The Association Between Short-Acting ß2-Agonist Over-Prescription, and Patient-Reported Acquisition and Use on Asthma Control and Exacerbations: Data from Australia.

INTRODUCTION: In Australia, short-acting ß2-agonists (SABA) are available both over the counter (OTC) and on prescription. This ease of access may impact SABA use in the Australian population. Our aim was to assess patterns and outcome associations of prescribed, acquired OTC and reported use of SABA by Australians with asthma. METHODS: This was a cross-sectional study, using data derived from primary care electronic medical records (EMRs) and patient completed questionnaires within Optimum Patient Care Research Database Australia (OPCRDA). A total of 720 individuals aged ≥ 12 years with an asthma diagnosis in their EMRs and receiving asthma therapy were included. The annual number of SABA inhalers authorised on prescription, acquired OTC and reported, and the association with self-reported exacerbations and asthma control were investigated. RESULTS: 92.9% (n = 380/409) of individuals issued with SABA prescription were authorised ≥ 3 inhalers annually, although this differed from self-reported usage. Of individuals reporting SABA use (n = 546) in the last 12 months, 37.0% reported using ≥ 3 inhalers. These patients who reported SABA overuse experienced 2.52 (95% confidence interval [CI] 1.73-3.70) times more severe exacerbations and were 4.51 times (95% CI 3.13-6.55) more likely to have poor asthma control than those who reported using 1-2 SABA inhalers. Patients who did not receive SABA on prescription (43.2%; n = 311/720) also experienced 2.71 (95% CI 1.07-7.26) times more severe exacerbations than those prescribed 1-2 inhalers. Of these patients, 38.9% reported using OTC SABA and other prescription medications, 26.4% reported using SABA OTC as their only asthma medication, 13.2% were prescribed other therapies but not SABA OTC and 14.5% were not using any medication. CONCLUSION: Both self-reported SABA overuse and zero SABA prescriptions were associated with poor asthma outcomes. The disconnect between prescribing authorisation, OTC availability and actual use, make it difficult for clinicians to quantify SABA use.

General practitioner assessment and management of insomnia in adults.

BACKGROUND: Sleep disturbance is among the most prevalent presentations in Australian general practice. Insomnia, the most common sleep disorder, is associated with impaired daytime, social and occupational function, reduced quality of life and substantially increased risk of future depression. Guidelines from Australian and international general practice, sleep and medical societies strongly recommend cognitive behavioural therapy for insomnia (CBT-i) as the first-line treatment for chronic insomnia. This is because CBT-i targets the underlying causes of insomnia, results in sustained improvements and commonly improves comorbid conditions such as depression and pain. OBJECTIVE: This article aims to provide an overview of evidence-based assessment, management and referral options for insomnia in Australian general practice. DISCUSSION: Access to brief insomnia assessment and evidenced-based treatments are becoming increasingly available to Australian general practitioners. CBT-i can be delivered through self-guided online programs or by suitably trained general practitioners and psychologists.

Undiagnosed and 'overdiagnosed' COPD using postbronchodilator spirometry in primary healthcare settings: a systematic review and meta-analysis.

BACKGROUND: Despite chronic obstructive pulmonary disease (COPD) being a major global cause of mortality and hospitalisation, it is often undiagnosed or inaccurately diagnosed in clinical settings. OBJECTIVE: To systematically synthesise all peer-reviewed papers from primary healthcare settings that have reported data on: (1) undiagnosed COPD, that is, patients with respiratory symptoms and postbronchodilator airflow obstruction consistent with COPD, without a formal clinician's diagnosis of COPD either documented in health records or reported by patients and (2) 'overdiagnosed COPD', that is, clinician's diagnosis without postbronchodilator airflow obstruction. METHODS: Studies investigating these diagnostic metrics in patients from primary healthcare clinics (according to predefined inclusion/exclusion criteria) were sourced from Medline and Embase and assessed for bias (Johanna Briggs Institute tools for prevalence studies and case series). Meta-analyses of studies of adequate sample size used random effect modelling stratified by risk factor categories. RESULTS: Of 26 eligible articles, 21 cross-sectional studies investigated 3959 cases of spirometry-defined COPD (with or without symptoms), and 5 peer-reviewed COPD case series investigated 7381 patients. The prevalence of spirometry-confirmed COPD without a diagnosis documented in their health records was 14%-26% in studies of symptomatic smokers (N=3). 1 in 4 patients taking inhaled therapies (25% (95% CI 22% to 28%), N=2) and 1 in 6 smokers irrespective of symptoms (16% (95% CI 14% to 18%), N=6) fulfilled diagnostic spirometry criteria but did not report receiving a COPD-related diagnosis. In an adequately powered series of COPD cases documented in primary healthcare records (N=4), only between 50% and 75% of subjects had any airflow obstruction on postbronchodilator spirometry performed by study researchers, therefore, COPD was clinically 'overdiagnosed' in 25%-50% of subjects. DISCUSSION: Although data were heterogeneous and of modest quality, undiagnosed COPD was common in primary healthcare, especially for symptomatic smokers and patients treated with inhaled therapies. In contrast, frequent COPD 'overdiagnosis' may represent treatment of asthma/reversible component or another medical diagnosis. PROSPERO REGISTRATION NUMBER: CRD42022295832.

Detection, characterization, and persistence of Campylobacter hepaticus, the cause of spotty liver disease in layer hens.

A Campylobacter species was first described as the etiological agent of Spotty Liver Disease (SLD) in 2015 and subsequently named as Campylobacter hepaticus in 2016. The bacterium predominantly affects barn and/or free-range hens at peak lay, is fastidious and difficult to isolate, which has impeded elucidation of its sources, means of persistence and transmission. Ten farms from South-Eastern Australia, of which 7 were free range entities participated in the study. A total of 1,404 specimens from layers and 201 from environmental sources, were examined for the presence of C. hepaticus. In this study, our principal findings included the continuing detection of C. hepaticus infection in a flock following an outbreak, indicating a possible transition of infected hens to asymptomatic carriers, that was also characterized by no further occurrence of SLD in the flock. We also report that the first outbreaks of SLD on newly commissioned free-range farms affected layers ranging from 23 to 74 wk of age, while subsequent outbreaks in replacement flocks on these farms occurred during the more conventional peak lay period (23-32 wk of age). Finally, we report that in the on-farm environment, C. hepaticus DNA was detected in layer feces, inert elements such as stormwater, mud, soil, as well as in fauna such as flies, red mites, Darkling beetles, and rats. While in off-farm locations, the bacterium was detected in feces from a variety of wild birds and a canine.

Short-acting ß2-agonist prescription patterns for asthma management in the SABINA III primary care cohort.

Short-acting ß2-agonist (SABA) prescriptions and associated outcomes were assessed in 1440 patients with asthma from the SABA use IN Asthma (SABINA) III study treated in primary care. Data on asthma medications were collected, and multivariable regression models analysed the association of SABA prescriptions with clinical outcomes. Patients (mean age, 47.9 years) were mostly female (68.6%); 58.3% had uncontrolled/partly controlled asthma and 38.8% experienced ≥1 severe exacerbation (reported in 39% of patients with mild asthma). Overall, 44.9% of patients were prescribed ≥3 SABA canisters (over-prescription) and 21.5% purchased SABA over-the-counter. Higher SABA prescriptions (vs 1-2 canisters) were associated with significantly decreased odds of having at least partly controlled asthma (6-9 and 10-12 canisters) and an increased incidence rate of severe exacerbations (10-12 and ≥13 canisters). Findings revealed a high disease burden, even in patients with 'mild' asthma, emphasising the need for local primary care guidelines based on international recommendations.

Pulmonary function testing during SARS-CoV-2: An ANZSRS/TSANZ position statement.

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a joint position paper on pulmonary function testing during coronavirus disease 2019 (COVID-19) in July 2021. A working group was formed via an expression of interest to members of both organizations and commenced work in September 2021. A rapid review of the literature was undertaken, with a 'best evidence synthesis' approach taken to answer the research questions formed. This allowed the working group to accept findings of prior relevant reviews or societal document where appropriate. The advice provided is for providers of pulmonary function tests across all settings. The advice is intended to supplement local infection prevention and state, territory or national directives. The working group's key messages reflect a precautionary approach to protect the safety of both healthcare workers (HCWs) and patients in a rapidly changing environment. The decision on strategies employed may vary depending on local transmission and practice environment. The advice is likely to require review as evidence grows and the COVID-19 pandemic evolves. While this position statement was contextualized specifically to the COVID-19 pandemic, the working group strongly advocates that any changes to clinical/laboratory practice, made in the interest of optimizing the safety and well-being of HCWs and patients involved in pulmonary function testing, are carefully considered in light of their potential for ongoing use to reduce transmission of other droplet and/or aerosol borne diseases.

Characterisation of the Australian Adult Population Living with Asthma: Severe - Exacerbation Frequency, Long-Term OCS Use and Adverse Effects.

Introduction: Asthma poses a significant burden for the Australian population. Understanding severe exacerbation rates, and steroid-related burden for adults diagnosed with asthma stands to offer insights into how this could be reduced. Methods: Electronic medical records (EMR) and questionnaires from the Optimum Patient Care Research Database Australia (OPCRDA) were utilised retrospectively. OPCRDA is a real-world database with >800,000 medical records from Australian primary care practices. Outcomes were severe asthma exacerbations in Australian adults, over a 12-month period, stratified by Global Initiative for Asthma (GINA) treatment intensity steps, and steroid associated comorbidities. Results: Of the 7868 adults treated for asthma, 19% experienced at least one severe exacerbation in the last 12-months. Severe exacerbation frequency increased with treatment intensity (≥1 severe exacerbation GINA 1 13%; GINA 4 23%; GINA 5a 33% and GINA 5b 28%). Questionnaire participants reported higher rates of severe exacerbations than suggested from their EMR (32% vs 23%) especially in steps 1, 4 and 5. Patients repeatedly exposed to steroids had an increased risk of osteoporosis (OR 1.95, 95% CI 1.43-2.66) and sleep apnoea (OR 1.78, 95% CI 1.30-2.46). Conclusion: The Australian population living with GINA 1, 4, 5a and 5b asthma have high severe exacerbation rates and steroid-related burden, especially when compared to other first world countries, with these patients needing alternative strategies or possibly specialist assessment to better manage their condition.

Ten-year prediction model for post-bronchodilator airflow obstruction and early detection of COPD: development and validation in two middle-aged population-based cohorts.

BACKGROUND: Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention. OBJECTIVE: To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile). SETTING: General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively. PARTICIPANTS: For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnaire and spirometry/smoking data, respectively (n=1407). STATISTICAL METHOD: Risk-prediction models were developed using randomForest then externally validated. RESULTS: Area under the receiver operating characteristic curve (AUCROC) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUCROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40-49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if she had quit after age 43. CONCLUSION: This novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age.

Elevation of Condensed Tannins in the Leaves of Ta-MYB14-1 White Clover (Trifolium repens L.) Outcrossed with High Anthocyanin Lines.

Condensed tannins (CT) are highly desirable in forage as they sequester dietary protein and reduce bloat and methane emissions in ruminants. However, the widely used forage legume white clover (Trifolium repens) only produces CTs in flowers and trichomes and at levels too low to achieve therapeutic effects. Genetic transformation with transcription factor Ta-MYB14-1 from Trifolium arvense was effective in inducing CTs to 0.6% of leaf dry matter. CT synthesis has been elevated further by crossing the primary white clover transgenic line with wild type genotypes producing the related phenylpropanoids, anthocyanins. CT levels in leaves were highest under the anthocyanin leaf marks associated with the "red midrib" trait; however, there was no evidence for CT accumulation in leaf sections with the "red V" anthocyanin marking. Ta-MYB14-1 was stably inherited in two generations of crosses, and T2 progeny produced up to 3.6-fold higher CTs than the T0 parent. The profile of small CT oligomers such as dimers and trimers was consistent in T0, T1, T2, and BC2 progeny and consisted predominantly of prodelphinidins (PD), with lesser amounts of procyanidins (PC) and mixed PC:PD oligomers.

Effects of the Spirometry Learning Module on the knowledge, confidence, and experience of spirometry operators.

Our study measures effects of the Spirometry Learning Module (SLM) on health-care professionals' knowledge of spirometry test quality and perceived confidence, experience, and understanding of spirometry measurements and interpretation. Professionals from both primary and hospital-based settings enrolled in the SLM, a training model focusing on spirometry test performance and interpretation, including an online interactive learning component and a face-to-face workshop. Participants were asked to submit patient spirometry assessment worksheets for feedback on quality and interpretation. Data were collected at baseline, SLM completion (20 weeks), and 12 months after SLM completion. Knowledge of spirometry test quality was evaluated with questions relating to five case-based assessments of common spirometric patterns. Perceived confidence, experience, and knowledge in test performance were measured using a 7-point Likert scale. The Friedman test combined with post hoc analyses were used to analyse differences between baseline, 20-week, and 12-month post completion. Qualitative interviews were performed to assess reasons for non-completion. Of the 90 participants enrolled in the SLM and consented to research, 48 completed the 20-week measurement and 11 completed the 12-month measurement. Statistically significant improvements were detected in all outcomes in participants who completed the SLM to 20-week and 12-month follow-up assessments (all p values < 0.01). Barriers to completion were limited access to patients requiring spirometry, high clinic workload, and having a different spirometer at the workplace compared to the one used during SLM demonstrations. Our data suggest that participants' confidence, experience, and knowledge regarding spirometry may improve through SLM completion.

Breaking Free: The Genomics of Allopolyploidy-Facilitated Niche Expansion in White Clover.

The merging of distinct genomes, allopolyploidization, is a widespread phenomenon in plants. It generates adaptive potential through increased genetic diversity, but examples demonstrating its exploitation remain scarce. White clover (Trifolium repens) is a ubiquitous temperate allotetraploid forage crop derived from two European diploid progenitors confined to extreme coastal or alpine habitats. We sequenced and assembled the genomes and transcriptomes of this species complex to gain insight into the genesis of white clover and the consequences of allopolyploidization. Based on these data, we estimate that white clover originated ∼15,000 to 28,000 years ago during the last glaciation when alpine and coastal progenitors were likely colocated in glacial refugia. We found evidence of progenitor diversity carryover through multiple hybridization events and show that the progenitor subgenomes have retained integrity and gene expression activity as they traveled within white clover from their original confined habitats to a global presence. At the transcriptional level, we observed remarkably stable subgenome expression ratios across tissues. Among the few genes that show tissue-specific switching between homeologous gene copies, we found flavonoid biosynthesis genes strongly overrepresented, suggesting an adaptive role of some allopolyploidy-associated transcriptional changes. Our results highlight white clover as an example of allopolyploidy-facilitated niche expansion, where two progenitor genomes, adapted and confined to disparate and highly specialized habitats, expanded to a ubiquitous global presence after glaciation-associated allopolyploidization.

Characterization of Proanthocyanidins from Seeds of Perennial Ryegrass (Lolium perenne L.) and Tall Fescue (Festuca arundinacea) by Liquid Chromatography-Mass Spectrometry.

Perennial ryegrass (Lolium perenne) and tall fescue (Festuca arundinacea) are forage species of the grass family (Poaceae) that are key components of temperate pasture-based agricultural systems. Proanthocyanidins (PAs) are oligomeric flavonoids that, when provided as part of a farm animal's diet, have been reported to improve animal production and health. Up to now, forage grasses have been deemed not to produce PAs. This paper reports for the first time the detection of polymerized PAs in aqueous methanolic extracts of seed tissue of both perennial ryegrass and tall fescue, using LC-MS/MS. We have determined the structure of the PAs to be trans-flavan-3-ol-based, consisting predominately of afzelechin and catechin and linked primarily by B-type bonds. Investigations into the leaf tissue of both species failed to detect any PAs. This discovery opens the possibility of using genetic engineering tools to achieve tannin accumulation in leaf tissue of perennial ryegrass and tall fescue.

Asthma control in general practice -- GP and patient perspectives compared.

BACKGROUND: How general practitioners (GPs) and patients perceive asthma control, and concordance between these perceptions, may influence asthma management and medication adherence. The aims of this study were to determine asthma prevalence in adult patients, measure patient asthma control and the correlation between GP and patient perceptions of asthma control or impact. METHODS: A Supplementary Analysis of Nominated Data (SAND) sub-study of the Bettering the Evaluation and Care of Health (BEACH) program surveyed 2563 patients from 103 GPs. Asthma control was measured using the Asthma Control Questionnaire 5-item version (ACQ-5), and medication adherence by patient self-report. Survey procedures in SAS software and Pearson's correlation statistics were used. RESULTS: Asthma prevalence was 12.7% (95% confidence interval: 10.9-14.5), with good correlation between GP and patient perceptions of asthma control/impact, and with raw ACQ-5 scores. Grouped ACQ-5 scores showed higher levels of uncontrolled asthma. Medication adherence was sub-optimal. DISCUSSION: The ACQ-5 questions are useful for assessing asthma control, for prompting medication reviews, and for reinforcing benefits of medication compliance to improve long-term asthma control.

An integrated genetic linkage map for white clover (Trifolium repens L.) with alignment to Medicago.

BACKGROUND: White clover (Trifolium repens L.) is a temperate forage legume with an allotetraploid genome (2n=4×=32) estimated at 1093 Mb. Several linkage maps of various sizes, marker sources and completeness are available, however, no integrated map and marker set has explored consistency of linkage analysis among unrelated mapping populations. Such integrative analysis requires tools for homoeologue matching among populations. Development of these tools provides for a consistent framework map of the white clover genome, and facilitates in silico alignment with the model forage legume, Medicago truncatula. RESULTS: This is the first report of integration of independent linkage maps in white clover, and adds to the literature on methyl filtered GeneThresher®-derived microsatellite (simple sequence repeat; SSR) markers for linkage mapping. Gene-targeted SSR markers were discovered in a GeneThresher® (TrGT) methyl-filtered database of 364,539 sequences, which yielded 15,647 SSR arrays. Primers were designed for 4,038 arrays and of these, 465 TrGT-SSR markers were used for parental consensus genetic linkage analysis in an F1 mapping population (MP2). This was merged with an EST-SSR consensus genetic map of an independent population (MP1), using markers to match homoeologues and develop a multi-population integrated map of the white clover genome. This integrated map (IM) includes 1109 loci based on 804 SSRs over 1274 cM, covering 97% of the genome at a moderate density of one locus per 1.2 cM. Eighteen candidate genes and one morphological marker were also placed on the IM. Despite being derived from disparate populations and marker sources, the component maps and the derived IM had consistent representations of the white clover genome for marker order and genetic length. In silico analysis at an E-value threshold of 1e-20 revealed substantial co-linearity with the Medicago truncatula genome, and indicates a translocation between T. repens groups 2 and 6 relative to M. truncatula. CONCLUSIONS: This integrated genetic linkage analysis provides a consistent and comprehensive linkage analysis of the white clover genome, with alignment to a model forage legume. Associated marker locus information, particularly the homoeologue-specific markers, offers a new resource for forage legume research to enable genetic analysis and improvement of this forage and grassland species.

Expression of the R2R3-MYB transcription factor TaMYB14 from Trifolium arvense activates proanthocyanidin biosynthesis in the legumes Trifolium repens and Medicago sativa.

Proanthocyanidins (PAs) are oligomeric flavonoids and one group of end products of the phenylpropanoid pathway. PAs have been reported to be beneficial for human and animal health and are particularly important in pastoral agricultural systems for improved animal production and reduced greenhouse gas emissions. However, the main forage legumes grown in these systems, such as Trifolium repens and Medicago sativa, do not contain any substantial amounts of PAs in leaves. We have identified from the foliar PA-accumulating legume Trifolium arvense an R2R3-MYB transcription factor, TaMYB14, and provide evidence that this transcription factor is involved in the regulation of PA biosynthesis in legumes. TaMYB14 expression is necessary and sufficient to up-regulate late steps of the phenylpropanoid pathway and to induce PA biosynthesis. RNA interference silencing of TaMYB14 resulted in almost complete cessation of PA biosynthesis in T. arvense, whereas Nicotiana tabacum, M. sativa, and T. repens plants constitutively expressing TaMYB14 synthesized and accumulated PAs in leaves up to 1.8% dry matter. Targeted liquid chromatography-multistage tandem mass spectrometry analysis identified foliar PAs up to degree of polymerization 6 in leaf extracts. Hence, genetically modified M. sativa and T. repens plants expressing TaMYB14 provide a viable option for improving animal health and mitigating the negative environmental impacts of pastoral animal production systems.

Microbiological contamination of spirometers - an exploratory study in general practice.

BACKGROUND: Spirometry is an important tool when diagnosing chronic respiratory conditions in general practice. However, the equipment may harbour pathogenic micro-organisms and cross-transmission of aerolised pathogens could occur if hygiene measures are insufficient. METHODS: We assessed microbiological contamination in 16 spirometers from a convenience sample of South Australian general practices. Results We found potentially relevant microbiological contamination in three spirometers: two Pseudomonas spp.; one coagulase negative Staphylococcus sp. and one Alcaligenes sp. Although the three practices concerned all reported to have a written spirometer cleaning protocol in place, the frequency of spirometer disinfection did not match the manufacturers' DISCUSSION: Despite the small size of our study sample, we found potentially relevant microbiological contamination in 3 out of 16 spirometers from metropolitan general practices. The potential hazard of spirometers as reservoirs of microorganisms stresses the need for stricter attention to hygiene measures for spirometer maintenance in general practices.