Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand.

AIMS: The UK Prescribing Safety Assessment was modified for use in Australia and New Zealand (ANZ) as the Prescribing Skills Assessment (PSA). We investigated the implementation, student performance and acceptability of the ANZ PSA for final-year medical students. METHODS: This study used a mixed-method approach involving student data (n = 6440) for 2017-2019 (PSA overall score and 8 domain subscores). Data were also aggregated by medical school and included student evaluation survey results. Quantitative data were analysed using descriptive and multivariate analyses. The pass rate was established by a modified Angoff method. Thematic analyses of open-ended survey comments were conducted. RESULTS: The average pass rate was slightly higher in 2017 (89%) which used a different examination to 2018 (85%) and 2019 (86%). Little difference was identified between schools for the PSA overall performance or domain subscores. There was low intercorrelation between subscores. Most students provided positive feedback about the PSA regarding the interface and clarity of questions, but an average of 35% reported insufficient time for completion. Further, 70% on average felt unprepared by their school curricula for the PSA, which is in part explained by the low prescribing experience; 69% reported completing ≤10 prescriptions during training. CONCLUSION: The ANZ PSA was associated with high pass rates and acceptability, although student preparedness was highlighted as a concern for further investigation. We demonstrate how a collaboration of medical schools can adapt a medical education assessment resource (UK PSA) as a means for fulfilling an unmet need.

NSW Cannabis Medicines Advisory Service preliminary survey results: enquirer perceptions and patient outcomes.

BACKGROUND: In 2018, an innovative, State government-funded cannabis medicines drug information service was established for health professionals in New South Wales (NSW). The NSW Cannabis Medicines Advisory Service (CMAS) provides expert clinical guidance and support to medical practitioners considering prescribing a cannabis medicine to their patient(s). AIMS: This research examines quality assurance and patient outcomes related to enquirers' experience with NSW CMAS. METHODS: Data collection involved an online, anonymous survey with two components. Following a health professional enquiry, quality assurance data were collected about the enquirers' experience with NSW CMAS. The second survey focussed on patient outcomes and provides real-world observational data about cannabis medicines safety and effectiveness across a wide range of indications. RESULTS: Data collection occurred between January 2020 and June 2021. Preliminary analyses were based on 68 quality assurance and 50 patient outcomes survey responses. General practitioners represented the highest proportion of survey responses (n = 33; 49%). The most common enquiry involved 'patient-specific advice' (n = 50; 74%). Patient-specific information provided by the service was mainly used for prescribing decision support (n = 45; 90%). CONCLUSIONS: Preliminary findings highlight the impact of an innovative cannabis medicines drug information service in supporting health professional clinical practice in an area of rapid knowledge translation. Quality assurance data indicate that the service is perceived well by the majority of enquirers. Patient outcomes data across a wide range of indications suggest some effectiveness and a reasonable safety profile for prescribed cannabis medicines for most patients.

Translational hurdles with cannabis medicines.

PURPOSE: Internationally, there has been widespread medical use of cannabis medicines before rigorous evaluations in randomised controlled trials (RCTs). Some advocates of medicinal use of cannabis argue that real-world evidence (RWE) can be a substitute for or at least supplement evidence from RCTs. We explore the utility, limitations and impact of RWE in the translation of cannabis medicines research into clinical practice using the established literature. METHODS: A literature search was performed via Embase and Medline using a diverse range of cannabinoid and RWE search terms. The review provides a snapshot of cannabis medicine RWE initiatives from around the world. RESULTS: Diverse and novel sources of real-world data and RWE include international cannabis registries, surveys, post-marketing data collection and use of electronic or digital health records. The strengths and limitations of using RWE in translational research are highlighted, along with the identification of barriers to RCTs involving cannabis medicines. CONCLUSIONS: RWE promises to play a significant role in the evaluation of cannabis medicines around the world. When used appropriately RWE may complement RCT data by providing valuable insights into cannabis medicine safety and effectiveness. TAKE HOME MESSAGES: It is important that real-world evidence (RWE) is used to complement rather than replace randomised controlled trial (RCT) evidence on cannabis medicines. Technological advances have created the opportunity to explore diverse and novel sources of cannabis medicine RWE. Although RWE may be more reflective of real-world clinical practice, it cannot provide conclusive evidence of the safety and efficacy of cannabis medicines. While acknowledging its limitations, RWE may nonetheless provide some guidance on safety and adverse events of cannabis medicines. RWE has already had a significant impact on the regulation of cannabis medicines.

Vancomycin therapeutic drug monitoring in paediatrics.

AIM: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. METHODS: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. RESULTS: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05-86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0-39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. CONCLUSION: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.

Optimising low-dose methotrexate for rheumatoid arthritis-A review.

Methotrexate at low doses (5-25 mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of variability in concentrations of active polyglutamate metabolites, associated with clinical efficacy and toxicity. Prescribing remains heterogeneous across population groups, disease states and regimens. This review examines current knowledge of dose-response of oral methotrexate in the setting of rheumatoid arthritis, and how this could help inform dosage regimens.

The role of nuclear lamin B1 in cell proliferation and senescence.

Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. These results demonstrate the importance of LB1 in regulating the proliferation and senescence of human diploid cells through a ROS signaling pathway.

The pharmacokinetics and the pharmacodynamics of cannabinoids.

There is increasing interest in the use of cannabinoids for disease and symptom management, but limited information available regarding their pharmacokinetics and pharmacodynamics to guide prescribers. Cannabis medicines contain a wide variety of chemical compounds, including the cannabinoids delta-9-tetrahydrocannabinol (THC), which is psychoactive, and the nonpsychoactive cannabidiol (CBD). Cannabis use is associated with both pathological and behavioural toxicity and, accordingly, is contraindicated in the context of significant psychiatric, cardiovascular, renal or hepatic illness. The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements. As both THC and CBD are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters. An important example is the CBD-mediated inhibition of clobazam metabolism. Pharmacodynamic interactions may occur if cannabis is administered with other central nervous system depressant drugs, and cardiac toxicity may occur via additive hypertension and tachycardia with sympathomimetic agents. More vulnerable populations, such as older patients, may benefit from the potential symptomatic and palliative benefits of cannabinoids but are at increased risk of adverse effects. The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects. Further clinical studies in the actual patient populations for whom prescribing may be considered are needed, to derive a better understanding of these drugs and enhance safe and optimal prescribing.

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects.

There has been a resurgence in interest and use of the cannabis plant for medical purposes. However, an in-depth understanding of plant contaminants and toxin effects on stability of plant compounds and human bioavailability is needed. This systematic review aims to assess current understanding of the contaminants of cannabis and their effect on human health, leading to the identification of knowledge gaps for future investigation. A systematic search of seven indexed biological and biomedical databases and the Cochrane library was undertaken from inception up to December 2017. A qualitative synthesis of filtered results was undertaken after independent assessment for eligibility by two reviewers. The common cannabis contaminants include microbes, heavy metals and pesticides. Their direct human toxicity is poorly quantified but include infection, carcinogenicity, reproductive and developmental impacts. Cannabis dosing formulations and administration routes affect the transformation and bioavailability of contaminants. There may be important pharmacokinetic interactions between the alkaloid active ingredients of cannabis (i.e. phytocannabinoids) and contaminants but these are not yet identified nor quantified. There is significant paucity in the literature describing the prevalence and human impact of cannabis contaminants. Advances in the availability of cannabis globally warrant further research in this area, particularly when being used for patients.

Models of nutrition-focused continuing education programs for nurses: a systematic review of the evidence.

Nurses are well-positioned to provide basic nutrition education and reinforce nutrition messages to patients in hospital and primary care settings. Despite this, nurses may not receive adequate training to provide this service, and there is limited opportunity for nurses to engage in nutrition-focused continuing education (CE). The aim of this review was to determine whether nurse nutrition education results in improved knowledge and practices; and explore which models of CE for nutrition may be most acceptable and effective in practice. Web of Science and Scopus were searched for case-series studies published between 2000 and 2016 that investigated changes in nutrition knowledge of nurses and midwives. Only studies that could transcend to nurses providing patient nutrition education were included. Twelve articles met the eligibility criteria. Articles are explored in terms of mode of delivery, duration of intervention and educational strategies employed. Nutrition CE programs that are delivered face-to-face or by self-directed learning manuals, which utilise active learning strategies, are positively associated with improvements in nutrition knowledge. Web-based CE and self-directed learning may be favourable modes of delivery as they may assist in addressing resource and time contraints.

Predicting drug interactions in addiction treatment.

It is not uncommon to be treating people with addiction who also have significant other health problems, including heart, renal or liver failure, diabetes and vascular disease. These conditions require regular medications to be taken. This can be a problem for people living with addiction and difficult social circumstances affecting compliance, among other issues. Our perspective provides a summary of general pharmacological factors affecting medicine taking in people with addiction problems, to provide a guide for hospital doctors in this setting.

Review of patient satisfaction with services provided by general practitioners in an antenatal shared care program.

BACKGROUND: Antenatal shared care (ANSC) is a model of care in Australia whereby pregnant women are managed by their general practitioner (GP) and an obstetrician at a public antenatal clinic throughout the pregnancy. The aim of this study was to assess pregnant women's satisfaction with the ANSC program and the adequacy of advice provided to pregnant women. METHODS: Women participating in ANSC in the Illawarra region of NSW were invited to complete a satisfaction survey, which included questions on relevant topics discussed with their GP. RESULTS: Most women reported being highly satisfied with the ANSC service. Over half of the women had not received any information about breastfeeding and nutritional supplementation of iodine.

Characterization of a large human transgene following invasin-mediated delivery in a bacterial artificial chromosome.

Bacterial artificial chromosomes (BACs) are widely used in transgenesis, particularly for the humanization of animal models. Moreover, due to their extensive capacity, BACs provide attractive tools to study distal regulatory elements associated with large gene loci. However, despite their widespread use, little is known about the integration dynamics of these large transgenes in mammalian cells. Here, we investigate the post-integration structure of a ~260 kb BAC carrying the cystic fibrosis transmembrane conductance regulator (CFTR) locus following delivery by bacterial invasion and compare this to the outcome of a more routine lipid-based delivery method. We find substantial variability in integrated copy number and expression levels of the BAC CFTR transgene after bacterial invasion-mediated delivery. Furthermore, we frequently observed variation in the representation of different regions of the CFTR transgene within individual cell clones, indicative of BAC fragmentation. Finally, using fluorescence in situ hybridization, we observed that the integrated BAC forms extended megabase-scale structures in some clones that are apparently stably maintained at cell division. These data demonstrate that the utility of large BACs to investigate cis-regulatory elements in the genomic context may be limited by recombination events that complicate their use.

Nutrition advice during pregnancy: do women receive it and can health professionals provide it?

A healthy diet during pregnancy is essential for normal growth and development of the foetus. Pregnant women may obtain nutrition information from a number of sources but evidence regarding the adequacy and extent of this information is sparse. A systematic literature review was conducted to identify sources of nutrition information accessed by pregnant women, their perceived needs for nutrition education, the perceptions of healthcare providers about nutrition education in pregnancy, and to assess the effectiveness of public health programs that aim to improve nutritional practices. The Scopus data base was searched during January, 2013 and in February 2014 to access both qualitative and quantitative studies published between 2002 and 2014 which focused on healthy pregnant women and their healthcare providers in developed countries. Articles were excluded if they focused on the needs of women with medical conditions, including obesity, gestational diabetes or malnutrition. Of 506 articles identified by the search terms, 25 articles were deemed to be eligible for inclusion. Generally, women were not receiving adequate nutrition education during pregnancy. Although healthcare practitioners perceived nutrition education to be important, barriers to providing education to clients included lack of time, lack of resources and lack of relevant training. Further well designed studies are needed to identify the most effective nutrition education strategies to improve nutrition knowledge and dietary behaviours for women during antenatal care.