliferation/migration and responsiveness to recombinant bovine Interferon-tau (rbIFNT) in vitro: among cows that showed estrus (experiment 1 [Exp1]), cows that became or not pregnant to artificial insemination (Exp2), cows that received or not supplemental progesterone (P4; Exp3) and cows that received or not a COX-1/2 inhibitor (Exp4). Only cows that displayed estrus were included in studies. For all experiments endometrial cytology was collected 4 days after estrus, BUECs were cultured, propagated, and submitted to rbIFNT treatment and an in vitro scratch assay. In Exp1, different cows spontaneously grouped according to proliferative/migratory capacity and responsiveness to rbIFNT of their respective BUECs. In Exp2, BUECs from pregnant cows showed greater rbIFNT responsiveness and cellular proliferation. In Exp3, BUECs from cows supplemented with P4 presented inhibited proliferation and increased expression of RSAD2. In Exp4, Flunixin Meglumine modified rbIFNT responsiveness of BUECs in an IFN-signaling pathway-specific manner. In conclusion, physiological and pharmacological stimuli received by the endometrium in vivo were retained as cellular memory in BUECs, persisted in culture, and changed BUEC proliferation/migration and responsiveness to rbIFNT, which are characteristics associated with fertility in cattle.

Neighbour-induced changes in root exudation patterns of buckwheat results in altered root architecture of redroot pigweed.

Roots are crucial in plant adaptation through the exudation of various compounds which are influenced and modified by environmental factors. Buckwheat root exudate and root system response to neighbouring plants (buckwheat or redroot pigweed) and how these exudates affect redroot pigweed was investigated. Characterising root exudates in plant-plant interactions presents challenges, therefore a split-root system which enabled the application of differential treatments to parts of a single root system and non-destructive sampling was developed. Non-targeted metabolome profiling revealed that neighbour presence and identity induces systemic changes. Buckwheat and redroot pigweed neighbour presence upregulated 64 and 46 metabolites, respectively, with an overlap of only 7 metabolites. Root morphology analysis showed that, while the presence of redroot pigweed decreased the number of root tips in buckwheat, buckwheat decreased total root length and volume, surface area, number of root tips, and forks of redroot pigweed. Treatment with exudates (from the roots of buckwheat and redroot pigweed closely interacting) on redroot pigweed decreased the total root length and number of forks of redroot pigweed seedlings when compared to controls. These findings provide understanding of how plants modify their root exudate composition in the presence of neighbours and how this impacts each other's root systems.

Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE): protocol for a helix-counterbalanced randomised controlled trial.

INTRODUCTION: Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia's new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. METHODS AND ANALYSIS: The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. DISCUSSION: The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 - retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx .

Information theory and machine learning illuminate large-scale metabolomic responses of Brachypodium distachyon to environmental change.

Plant responses to environmental change are mediated via changes in cellular metabolomes. However, <5% of signals obtained from liquid chromatography tandem mass spectrometry (LC-MS/MS) can be identified, limiting our understanding of how metabolomes change under biotic/abiotic stress. To address this challenge, we performed untargeted LC-MS/MS of leaves, roots, and other organs of Brachypodium distachyon (Poaceae) under 17 organ-condition combinations, including copper deficiency, heat stress, low phosphate, and arbuscular mycorrhizal symbiosis. We found that both leaf and root metabolomes were significantly affected by the growth medium. Leaf metabolomes were more diverse than root metabolomes, but the latter were more specialized and more responsive to environmental change. We found that 1 week of copper deficiency shielded the root, but not the leaf metabolome, from perturbation due to heat stress. Machine learning (ML)-based analysis annotated approximately 81% of the fragmented peaks versus approximately 6% using spectral matches alone. We performed one of the most extensive validations of ML-based peak annotations in plants using thousands of authentic standards, and analyzed approximately 37% of the annotated peaks based on these assessments. Analyzing responsiveness of each predicted metabolite class to environmental change revealed significant perturbations of glycerophospholipids, sphingolipids, and flavonoids. Co-accumulation analysis further identified condition-specific biomarkers. To make these results accessible, we developed a visualization platform on the Bio-Analytic Resource for Plant Biology website (https://bar.utoronto.ca/efp_brachypodium_metabolites/cgi-bin/efpWeb.cgi), where perturbed metabolite classes can be readily visualized. Overall, our study illustrates how emerging chemoinformatic methods can be applied to reveal novel insights into the dynamic plant metabolome and stress adaptation.

Orthology-based analysis helps map evolutionary diversification and predict substrate class use of BAHD acyltransferases.

Large enzyme families catalyze metabolic diversification by virtue of their ability to use diverse chemical scaffolds. How enzyme families attain such functional diversity is not clear. Furthermore, duplication and promiscuity in such enzyme families limits their functional prediction, which has produced a burgeoning set of incompletely annotated genes in plant genomes. Here, we address these challenges using BAHD acyltransferases as a model. This fast-evolving family expanded drastically in land plants, increasing from one to five copies in algae to approximately 100 copies in diploid angiosperm genomes. Compilation of >160 published activities helped visualize the chemical space occupied by this family and define eight different classes based on structural similarities between acceptor substrates. Using orthologous groups (OGs) across 52 sequenced plant genomes, we developed a method to predict BAHD acceptor substrate class utilization as well as origins of individual BAHD OGs in plant evolution. This method was validated using six novel and 28 previously characterized enzymes and helped improve putative substrate class predictions for BAHDs in the tomato genome. Our results also revealed that while cuticular wax and lignin biosynthetic activities were more ancient, anthocyanin acylation activity was fixed in BAHDs later near the origin of angiosperms. The OG-based analysis enabled identification of signature motifs in anthocyanin-acylating BAHDs, whose importance was validated via molecular dynamic simulations, site-directed mutagenesis and kinetic assays. Our results not only describe how BAHDs contributed to evolution of multiple chemical phenotypes in the plant world but also propose a biocuration-enabled approach for improved functional annotation of plant enzyme families.

Next Generation Risk Markers in Preventive Cardio-oncology.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) and cancer are the first and second most common causes of death within the USA. It is well established that a diagnosis of cancer increases risk and predisposes the patient to CVD, and vice versa. Despite these associations, cancer is not yet incorporated into current CVD risk calculators, necessitating additional CV risk markers for improved stratification in this at-risk population. In this review, we consider the utility of breast arterial calcification (BAC), coronary artery calcification (CAC), clonal hematopoiesis of indeterminate potential (CHIP), and cancer and cancer treatment in CVD risk assessment. RECENT FINDINGS: There is evidence supporting the use of BAC, CAC, CHIP, and cancer and cancer treatment for improved CV risk stratification in patients with cancer and those who are being screened for cancer. BAC has been shown to predict CAC, coronary atherosclerotic plaque on coronary CTA, coronary artery stenosis on coronary angiography, and CVD events and accordingly enhances CVD risk stratification beyond the atherosclerotic CVD (ASCVD) risk pooled cohort equation. Additionally, CAC visualized on CT utilized for lung cancer screening, radiation planning, and cancer staging is predictive of coronary artery disease (CAD). Furthermore, CHIP can also be utilized in risk stratification, as the presence of CHIP carries a 40% increase in CV risk independent of traditional CV risk factors. Finally, cancer and many oncologic therapies confer a lifelong increased risk of CVD. We propose an emerging set of tools to be incorporated into the routine continuum of CVD risk assessment in individuals who have been treated for cancer or who are being screened for cancer development. In this review, we discuss BAC, CAC, CHIP, and cancer and cancer treatment as emerging risk markers in cardiovascular health assessment. Their effectiveness in predicting and influencing the burden of CVD will be discussed, along with suggestions on their incorporation into preventive cardio-oncology practice. Future research will focus on short- and long-term CVD outcomes in these populations.

Illuminating the lineage-specific diversification of resin glycoside acylsugars in the morning glory (Convolvulaceae) family using computational metabolomics.

Acylsugars are a class of plant defense compounds produced across many distantly related families. Members of the horticulturally important morning glory (Convolvulaceae) family produce a diverse sub-class of acylsugars called resin glycosides (RGs), which comprise oligosaccharide cores, hydroxyacyl chain(s), and decorating aliphatic and aromatic acyl chains. While many RG structures are characterized, the extent of structural diversity of this class in different genera and species is not known. In this study, we asked whether there has been lineage-specific diversification of RG structures in different Convolvulaceae species that may suggest diversification of the underlying biosynthetic pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed from root and leaf extracts of 26 species sampled in a phylogeny-guided manner. LC-MS/MS revealed thousands of peaks with signature RG fragmentation patterns with one species producing over 300 signals, mirroring the diversity in Solanaceae-type acylsugars. A novel RG from Dichondra argentea was characterized using Nuclear Magnetic Resonance spectroscopy, supporting previous observations of RGs with open hydroxyacyl chains instead of closed macrolactone ring structures. Substantial lineage-specific differentiation in utilization of sugars, hydroxyacyl chains, and decorating acyl chains was discovered, especially among Ipomoea and Convolvulus - the two largest genera in Convolvulaceae. Adopting a computational, knowledge-based strategy, we further developed a high-recall workflow that successfully explained ~72% of the MS/MS fragments, predicted the structural components of 11/13 previously characterized RGs, and partially annotated ~45% of the RGs. Overall, this study improves our understanding of phytochemical diversity and lays a foundation for characterizing the evolutionary mechanisms underlying RG diversification.

A Peer and Volunteer Program for Patients and Their Families in the Pediatric Intensive Care Unit: A Pilot Program Evaluation.

Introduction: Patients in the pediatric intensive care unit (PICU) are at risk of developing long-term morbidities following recovery from their critical illness. One such health outcome is called post-intensive care syndrome (PICS). PICS in pediatrics may be mitigated by interventions that facilitate adjustment to the PICU setting. Methods: The PICU implemented a two-pronged Peer and Volunteer (P/V) Program to help: (a) families adjust to the PICU experience with the support of a peer mentor (PM); and (b) patients receive non-medical interaction from trained volunteers (V). We designed a mixed-methods program evaluation targeting perspectives and feedback from PICU families and healthcare professionals (HCPs). Results: All stakeholder groups agreed that the PICU P/V Program was a valuable resource for PICU patients and their families. HCPs reported that they lack both time and training to provide regular developmental care to patients. However, the P/V Program may influence both families' and HCP's confidence in their ability to offer non-medical interaction to children in the PICU. Discussion: Important initial and on-going strengths and barriers to successful implementation were identified, including the need to clarify roles and intervention scope. The program evaluation served as a change management strategy and also helped to identify both areas for improvement and strategies for on-going sustainability. HCP's exposure to the program and modeling by PMs may have helped HCPs to feel that it is within their job description and capacity to provide emotional support and guidance to families.

Untargeted metabolomics of purple and orange-fleshed sweet potatoes reveals a large structural diversity of anthocyanins and flavonoids.

Anthocyanins are economically valuable phytochemicals of significant relevance to human health. Industrially extracted from multiple fruit and vegetable sources, anthocyanin yield and profiles can vary between sources and growing conditions. In this study, we focused on three purple-fleshed and one orange-fleshed cultivars of sweet potato-a warm-weather, nutritious crop of substantial interest to growers in northern, cooler latitudes-to determine the yield and diversity of anthocyanins and flavonoids. Acidified ethanol extraction of lyophilized roots yielded ~ 800 mg average anthocyanins/100 g dry weight from all three cultivars. UHPLC-DAD-Orbitrap analysis of sweet potato extracts identified 18 high-confidence, mostly acylated peonidin and cyanidin derivatives contributing to > 90% of the total anthocyanin signal. Further assessment of the untargeted Liquid Chromatography-Tandem Mass Spectrometry data using deep learning and molecular networking identified over 350 flavonoid peaks with variable distributions in different sweet potato cultivars. These results provide a novel insight into anthocyanin content of purple-fleshed sweet potatoes grown in the northern latitudes, and reveal the large structural diversity of anthocyanins and flavonoids in this popular crop.

Migration through a Major Andean Ecogeographic Disruption as a Driver of Genetic and Phenotypic Diversity in a Wild Tomato Species.

Evolutionary dynamics at the population level play a central role in creating the diversity of life on our planet. In this study, we sought to understand the origins of such population-level variation in mating systems and defensive acylsugar chemistry in Solanum habrochaites-a wild tomato species found in diverse Andean habitats in Ecuador and Peru. Using Restriction-site-Associated-DNA-Sequencing (RAD-seq) of 50 S. habrochaites accessions, we identified eight population clusters generated via isolation and hybridization dynamics of 4-6 ancestral populations. Detailed characterization of mating systems of these clusters revealed emergence of multiple self-compatible (SC) groups from progenitor self-incompatible populations in the northern part of the species range. Emergence of these SC groups was also associated with fixation of deleterious alleles inactivating acylsugar acetylation. The Amotape-Huancabamba Zone-a geographical landmark in the Andes with high endemism and isolated microhabitats-was identified as a major driver of differentiation in the northern species range, whereas large geographical distances contributed to population structure and evolution of a novel SC group in the central and southern parts of the range, where the species was also inferred to have originated. Findings presented here highlight the role of the diverse ecogeography of Peru and Ecuador in generating population differentiation, and enhance our understanding of the microevolutionary processes that create biological diversity.

"There are ways drug companies will get into DTC decisions": How Australian drug and therapeutics committees address pharmaceutical industry influence.

AIMS: One tool for protecting quality use of medicines in hospitals is a drug and therapeutics committee (DTC) that oversees medicines availability. Pharmaceutical industry marketing to prescribers is associated with less appropriate prescribing and increased costs. There is little data on decision-making practices of DTCs so it is unknown whether or how they might be vulnerable to pharmaceutical industry influence. This project explores DTC decision-making with a focus on how pharmaceutical industry influence on access and use of medicines is identified and managed. METHODS: We used a qualitative methodology with individual interviews of 29 participants who were current or recent members of public hospital DTCs across New South Wales, Australia. Participants included medical, pharmacy and nursing staff and 1 citizen. Committees were linked to specific hospitals or regions, and some were affiliated with paediatric, neonatal, rural or mental health services. RESULTS: Drug committee processes for oversight of medicines in public hospitals are vulnerable to pharmaceutical industry influence at several points. Applications for formulary additions are sometimes initiated and completed by company representatives. Conflict of interest disclosures among applicants and committee members may be incomplete. In some institutions, medicines are available from pharmaceutical companies without committee review, including through free samples and industry-supported medicines access programmes. Participants noticed the presence and impact of pharmaceutical company marketing activities to local clinicians, resulting in increased prescriber demand for products. CONCLUSION: Improved DTC practices and review of hospital policies concerning pharmaceutical marketing activities might preserve the independence of evidence-based decision-making for safe, cost-effective prescribing.

Multidisciplinary perspectives on medication-related decision-making for people with advanced dementia living in long-term care: a critical incident analysis.

PURPOSE: This study aimed to explore medication-related decision-making by health professionals from different disciplines and specialties caring for people with advanced dementia living in long-term care facilities, focusing on dilemmas associated with starting, continuing or deprescribing medications commonly regarded as potentially inappropriate. METHODS: Four focus groups were undertaken, each on a different medication type (antibiotics, lipid-lowering agents, opioids and acetylcholinesterase inhibitors). Transcripts underwent qualitative analysis using line by line inductive coding and then a person-centred framework to highlight themes across medication types. RESULTS: Sixteen participants participated in focus groups. Regardless of medication type or dilemma, results suggested decision-making for residents with advanced dementia should begin with discussing goals of care and engaging with families, and be viewed as an iterative process involving regular monitoring and adjustment. Decision-making was seen as requiring a dialectical approach involving multiple perspectives, with an emphasis on establishing communication between health professionals, family and the person with dementia to better understand goals/preferences for care. CONCLUSION: Inter-professional collaboration enables sharing of clinical experience/expertise, differing disciplinary perspectives and knowledge about the resident. Continuing a medication should be considered an active decision that carries as much responsibility as starting or deprescribing.

Delivering the right information to the right person at the right time to facilitate deprescribing in hospital: a mixed methods multisite study to inform decision support design in Australia.

OBJECTIVES: To inform the design of electronic decision support (EDS) to facilitate deprescribing in hospitals we set out to (1) explore the current processes of in-hospital medicines review, deprescribing and communication of deprescribing decisions with the patient's general practitioner (GP), (2) identify barriers to undertaking these tasks and (3) determine user preferences for EDS. DESIGN: Multimethod, multisite study comprising observations, semistructured interviews and focus groups. SETTING: General medicine, geriatric medicine and rehabilitation wards at six hospitals in two local health districts in Sydney, Australia and primary care practices in one primary healthcare district in Sydney, Australia. PARTICIPANTS: 149 participants took part in observations, interviews and focus groups, including 69 hospital doctors, 13 nurses, 55 pharmacists and 12 GPs. MAIN OUTCOME MEASURES: Observational data on who was involved in medicines review and deprescribing, when medicines review took place, and what artefacts (eg, forms) were used. Participants reported perceptions of medicines review, polypharmacy and deprescribing and preferences for EDS. RESULTS: Deprescribing, undertaken during medicines review, was typically performed by a junior doctor, following a decision to deprescribe by a senior doctor. Key barriers to deprescribing included a perception that deprescribing was not the responsibility of hospital doctors, a lack of confidence among junior doctors and pharmacists in broaching this topic with senior doctors and a lack of patient engagement in the deprescribing process. In designing EDS, the tools, likely to be used by junior doctors, pharmacists and nurses, should be available throughout the hospitalisation and should comprise non-interruptive evidence-based guidance on why and how to deprescribe. CONCLUSIONS: Deprescribing decisions are complex and influenced by multiple factors. The implementation of EDS alone is unlikely to address all barriers identified. To achieve sustained improvements in monitoring of polypharmacy and subsequent deprescribing, a multifaceted intervention is needed.

The Need to Strengthen the Role of the Pharmacist in Sri Lanka: Perspectives.

The role of the pharmacist in healthcare has evolved greatly over the last half-century, from dispensing to providing direct patient-oriented activities not associated with dispensing. However, pharmacist-led healthcare services in Sri Lanka must undergo reform to fully take advantage of their expertise and training in medicine management and related outcomes in Sri Lankan patients. As befits a profession's role development and value, professional and educational standards for pharmacists need ongoing development and growth. Currently, university curricula and continuing professional education in Sri Lanka require further development and optimisation to provide the theoretical and practical knowledge and skills regarding quality use of medicines and patient-oriented care. Furthermore, pharmacists' roles in Sri Lankan hospital and community pharmacist settings need to be recognised and should include the pharmacist as an integral part of the multidisciplinary healthcare team in Sri Lanka. Studies from developed countries and some developing countries have demonstrated that expanded pharmacists' roles have had a significant positive cost-effective impact on the population's health. Therefore, the availability of qualified Sri Lankan pharmacists trained to deliver expanded professional services accompanied by greater pharmacist integration into healthcare delivery is crucially important to ensure quality use of medicines within the Sri Lankan healthcare system and optimise the medication-related needs of Sri Lankans.

Pharmacists' perspectives on medication reviews for long-term care residents with advanced dementia: a qualitative study.

Background Medication reviews by pharmacists have been shown to identify and reduce drug-related problems in long-term care residents. Objective To explore pharmacist perspectives of the Australian Government funded pharmacist-conducted residential medication management review and its role improving the quality and safety of prescribing in long-term care, in particular for those living with advanced dementia. Setting Australian Long-term care pharmacists. Method A qualitative research methodology approach using semi-structured interviews was used, with participants pharmacists with Residential Medication Management Review experience. Interviews were recorded, transcribed and coded utilising a meta-model of Physician-Community Pharmacy Collaboration in medication review. Main outcome measure Pharmacists' perspectives on the Residential Medication Management Review and how to improve the quality of reviews for residents with advanced dementia. Results Fifteen accredited pharmacists participated. The majority believed that the Residential Medication Management Review had the potential to improve the quality and safety of medicines but highlighted systemic issues that worked against collaborative practice. Participants emphasised the importance of three-way collaboration between general practitioners, pharmacists and nursing staff and highlighted key strategies for its optimisation. Conclusion Incorporating avenues for greater communication between team members can improve collaboration between health professionals and ultimately the quality of medication reviews.

A comparative study regarding antibiotic consumption and knowledge of antimicrobial resistance among pharmacy students in Australia and Sri Lanka.

INTRODUCTION: Antimicrobial resistance (AMR) is a major global health challenge. Pharmacists play a key role in the health care setting to support the quality use of medicines. The education and training of pharmacy students have the potential to impact on patterns of antibiotic use in community and hospital settings. The aim of this study was to investigate and compare antibiotic use and knowledge of antibiotics and AMR among undergraduate pharmacy students in Australian and Sri Lankan universities. METHODS: A cross-sectional survey was conducted in Australian and Sri Lankan universities that offer a pharmacy degree. A paper-based survey was utilised in Sri Lanka and an identical survey distributed online among pharmacy students in Australia. Descriptive and comparative data analyses were performed. RESULTS: 476 pharmacy students from 14 universities in Australia and 466 students from 6 universities in SL completed the survey. Participants commonly reported previous antibiotic use [Australia (88%) and Sri Lanka (86%)]. The majority of students [Australia (89%) and Sri Lanka (77%)] reported they obtained antibiotics with a prescription. Australian pharmacy students correctly reported regarding optimal antibiotic use for certain disease conditions when compared to Sri Lankan students (P<0.05). A greater antibiotic knowledge level regarding AMR was found among Australian students compared to Sri Lankan students (p<0.05). CONCLUSION: This study provides an understanding about antibiotic consumption and knowledge on AMR among pharmacy students in a developed country, Australia and a developing country, Sri Lanka. These findings identify possible misconceptions about antibiotics and a lower level of knowledge of AMR amongst Sri Lankan undergraduate pharmacy students. Future research should focus on implementation of a strategic education plan for undergraduate pharmacy students in Sri Lankan universities. The curricula of pharmacy courses in Australian universities may inform such a plan.

Development of Quality Indicators for Cardiac Rehabilitation in Australia: A Modified Delphi Method and Pilot Test.

BACKGROUND: International guidelines recommend cardiac rehabilitation (CR) for secondary prevention of cardiovascular disease, however, it is underutilised and the quality of content and delivery varies widely. Quality indicators (QIs) for CR are used internationally to measure clinical practice performance, but are lacking in the Australian context. This study reports the development of QIs for minimum dataset (MDS) for CR and the results of a pilot test for feasibility and applicability in clinical practice in Australia. METHODS: A modified Delphi method was used to develop initial QIs which involved a consensus approach through a series of face-to-face and teleconference meetings of an expert multidisciplinary panel (n=8), supplemented by an environmental scan of the literature and a multi-site pilot test. RESULTS: Eight (8) QIs were proposed and sent to CR clinicians (n=250) electronically to rate importance, current data collection status, and feasibility of future collection. The top six of these QIs were selected with an additional two key performance indicators from the New South Wales (NSW) Ministry of Health and two QIs from international registers for a draft MDS. The pilot test in 16 sites (938 patient cases) demonstrated median performance of 93% (IQR 47.1-100%). All 10 QIs were retained and one further QI related to diabetes was added for a final draft MDS. CONCLUSIONS: The MDS of 11 QIs for CR provides an important foundation for collection of data to promote the quality of CR nationally and the opportunity to participate in international benchmarking.

Non-prescription sales of antimicrobial agents at community pharmacies in developing countries: a systematic review.

Antimicrobial resistance (AMR) is a global challenge. Developing countries are more vulnerable to the consequences of AMR than developed nations because of complex issues pertaining to the nature of their healthcare systems. Inappropriate antimicrobial drug use and the unrestricted availability of antimicrobial agents in community pharmacies in developing countries can contribute to the emergence of resistant microbes. The aim of this systematic review was to explore the availability of antimicrobial agents without a doctor's prescription in developing countries and to investigate factors that contribute to inappropriate antimicrobial supply in developing countries. The EMBASE, MEDLINE and International Pharmaceutical Abstracts databases were searched for articles published between 1980 and November 2017 describing studies using simulated client (or pseudo-patient) methodology in community pharmacies supplying non-prescription antimicrobial agents. Overall, 50 studies were included in this systematic review. All of the studies involved supply of one or more antimicrobials without a prescription. These studies involved using a hypothetical case presentation or direct product request by a simulated client. The review found non-prescription supply of antimicrobials as reported in 28 developing countries across Asia, Africa, South America, Europe and Middle Eastern regions. Contributing factors for non-prescription antimicrobial supply were poor national medicines regulations, limited availability of qualified pharmacists, commercial pressure on pharmacy staff, consumer demand, inappropriate prescribing practices and lack of awareness of AMR.

Potentially Inappropriate Prescribing in Australian Nursing Home Residents with Advanced Dementia: A Substudy of the IDEAL Study.

BACKGROUND: Prescribing medications for nursing home residents with advanced dementia should focus on optimizing function and comfort, reducing unnecessary harms and aligning care goals with a palliative approach. OBJECTIVE: The aim of the study was to estimate the proportion of Australian nursing home residents with advanced dementia receiving potentially inappropriate medications, and identify those most commonly prescribed and factors associated with their use. DESIGN: Data were collected through retrospective audit of medication charts. SETTING/SUBJECTS: Two hundred eighteen nursing home residents with advanced dementia from 20 nursing homes participated in a cluster-randomized controlled trial of case conferencing (the IDEAL Study) from June 2013 to December 2014. MEASUREMENTS: Inappropriate drug use was defined as medications classified as "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts (PEACE) program criteria. Generalized linear mixed models were used to identify variables predicting use of "never" appropriate medications. RESULTS: Over a quarter (n = 65, 30%) of residents received at least one medication classed as "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%), antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16, 7.3%). Residents who had been at the nursing home for ≤10 months (odds ratio [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41, 95% CI 1.67-17.75) had significantly greater odds of receiving a never appropriate medication compared with residents who had been at the nursing home for >5 years. CONCLUSIONS: Use of potentially inappropriate medications in Australian nursing home residents with advanced dementia is common. A greater understanding of the rationale that underpins prescribing of medications is required.