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Leena R Baghdadi,1 Richard J Woodman,2 E Michael Shanahan,3 Michael D Wiese,4 Arduino A Mangoni5 1Department of Family and Community Medicine, College of Medicine, King Saud University and King Khalid University Hospital, Riyadh, Saudi Arabia; 2Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; 3Department of Rheumatology, College of Medicine and Public Health, Flinders University and Southern Adelaide Local Health Network, Adelaide, SA, Australia; 4School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia; 5Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, SA, Australia Purpose: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. Patients and methods: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months. Results: Majority of the RA patients were homozygotes for the normal allele (CC, n=46) whereas 10 were rs2231142 heterozygotes (AC, n=10). MTXPGs concentrations were non-significantly higher in AC when compared to CC (144.3 vs 116.3 nmol/L packed RBCs, P=0.10). At baseline, the AC group had significantly lower age-adjusted clinical systolic BP (SBP) (P=0.01), 24-hour peripheral SBP (P=0.003), and central SBP (P=0.02) when compared to the CC group. However, AIx and PWV values were not significantly different between the two groups. When data from both visits were combined in a single analysis, and additionally adjusted for visit, gender, body mass index, and Disease Activity Score 28, the trend in SBP differences between-groups persisted but was no longer significant. Conclusion: Future studies are required to test the hypothesis that this genetic polymorphism is associated with lower BP, arterial stiffness, and possibly, cardiovascular risk, in RA patients treated with MTX. Keywords: methotrexate, disease-modifying antirheumatic drugs, blood pressure, augmentation index, rheumatoid arthritis, pulse wave velocity, single-nucleotide polymorphisms, ATP-binding cassette transporters, ABCG2

Cameron J Phillips,1–4 Alice J Wisdom,5 Ross A McKinnon,2,3,6 Richard J Woodman,7 David L Gordon2,8,9 1SA Pharmacy, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia; 2College of Medicine and Public Health, Flinders University, Adelaide, SA 5000, Australia; 3School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia; 4Infectious Diseases and Immunity, Department of Medicine, Imperial College, London W12 0NN, UK; 5SA Pharmacy, Lyell McEwin Hospital, Elizabeth Vale, Adelaide, SA 5112, Australia; 6Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA 5000, Australia; 7Flinders Centre for Epidemiology and Biostatistics, Flinders University, Adelaide, SA 5000, Australia; 8SA Pathology, Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia; 9Division of Medicine, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia Purpose: Vancomycin prescribing requires individualized dosing and monitoring to ensure efficacy, limit toxicity, and minimize resistance. Although there are nationally endorsed guidelines from several countries addressing the complexities of vancomycin dosing and monitoring, there is limited consideration of how to implement these recommendations effectively.Methods: We conducted a systematic search of multiple databases to identify relevant comparative studies describing the impact of interventions of educational meetings, implementation of guidelines, and dissemination of educational material on vancomycin dosing, monitoring, and nephrotoxicity. Effect size was assessed using ORs and pooled data analyzed using forest plots to provide overall effect measures. Results: Six studies were included. All studies included educational meetings. Two studies used implementation of guidance, educational meetings, and dissemination of educational materials, one used guidance and educational meetings, one educational meetings and dissemination of educational materials, and two used educational meetings solely. Effect sizes for individual studies were more likely to be significant for multifaceted interventions. In meta-analysis, the overall effect of interventions on outcome measures of vancomycin dosing was OR 2.50 (95% CI 1.29–4.84); P< 0.01. A higher proportion of sampling at steady-state concentration was seen following intervention (OR 1.95, 95% CI 1.26–3.02; P

Cameron J Phillips,1–3 Nicholas A Wells,4 Marianne Martinello,4 Simon Smith,4 Richard J Woodman,5 David L Gordon2,4 1SA Pharmacy, Flinders Medical Centre, Bedford Park, SA, Australia; 2Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, SA, Australia; 3School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; 4SA Pathology, Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, Australia; 5Flinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Adelaide, SA, Australia Background: Determination of vancomycin minimum inhibitory concentration (MIC) can influence the agent used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. We studied diagnostic accuracy using E-test and VITEK® 2 against a gold standard broth microdilution (BMD) methodology, the correlation between methods, and associations between vancomycin MIC and MRSA phenotype from clinical isolates.Methods: MRSA isolates were obtained from April 2012 to December 2013. Vancomycin MIC values were determined prospectively on all isolates by gradient diffusion E-test and automated VITEK® 2 . The Clinical and Laboratory Standards Institute reference BMD method was performed retrospectively on thawed frozen isolates. Diagnostic accuracy for detecting less susceptible strains was calculated at each MIC cutoff point for E-Test and VITEK® 2 using BMD ≥1 µg/mL as a standard. The correlation between methods was assessed using Spearman’s rho (ρ). The association between MRSA phenotype and MIC for the three methods was assessed using Fisher’s exact test.Results: Of 148 MRSA isolates, all except one (E-test =3 µg/mL) were susceptible to vancomycin (MIC of ≤2 µg/mL) irrespective of methodology. MICs were ≥1.0 µg/mL for 9.5% of BMD, 50.0% for VITEK® 2 , and 27.7% for E-test. Spearman’s ρ showed weak correlations between methods: 0.29 E-test vs VITEK® 2 (P=0.003), 0.27 E-test vs BMD (P=0.001), and 0.31 VITEK® 2 vs BMD (P=0.002). The optimal cutoff points for detecting BMD-defined less susceptible strains were ≥1.0 µg/mL for E-test and VITEK® 2 . E-test sensitivity at this cutoff point was 0.85 and specificity 0.29, while VITEK® 2 sensitivity and specificity were 0.62 and 0.51, respectively. Multiresistant MRSA strains tended to have higher MIC values compared to nonmultiresistant MRSA or epidemic MRSA 15 phenotypes by E-test (Fisher’s exact P

PURPOSE OF REVIEW: This review details the independent effects of purified eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. We report data from the recent literature and our own controlled clinical trials which compared the independent effects of these fatty acids in individuals at increased risk of cardiovascular disease, namely overweight hyperlipidaemic men and treated-hypertensive, type 2 diabetic men and women. We discuss the biological effects of these fatty acids and the potential mechanisms through which they may affect cardiovascular disease risk factors. RECENT FINDINGS: A cardioprotective effect for omega3 fatty acids is supported by prospective studies demonstrating an inverse association between fish intake and coronary heart disease mortality. Data from secondary prevention trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. Clinical trials and experimental studies have shown that omega3 fatty acids have many other potentially important antiatherogenic and antithrombotic effects. Omega-3 fatty acids lower blood pressure and heart rate, improve dyslipidaemia, reduce inflammation, and improve vascular and platelet function. These favourable effects have until recently been primarily attributed to the omega3 fatty acid eicosapentaenoic acid, which is present in large amounts in fish oil. Controlled studies in humans now demonstrate that docosahexaenoic acid, although often present in lower quantities, has equally important anti-arrhythmic, anti-thrombotic and anti-atherogenic effects. SUMMARY: Available evidence strongly suggests that eicosapentaenoic acid and docosahexaenoic acid have differing haemodynamic and anti-atherogenic properties. The effects of the two fatty acids may also differ depending on the target population. [ABSTRACT FROM AUTHOR]

Background: Higher cruciferous vegetable intake is associated with lower cardiovascular disease risk in observational studies. The pathways involved remain uncertain. We aimed to determine whether cruciferous vegetable intake (active) lowers 24-h brachial systolic blood pressure (SBP; primary outcome) compared to root and squash vegetables (control) in Australian adults with mildly elevated BP (SBP 120-160 mmHg inclusive)., Methods: In this randomized, controlled, crossover trial, participants completed two 2-week dietary interventions separated by a 2-week washout. Cruciferous vegetables were compared to root and squash vegetables (~ 300 g/day) consumed with lunch and dinner meals. Participants were blinded to which interventions were the active and control. Adherence was assessed using food diaries and biomarkers (S-methyl cysteine sulfoxide (SMCSO, active) and carotenoids (control)). Twenty-four-hour brachial ambulatory SBP and secondary outcomes were assessed pre- and post each intervention. Differences were tested using linear mixed effects regression., Results: Eighteen participants were recruited (median (IQR) age: 68 (66-70); female: n = 16/18; mean ± SD clinic SBP: 135.9 ± 10.0 mmHg). For both interventions, 72% participants had 100% adherence (IQR: 96.4-100%). SMCSO and carotenoids were significantly different between interventions (mean difference active vs. control SMCSO: 22.93 mg/mL, 95%CI 15.62, 30.23, P < 0.0001; carotenoids: - 0.974 mg/mL, 95%CI - 1.525, - 0.423, P = 0.001). Twenty-four-hour brachial SBP was significantly reduced following the active vs. control (mean difference - 2.5 mmHg, 95%CI - 4.2, - 0.9, P = 0.002; active pre: 126.8 ± 12.6 mmHg, post: 124.4 ± 11.8 mmHg; control pre: 125.5 ± 12.1 mmHg, post: 124.8 ± 13.1 mmHg, n = 17), driven by daytime SBP (mean difference - 3.6 mmHg, 95%CI - 5.4, - 1.7, P < 0.001). Serum triglycerides were significantly lower following the active vs. control (mean difference - 0.2 mmol/L, 95%CI - 0.4, - 0.0, P = 0.047)., Conclusions: Increased intake of cruciferous vegetables resulted in reduced SBP compared to root and squash vegetables. Future research is needed to determine whether targeted recommendations for increasing cruciferous vegetable intake benefits population health., Trial Registration: Clinical trial registry ACTRN12619001294145.  https://www.anzctr.org.au., (© 2024. The Author(s).)

Background: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans., Aim: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension., Methods: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F 2 -isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets., Results: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14 + CD16 - ) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo., Conclusions: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods., Clinical Trial Registry Number: NCT04584372 (ClinicialTrials.gov)., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements included nitrate and nitrite in plasma and saliva; endothelial-dependent and -independent forearm blood flow (FBF) responses to acetylcholine (FBF ACh ) and glyceryltrinitrate (FBF GTN ); and clinic-, home- and 24-hour ambulatory blood pressure. Compared to placebo, plasma and salivary nitrate and nitrite increased at 3H and 4WK POST following nitrate treatment ( P < 0.01), suggesting a functioning nitrate-nitrite-NO pathway in the participants of this study. There were no differences between treatments in FBF ACh and FBF GTN -area under the curve (AUC) ratios [AUC ratios after (3H POST, 4WK POST) compared with before (PRE) the intervention], or 24-hour ambulatory blood pressure or home blood pressure measures ( P > 0.05). These findings do not support the hypothesis that an increased intake of dietary nitrate exerts sustained beneficial effects on FBF or blood pressure in hypertensive older adults, providing important information on the efficacy of nitrate-based interventions for healthy vascular aging. This study was registered under ClinicialTrials.gov (NCT04584372).

Background and Aims: Improving the care of decompensated cirrhosis is a significant clinical challenge. The primary aim of this trial was to assess the efficacy of a chronic disease management (CDM) model to reduce liver-related emergency admissions (LREA). The secondary aims were to assess model effects on quality-of-care and patient-reported outcomes., Approach and Results: The study design was a 2-year, multicenter, randomized controlled study with 1:1 allocation of a CDM model versus usual care. The study setting involved both tertiary and community care. Participants were randomly allocated following a decompensated cirrhosis admission. The intervention was a multifaceted CDM model coordinated by a liver nurse. A total of 147 participants (intervention=75, control=71) were recruited with a median Model for End-Stage Liver Disease score of 19. For the primary outcome, there was no difference in the overall LREA rate for the intervention group versus the control group (incident rate ratio 0.89; 95% CI: 0.53-1.50, p=0.666) or in actuarial survival (HR=1.14; 95% CI: 0.66-1.96, p=0.646). However, there was a reduced risk of LREA due to encephalopathy in the intervention versus control group (HR=1.87; 95% CI: 1.18-2.96, p=0.007). Significant improvement in quality-of-care measures was seen for the performance of bone density (p<0.001), vitamin D testing (p<0.001), and HCC surveillance adherence (p=0.050). For assessable participants (44/74 intervention, 32/71 controls) significant improvements in patient-reported outcomes at 3 months were seen in self-management ability and quality of life as assessed by visual analog scale (p=0.044)., Conclusions: This CDM intervention did not reduce overall LREA events and may not be effective in decompensated cirrhosis for this end point., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The current management of patients with multimorbidity is suboptimal, with either a single-disease approach to care or treatment guideline adaptations that result in poor adherence due to their complexity. Although this has resulted in calls for more holistic and personalized approaches to prescribing, progress toward these goals has remained slow. With the rapid advancement of machine learning (ML) methods, promising approaches now also exist to accelerate the advance of precision medicine in multimorbidity. These include analyzing disease comorbidity networks, using knowledge graphs that integrate knowledge from different medical domains, and applying network analysis and graph ML. Multimorbidity disease networks have been used to improve disease diagnosis, treatment recommendations, and patient prognosis. Knowledge graphs that combine different medical entities connected by multiple relationship types integrate data from different sources, allowing for complex interactions and creating a continuous flow of information. Network analysis and graph ML can then extract the topology and structure of networks and reveal hidden properties, including disease phenotypes, network hubs, and pathways; predict drugs for repurposing; and determine safe and more holistic treatments. In this article, we describe the basic concepts of creating bipartite and unipartite disease and patient networks and review the use of knowledge graphs, graph algorithms, graph embedding methods, and graph ML within the context of multimorbidity. Specifically, we provide an overview of the application of graph theory for studying multimorbidity, the methods employed to extract knowledge from graphs, and examples of the application of disease networks for determining the structure and pathways of multimorbidity, identifying disease phenotypes, predicting health outcomes, and selecting safe and effective treatments. In today's modern data-hungry, ML-focused world, such network-based techniques are likely to be at the forefront of developing robust clinical decision support tools for safer and more holistic approaches to treating older patients with multimorbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Woodman, Koczwara and Mangoni.)

Study Objectives: The sleep apnea multi-level surgery (SAMS) randomized clinical trial showed surgery improved outcomes at 6 months compared to ongoing medical management in patients with moderate or severe obstructive sleep apnea (OSA) who failed continuous positive airway pressure therapy. This study reports the long-term outcomes of the multi-level surgery as a case series., Methods: Surgical participants were reassessed >2 years postoperatively with the same outcomes reported in the main SAMS trial. Primary outcomes were apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS), with secondary outcomes including other polysomnography measures, symptoms, quality of life, and adverse events. Long-term effectiveness (baseline to long-term follow-up [LTFU]) and interval changes (6 month to LTFU) were assessed using mixed effects regression models. Control participants were also reassessed for rate of subsequent surgery and outcomes., Results: 36/48 (75%) of surgical participants were reevaluated (mean (standard deviation)) 3.5 (1.0) years following surgery, with 29 undergoing polysomnography. AHI was 41/h (23) at preoperative baseline and 21/h (18) at follow-up, representing persistent improvement of -24/h (95% CI -32, -17; p < 0.001). ESS was 12.3 (3.5) at baseline and 5.5 (3.9) at follow-up, representing persistent improvement of -6.8 (95% CI -8.3, -5.4; p < 0.001). Secondary outcomes were improved long term, and adverse events were minor. Interval change analysis suggests stability of outcomes. 36/43 (84%) of the control participants were reevaluated, with 25 (69%) reporting subsequent surgery, with symptom and quality of life improvements., Conclusion: Multi-level upper airway surgery improves OSA burden with long-term maintenance of treatment effect in adults with moderate or severe OSA in whom conventional therapy failed., Clinical Trial: Multi-level airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true; ACTRN12614000338662., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The increasing access to health data worldwide is driving a resurgence in machine learning research, including data-hungry deep learning algorithms. More computationally efficient algorithms now offer unique opportunities to enhance diagnosis, risk stratification, and individualised approaches to patient management. Such opportunities are particularly relevant for the management of older patients, a group that is characterised by complex multimorbidity patterns and significant interindividual variability in homeostatic capacity, organ function, and response to treatment. Clinical tools that utilise machine learning algorithms to determine the optimal choice of treatment are slowly gaining the necessary approval from governing bodies and being implemented into healthcare, with significant implications for virtually all medical disciplines during the next phase of digital medicine. Beyond obtaining regulatory approval, a crucial element in implementing these tools is the trust and support of the people that use them. In this context, an increased understanding by clinicians of artificial intelligence and machine learning algorithms provides an appreciation of the possible benefits, risks, and uncertainties, and improves the chances for successful adoption. This review provides a broad taxonomy of machine learning algorithms, followed by a more detailed description of each algorithm class, their purpose and capabilities, and examples of their applications, particularly in geriatric medicine. Additional focus is given on the clinical implications and challenges involved in relying on devices with reduced interpretability and the progress made in counteracting the latter via the development of explainable machine learning., (© 2023. The Author(s).)

The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet ( p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella ( p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures ( p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.

Objectives To explore general practitioners' perspectives on the discharge summaries they receive about their patients who have been discharged from hospital. Methods A survey of general practitioners in the catchment of a major metropolitan South Australian health service consisting of three teaching hospitals was undertaken. Surveys were disseminated electronically and via hardcopy mailout to general practitioners. The 36-question survey focused on five constructs of discharge summaries: accessibility, length and clarity, format, transparency, and medicines content. Results A total of 150 general practitioners responded (response rate, 27.6%). Respondents were vocationally registered (96%), predominately from metropolitan practices (90.2%), and 65.8% were female. Overwhelmingly, 86.7% of general practitioners stated that the optimal time for receipt of discharge summaries was <48 h post-discharge, and 96.6% considered that late arrival of discharge summaries adversely impacts patient care. The ideal length of discharge summaries was reported as <4 pages by 64% of respondents. A large proportion of respondents (84.6%) would like to be notified when their patients are admitted and discharged from hospital, and 82.7% were supportive of patients receiving their own copy of the discharge summary. A total of 76.7% general practitioners reported that they had detected omissions or discrepancies in the discharge summaries. Provision of rationale for medication changes was viewed as important by 86.7%, however, only 29.3% reported that it is always or often communicated. Conclusions General practitioners supported timely receipt, concise length of discharge summary and format refinement to improve the utility and communication of this important clinical handover from hospital to community care.

Objective: The aims of this study were to compare threshold and suprathreshold ictal electroencephalograms (EEGs) in right unilateral (RUL) ultrabrief (UB) electroconvulsive therapy (ECT) and to identify the differences between these EEGs., Methods: This study is a retrospective review of 125 pairs EEGs from titration and subsequent sessions across a 2-year period. All EEGs were independently rated for by 2 assessors using a scale based on qualities of an EEG used to guide ECT treatment dose adequacy, for example, midictal amplitude, regularity, interhemispheric coherence, seizure end point, and postictal suppression. The scores of threshold and suprathreshold EEGs were compared within and between groups based on 2 ECT types, that is, RUL UB ECT and RUL brief pulse (BP) ECT., Results: Paired t tests showed a statistically significant difference in between threshold and suprathreshold EEG scores in RUL UB ECT. There were no statistically significant differences between corresponding scores for RUL UB ECT and RUL BP ECT threshold and suprathreshold EEGs., Conclusions: There is a significant difference between the quality of threshold and suprathreshold EEGs in RUL UB ECT when measured with an EEG rating scale. Visual rating of ictal EEGs is as reliable in discriminating between threshold and suprathreshold seizure in RUL UB ECT as it is in RUL BP ECT., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The biomarker development field within molecular medicine remains limited by the methods that are available for building predictive models. We developed an efficient method for conservatively estimating confidence intervals for the cross validation-derived prediction errors of biomarker models. This new method was investigated for its ability to improve the capacity of our previously developed method, StaVarSel, for selecting stable biomarkers. Compared with the standard cross validation method, StaVarSel markedly improved the estimated generalisable predictive capacity of serum miRNA biomarkers for the detection of disease states that are at increased risk of progressing to oesophageal adenocarcinoma. The incorporation of our new method for conservatively estimating confidence intervals into StaVarSel resulted in the selection of less complex models with increased stability and improved or similar predictive capacities. The methods developed in this study have the potential to improve progress from biomarker discovery to biomarker driven translational research.

Aims: Cardiovascular magnetic resonance (CMR) imaging has a potential role in the evaluation of symptomatic patients with stable troponin elevation; however, its utility remains unexplored. We sought to determine the incremental diagnostic value of CMR in this unique cohort and assess the long-term clinical outcomes., Methods and Results: Two hundred twenty-five consecutive patients presenting with cardiac chest pain/dyspnoea, stable troponin elevation, and undergoing CMR assessment were identified retrospectively from registry database. The study cohort was prospectively followed for major adverse cardiac events (MACEs) (defined as composite of all-cause mortality and cardiovascular readmissions). The primary outcome measure was the diagnostic utility of CMR, i.e. percentage of patients for whom CMR identified the cause of stable troponin elevation. Secondary outcome measures included the incremental value of CMR and occurrence of MACE. CMR was able to identify the cause for stable troponin elevation in 160 (71%) patients. A normal CMR was identified in 17% and an inconclusive CMR in 12% of the patients. CMR changed the referral diagnosis in 59 (26%) patients. Utilizing a baseline prediction model (pre-CMR referral diagnosis), the net reclassification index was 0.11 and integrated discriminatory improvement index measured 0.33 following CMR. Over a median follow-up of 4.3 years (interquartile range 2.8-6.3), 72 (32%) patients experienced MACE., Conclusion: CMR identified a cause for stable troponin elevation in 7 of 10 cases, and a new diagnosis was evident in 1 of 4 cases. CMR improved the net reclassification of patients with stable troponin elevation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Dietary nitrate, found predominantly in green leafy vegetables and other vegetables such as radish, celery, and beetroot, has been shown to beneficially modulate inflammatory processes and immune cell function in animals and healthy individuals. The impact of increased nitrate intake on soluble inflammatory mediators in individuals with hypertension is unclear. We assessed whether the daily consumption of dietary nitrate via beetroot juice for 1-week lowered levels of circulating inflammatory markers in men and women with treated hypertension. Twenty-seven male and female participants were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effects of 1-week intake of nitrate-rich beetroot juice versus 1-week intake of nitrate-depleted beetroot juice (placebo) were investigated. Plasma concentrations of circulating soluble adhesion molecules (ICAM-1, VCAM-1, CD62E, CD62P), inflammatory cytokines (IL-1β, IL-6, IL-10, IL-12p70, TNF-α) and chemokines (IL-8, MCP-1) were measured by multiplex flow cytometric bead array in samples collected on day 7 of each intervention period. Other outcomes included alterations in nitrate metabolism assessed by measuring nitrate and nitrite concentrations in plasma, saliva, and urine. One week of beetroot juice did not alter levels of the soluble adhesion markers or cytokines assessed. A 7-fold increase in salivary nitrite, an 8-fold increase in salivary nitrate, a 3-fold increase in plasma nitrate and nitrite, and a 4-fold increase in urinary nitrate and nitrite compared to the placebo was observed ( p < 0.001 for all comparisons). Increasing dietary nitrate consumption over 7 days is not effective in reducing soluble inflammatory mediators in individuals with treated hypertension. This trial was registered at anzctr.org.au as ACTRN 12613000116729.

An up-to-date nitrate food composition database of plant-based foods is lacking. Such a resource is imperative to obtain a robust assessment of dietary nitrate intakes and facilitate more empirical evaluation of health implications. We updated and expanded our 2017 vegetable nitrate database by including data published between 2016 and 2021, and data on fruits, cereals, herbs, spices, pulses and nuts (1980 - 2021). Of the collated nitrate contents for 264 plant-based foods from 64 countries, 120 were obtained from three or more references. Despite substantial variations, leaf vegetables were the top nitrate-containing foods, followed by stem & shoot vegetables, herbs and spices, root vegetables, flower vegetables, tuber vegetables, nuts, fruit vegetables, legume/seed vegetables, fruits and cereals. Banana and strawberry contained far higher amounts of nitrate than previously recognised. In conjunction with the recent animal-based food nitrate & nitrite database, this database can now be used to evaluate dietary nitrate intake in clinical and epidemiological studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and aims: Medication usage varies according to prescribing behavior, professional recommendations, and the introduction of new drugs. Local surveillance of medication usage may be useful for understanding and comparing prescribing practices by healthcare providers, particularly in countries such as Australia that are in the process of enhancing nationwide data linkage programs. We sought to investigate the utility of electronic hospital admission data to investigate local trends in medication use, to determine similarities and differences with other Australian studies, and to identify areas for targeted interventions. Methods: We performed a retrospective longitudinal analysis using combined data from a hospital admissions administrative dataset from a large tertiary teaching hospital in Adelaide, South Australia and a hospital administrative database documenting medication usage matched for the same set of patients. All adult admissions over a 12-year period, between 1 January 2007 and 31st December 2018, were included in the study population. Medications were categorized into 21 pre-defined drug classes of interest according to the ATC code list 2021. Results: Of the 692,522 total admissions, 300,498 (43.4%) had at least one recorded medication. The overall mean number of medications for patients that were medicated increased steadily from a mean (SD) of 5.93 (4.04) in 2007 to 7.21 (4.98) in 2018. Results varied considerably between age groups, with the older groups increasing more rapidly. Increased medication usage was partly due to increased case-complexity with the mean (SD) Charlson comorbidity index increasing from 0.97 (1.66) in 2007-to-2012 to 1.17 (1.72) in 2013-to-2018 for medicated patients. Of the 21 medication classes, 15 increased ( p < 0.005), including antithrombotic agents; OR = 1.18 [1.16-1.21], proton pump inhibitors; OR = 1.14 [1.12-1.17], statins; OR = 1.12; [1.09-1.14], and renin-angiotensin system agents; OR = 1.06 [1.04-1.08], whilst 3 decreased ( p < 0.005) including anti-inflammatory drugs (OR = 0.55; 99.5% CI = 0.53-0.58), cardiac glycosides (OR = 0.81; 99.5% CI = 0.78-0.86) and opioids (OR = 0.82; 99.5% CI = 0.79-0.83). The mean number of medications for all admissions increased between 2007 and 2011 and then declined until 2018 for each age group, except for the 18-to-35-year-olds. Conclusion: Increased medication use occurred in most age groups between 2007 and 2011 before declining slightly even after accounting for increased comorbidity burden. The use of electronic hospital admission data can assist with monitoring local medication trends and the effects of initiatives to enhance the quality use of medicines in Australia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Woodman, Horwood, Kunnel, Hakendorf and Mangoni.)

Objectives: To evaluate the association between C-reactive protein (CRP) and 10-year risk of cardiovascular (CV) events using the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), based on conventional and RA-specific risk factors but not CRP, in RA patients without previous cardiovascular events., Methods: ERS-RA was calculated in 1,251 "Cardiovascular Obesity and Rheumatic Disease Study (CORDIS)" database patients [(age 60.4(9.3) years; 78% female; disease duration, 11.6(8) years; CDAI, 9(9); CRP, 6.8(12) mg/L]., Results: The mean (SD) 10-year risk of CV events was 12.9% (10). After adjusting for the use of DMARDs and biologics, CRP concentrations were significantly associated with 10-year risk of CV events (coefficient=0.005 for each 10 mg/L CRP increment; 95%CI 0.000-0.111; p = 0.047). In mediation analysis, the association between CRP and ERS-RA was not explained by disease activity., Conclusion: In a large cohort of RA patients without previous cardiovascular events, a 20 mg/L increase in CRP concentrations was associated with a 1% increase in 10-year risk of CV events. This suggests that actively targeting residual inflammatory risk beyond conventional and RA-specific risk factors might further reduce CV event rates in RA patients., Competing Interests: Declaration of Competing Interests All Authors report no conflict of interest., (Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Thirty-day mortality following coronary artery bypass grafting (CABG) is a widely accepted marker for quality of care. Although surgical mortality has declined, the utility of this measure to profile quality has not been questioned. We assessed the institutional variation in risk-standardised mortality rates (RSMR) following isolated CABG within Australia and New Zealand (ANZ)., Methods: We used an administrative dataset from all public and most private hospitals across ANZ to capture all isolated CABG procedures recorded between 2010 and 2015. The primary outcome was all-cause death occurring in-hospital or within 30-days of discharge. Hospital-specific RSMRs and 95% CI were estimated using a hierarchical generalised linear model accounting for differences in patient characteristics., Results: Overall, 60,953 patients (mean age 66.1 ± 10.1y, 18.7% female) underwent an isolated CABG across 47 hospitals. The observed early mortality rate was 1.69% (n = 1029) with 81.8% of deaths recorded in-hospital. The risk-adjustment model was developed with good discrimination (C-statistic = 0.81). Following risk-adjustment, a 3.9-fold variation was observed in RSMRs among hospitals (median:1.72%, range:0.84-3.29%). Four hospitals had RSMRs significantly higher than average, and one hospital had RSMR lower than average. When in-hospital mortality alone was considered, the median in-hospital RSMR was 1.40% with a 5.6-fold variation across institutions (range:0.57-3.19%)., Conclusions: Average mortality following isolated CABG is low across ANZ. Nevertheless, in-hospital and 30-day mortality vary among hospitals, highlighting potential disparities in care quality and the enduring usefulness of 30-day mortality as an outcome measure. Clinical and policy interventions, including participating in clinical quality registries, are needed to standardise CABG care., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Unplanned hospital readmissions (HRA), which have been used as key performance index of healthcare quality, are becoming more prevalent. They are associated with substantial financial burden to hospital systems and considerable impacts on patients' physical and mental health. Patients with frequent readmissions are not well studied., Aims: To determine the prevalence, characteristics and risk factors associated with frequent readmissions (FRA) to an internal medicine service at a tertiary public hospital., Method: A retrospective observational study was conducted at an internal medicine service in a tertiary teaching hospital between 1 January 2010 and 30 June 2016. FRA was defined as four or more readmissions within 12 months of discharge from the index admission (IA). Demographic and clinical characteristics and potential risk factors were evaluated., Results: A total of 50 515 patients was included; 1657 (3.3%) had FRA and were associated with nearly 2.5 times higher in 12-month mortality rates. They were older, had higher rates of indigenous Australians (3.2%), more disadvantaged status (index of relative socio-economic disadvantage decile of 5.3) and more comorbidities (mean Charlson comorbidity index 1.4) in comparison, to infrequent readmission group. The mean length of hospital stay during the IA was 6 days for FRA group (21.4% staying more than 7 days) with higher incidence of discharge against medical advice (2.0% higher). Intensive care unit admission rate was 6.6% for FRA group compared with 3.9% for infrequent readmission group. Multivariate analysis showed mental disease and disorders, neoplastic, alcohol/drug use and alcohol/drug-induced organic mental disorders are associated with FRA., Conclusion: The risk factors associated with FRA were older age, indigenous status, being socially disadvantaged, having higher comorbidities and discharging against medical advice. Conditions that lead to FRA were mental disorders, alcohol/drug use and alcohol/drug-induced organic mental disorders and neoplastic disorders., (© 2021 Royal Australasian College of Physicians.)

Study Question: Does maternal exposure to first trimester corticosteroids in IVF/ICSI treatment result in an increased risk of congenital anomalies?, Summary Answer: Children born with the aid of IVF/ICSI whose mothers were treated with adjuvant corticosteroids during the first trimester had an increased risk of cryptorchidism, hypospadias and talipes., What Is Known Already: Maternal exposure to corticosteroids may increase the risk of congenital anomalies such as cleft palate and neural tube defects. However, the existing studies have conflicting outcomes, are underpowered, and do not study a population undergoing IVF/ICSI, a group known to be at increased risk of abnormalities., Study Design, Size, Duration: This retrospective cohort analysis covering Monash IVF fertility clinics in Melbourne, Australia assessed the outcomes of 12 426 live births from both fresh and frozen embryo transfers between 2010 and 2016., Participants/materials, Setting, Methods: There were 618 live births included in our study group of mothers exposed to corticosteroids (oral prednisolone or dexamethasone) during their IVF/ICSI treatment, with the remainder of births not exposed to steroids (control, n = 11 808). The primary outcome measured was the presence of congenital anomalies and secondary outcomes were birth weight and gestation length. Multivariate binary logistic regression was used to assess the independent effects of corticosteroid exposure and the freezing of embryos, with adjustment for maternal age at oocyte retrieval, smoking status, number of cycles taken, BMI, etiology of the infertility and the use of ICSI. Results are presented as incidence rate ratios (IRRs) with 95% CIs., Main Results and the Role of Chance: Amongst 12 426 live births, and 597 birth defects, multivariate logistic regression demonstrated there was an increased incidence in talipes equinovarus (1.33% vs 0.32%, adjusted IRR = 4.30, 95% CI = 1.93, 9.58; P < 0.001), hypospadias (0.66% vs 0.18%, adjusted IRR = 5.90, 95% CI = 2.09, 16.69; P = 0.001) and cryptorchidism (0.83% vs 0.19%, adjusted IRR = 5.53, 95% CI = 1.91, 15.42; P = 0.001) in the offspring of mothers exposed to corticosteroids compared to those who were unexposed. The incidence of neither neural tube defects nor cleft palate were significantly increased in babies exposed to corticosteroids. The sex ratio of infants exposed to corticosteroids during a fresh embryo transfer cycle significantly favored males but reverted to the normal sex ratio in infants conceived in frozen embryo transfer cycles., Limitations, Reasons for Caution: This was a retrospective observational cohort study using administrative datasets with the potential for measurement error and unobserved confounding. Missing outcome data were obtained from patients using self-report leading to possible ascertainment bias. Given the rare incidence of some of the anomalies assessed, the study was underpowered to identify differences in abnormality rates for some specific anomalies., Wider Implications of the Findings: The findings of this study, the largest of its kind, suggest that caution should be heeded when prescribing corticosteroids to women undergoing IVF/ICSI, given that this study has now identified three previously unassociated serious neonatal complications (talipes, hypospadias and cryptorchidism), plus a potential alteration in sex ratio. Physicians should be careful in using corticosteroids in the critical first trimester and should counsel patients regarding the potential risks of this treatment., Study Funding/competing Interest(s): There was no funding sought or obtained for this study. K.T., V.T., B.V. and D.Z.-F. are employees or contractors to Monash IVF and hold a minority stock position in Monash IVF. R.J.W. reports no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mediterranean populations enjoy the health benefits of a Mediterranean diet (MedDiet), but is it feasible to implement such a pattern beyond the Mediterranean region? The MedLey trial, a 6-month MedDiet intervention vs habitual diet in older Australians, demonstrated that the participants could maintain high adherence to a MedDiet for 6 months. The MedDiet resulted in improved systolic blood pressure (BP), endothelial dilatation, oxidative stress, and plasma triglycerides in comparison with the habitual diet. We sought to determine if 12 months after finishing the MedLey study, the participants maintained their adherence to the MedDiet principles and whether the reduction in the cardiovascular disease (CVD) risk factors that were seen in the trial were sustained. Participants completed a food frequency questionnaire, and a 15-point MedDiet adherence score (MDAS; greater score = greater adherence) was calculated. Home BP was measured over 6 days, BMI was assessed, and fasting plasma triglycerides were measured. The data were analysed using intention-to-treat linear mixed effects models with a group × time interaction term, comparing data at baseline, 2, 4, and 18 months (12 months post-trial). At 18 months (12 months after finishing the MedLey study), the MedDiet group had a MDAS of 7.9 ± 0.3, compared to 9.6 ± 0.2 at 4 months (p < 0.0001), and 6.7 ± 0.2 (p < 0.0001), at baseline. The MDAS in the HabDiet group remained unchanged over the 18-month period (18 months 6.9 ± 0.3, 4 months 6.9 ± 0.2, baseline 6.7 ± 0.2). In the MedDiet group, the consumption of olive oil, legumes, fish, and vegetables remained higher (p < 0.01, compared with baseline) and discretionary food consumption remained lower (p = 0.02) at 18 months. These data show that some MedDiet principles could be adhered to for 12 months after finishing the MedLey trial. However, improvements in cardiometabolic health markers, including BP and plasma triglycerides, were not sustained. The results indicate that further dietary support for behaviour change may be beneficial to maintaining high adherence and metabolic benefits of the MedDiet.

Background and Aim: The rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM)., Methods: Barcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence-free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding., Results: Two hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty-two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P  < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years ( P  = 0.019), 2.45 years ( P  < 0.001), and 1.64 years ( P  < 0.001) for OS, LTC, and RFS, respectively. Three-year LTC after PA was suboptimal (65%)., Conclusion: Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined., Methods: Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location., Results: Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (β = 3.85% per 10% increase in a postcode's migrant population; P < 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P < 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance., Conclusion: Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy., (© 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: Studies examining the association between obesity and mortality in cardiac arrest patients have been conflicting which might either be due to residual confounding, or a reliance on estimating the conditional effects rather than the marginal (causal) effects of obesity. We estimated the conditional and causal effects of obesity on mortality in cardiac arrest patients using the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD)., Materials and Methods: This retrospective registry-based cohort study from ICUs of Australia and New Zealand included all ICU patients admitted with cardiac arrest between 2010 and 2020 with height and weight data recorded. The conditional and marginal effects of obesity on mortality was estimated using multivariate binary logistic regression and Targeted Maximum Likelihood Estimation (TMLE) respectively. The primary outcome was in-hospital mortality., Results: A total 13,970 patients had complete data and were available for analysis. In multivariate binary logistic regression, there was no difference in the odds of in-hospital mortality for the obese versus non-obese groups; adjusted OR = 0.95, 95% CI = 0.87-1.03; p 0.25. Results were similar using TMLE (Marginal OR= 0.97; 95% CI = 0.91-1.02, p = 0.62)., Conclusion: After adjustment, there was no association between obesity and outcomes in cardiac arrest patients admitted to ICU., Competing Interests: Declaration of Competing Interest None., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: Admission to hospital introduces risks for people with Parkinson's disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual's symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome., Objective: To determine the occurrence and identify factors that contribute to Parkinson's medication errors in Australian hospitals., Methods: A retrospective discharge diagnosis code search identified all admissions for people with Parkinson's disease to three tertiary metropolitan hospitals in South Australia, Australia over a 3-year period. Of the 405 case notes reviewed 351 admissions met our inclusion criteria., Results: Medication prescribing (30.5%) and administration (85%) errors during admission were extremely common, with the most frequent errors related to administration of levodopa preparations (83%). A higher levodopa equivalent dosage, patients with a modified swallowing status or nil by mouth order during admission, and patients who did not have a pharmacist led medication history within 24 hours of admission had significantly higher rates of medication errors., Conclusions: This study identified 3 major independent factors that increased the risk of errors during medication management for people with Parkinson's disease during hospitalization. Thus, targeting these areas for preventative interventions have the greatest chance of producing a clinically meaningful impact on the number of hospital medication errors occurring in the Parkinson's population., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine the placebo response rate in PsA randomized clinical trials (RCTs), its contributing factors and impact on the effect size of active treatments., Methods: We searched multiple databases, from inception to 20 December 2020, for placebo-controlled RCTs in PsA. We used a random-effects meta-analysis to pool the response rates for the ACR20 criteria in the placebo arm, determined the risk difference for treatment vs placebo, and used meta-regression to determine the factors associated with placebo response rates. The risk of bias was assessed in duplicate. The study protocol was registered with PROSPERO: CRD42021226000., Results: We included 42 RCTs (5050 patients receiving placebo) published between 2000 and 2020. The risk of bias was low in 28 trials, high in four, and with some concerns in 10. The pooled placebo response rate was 20.3% (95% CI: 18.6%, 22.1%; predicted intervals, 11.7-29.0%), with significant between-trial heterogeneity (I2 = 56.8%, P < 0.005). The pooled risk difference for treatment vs placebo was 27% (95% CI: 24%, 31%). In the multivariable meta-regression, there was a 15% (95% CI: 2.9%, 29.8%) increase in the odds of achieving the placebo response for each 5-year increment in publication year (P = 0.016). In addition, the active treatment risk difference decreased for every 5-year increment in publication year (β = -0.053, 95% CI: -0.099, -0.007; P = 0.024) but was not associated with the placebo response., Conclusion: Despite increasing over time, the placebo response for ACR20 in PsA RCTs was not associated with the active treatment effect size., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: The comparative utility of physiological reserve measures in predicting important clinical outcomes following liver transplantation (LT) requires further study. The aim of this work was therefore to compare the utility of physiological reserve measures in predicting early adverse clinical outcomes post-LT., Methods: A single-center, retrospective cohort study of LT patients consecutively recruited between 1 January 2015, and 31 August 2020. Outcomes measured were sepsis and death within 12 months of LT, hospital length of stay (LOS), and intensive care LOS. Physiological reserve measures were handgrip strength, mid-arm muscle circumference, and cardiopulmonary exercise testing (CPET) measures. Analysis was performed using univariate and multivariate logistic regression for sepsis and death, and univariate and multivariate Cox regression for hospital and intensive care LOS., Results: Data were obtained for 109 subjects. Patients were predominantly (64%) male with a median (interquartile range [IQR]) age of 57 (49-63) and median (IQR) Model for End-Stage Liver Disease score of 16 (11-21). In multivariate analysis, the odds of sepsis were lower in patients in the highest versus lowest tertile (odds ratio = 0.004; 95% confidence interval [CI] 0.00-0.13; P  = 0.002). Hospital LOS was linearly associated with handgrip strength (hazard ratio [HR] = 1.03; 95% CI 1.00-1.06; P  = 0.03) in multivariate analysis. Intensive care LOS was associated with peak VO 2 (HR 1.83; 95% CI 1.06-3.16; P  = 0.03) and V E /VCO 2 slope (HR 0.71; 95% CI 0.58-0.88; P  = 0.002) in multivariate analysis., Conclusion: Handgrip strength and CPET both identify candidates at high risk of adverse outcomes after LT., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Scope: Nitrate and nitrite are approved food additives in some animal-based food products. However, nitrate and nitrite in foods are strictly regulated due to health concerns over methaemoglobinaemia and the potential formation of carcinogenic nitrosamines. In contrast, plants (like leafy vegetables) naturally accumulate nitrate ions; a growing body of research reveals beneficial metabolic effects of nitrate via its endogenous conversion to nitric oxide. To refine the association of dietary nitrate and nitrite intake with health outcomes, reliable measures of nitrate and nitrite intake from dietary food records are required. While a vegetable nitrate content database has been developed, there is a need for a comprehensive up-to-date nitrate and nitrite content database of animal-based foods., Methods and Results: A systematic literature search (1980-September 2020) on the nitrate and nitrite content of animal-based foods is carried out. Nitrate and nitrite concentration data and other relevant information are extracted and compiled into a database. The database contains 1921 entries for nitrate and 2077 for nitrite, extracted from 193 publications. The highest median nitrate content is observed in chorizo (median [IQR]; 101.61 [60.05-105.93] mg kg -1 ). Canned fish products have the highest median nitrite level (median [IQR]; 20.32 [6.16-30.16] mg kg -1 ). By subgroup, the median nitrate value in industrial processed meat products (e.g., uncured burger, patties and sausages), whole milk powder and in particular red meat are higher than cured meat products. Processed meat products from high-income regions have lower median nitrate and nitrite content than those of middle-income regions., Conclusion: This database can now be used to investigate the associations between nitrate and nitrite dietary intake and health outcomes in clinical trials and observational studies., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Study Objectives: The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat)., Methods: This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed., Results: The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04-0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement., Conclusions: This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required., Clinical Trial: This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Severe thrombocytopenia in cirrhosis can preclude invasive procedures. Platelet transfusion is recommended if platelet count pre-procedure is potential alternative to platelet transfusion is thrombopoietin-receptor (TPO) agonists., Aim: Evaluate TPO-agonist efficacy and safety in cirrhotic patients with severe thrombocytopenia undergoing invasive procedures., Methods: Randomized control trials (RCT) from electronic reference databases were searched from inception till December 2019. PRISMA guidelines were followed. Primary outcome was platelet transfusion avoidance. Secondary outcomes were weighted mean difference (WMD) in platelet count from baseline to pre-procedure and rates of major adverse events (AE). Pooled Odds Ratio (OR) were estimated using a random-effects model., Results: Six RCTs with 1,229 patients were included. All studies had low risk of bias. Compared with placebo, those treated with TPO-agonists had a pooled OR of 0.12(0.08-0.17), P<0.01 for platelet transfusion avoidance, and WMD in platelet count (x10 3 /µL) of 35.6(28.6-42.7), P<0.01. Major AE did not differ between groups [Pooled OR: 0.87(0.47-1.62), P=0.66]., Conclusion: Compared to placebo, TPO-agonists used in cirrhotic patients with severe thrombocytopenia prior to elective invasive procedures had 88% reduced odds of requiring peri-procedural platelet transfusion and increased platelet count pre-procedure, with no difference in AE rates., Competing Interests: Conflict of Interest The authors of the manuscript titled, “Pre-procedural use of thrombopoietin-receptor agonists in cirrhosis and severe thrombocytopenia: A systematic review and meta-analyze” have no conflict of interest to declare. All authors received no support in the form of grants, equipment or drugs. Dr Peter D Rose; Dr Minnie Au; Professor R Woodman; Dr Derrick Tee; Dr Mohamad A Chinnaratha., (Copyright © 2021. Published by Elsevier Ltd.)

Background: SARS-CoV-2 poses a considerable threat to those living in residential aged care facilities (RACF). RACF COVID-19 outbreaks have been characterised by the rapid spread of infection and high rates of severe disease and associated mortality. Despite a growing body of evidence supporting airborne transmission of SARS-CoV-2, current infection control measures in RACF including hand hygiene, social distancing, and sterilisation of surfaces, focus on contact and droplet transmission. Germicidal ultraviolet (GUV) light has been used widely to prevent airborne pathogen transmission. Our aim is to investigate the efficacy of GUV technology in reducing the risk of SARS-CoV-2 infection in RACF., Methods: A multicentre, two-arm double-crossover, randomised controlled trial will be conducted to determine the efficacy of GUV devices to reduce respiratory viral transmission in RACF, as an adjunct to existing infection control measures. The study will be conducted in partnership with three aged care providers in metropolitan and regional South Australia. RACF will be separated into paired within-site zones, then randomised to intervention order (GUV or control). The initial 6-week period will be followed by a 2-week washout before crossover to the second 6-week period. After accounting for estimated within-zone and within-facility correlations of infection, and baseline infection rates (10 per 100 person-days), a sample size of n = 8 zones (n = 40 residents/zone) will provide 89% power to detect a 50% reduction in symptomatic infection rate. The primary outcome will be the incidence rate ratio of combined symptomatic respiratory infections for intervention versus control. Secondary outcomes include incidence rates of hospitalisation for complications associated with respiratory infection; respiratory virus detection in facility air and fomite samples; rates of laboratory confirmed respiratory illnesses and genomic characteristics., Discussion: Measures that can be deployed rapidly into RACF, that avoid the requirement for changes in resident and staff behaviour, and that are effective in reducing the risk of airborne SARS-CoV-2 transmission, would provide considerable benefit in safeguarding a highly vulnerable population. In addition, such measures might substantially reduce rates of other respiratory viruses, which contribute considerably to resident morbidity and mortality. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000567820 (registered on 14th May, 2021)., (© 2021. The Author(s).)

Background: Little is known about the utilisation and safety of catheter ablation of atrial fibrillation (AF) among public and private sector hospitals., Aims: To examine the uptake of AF ablations and compare procedural safety between the sectors., Method: Hospitalisation data from all public and private hospitals in four large Australian states (NSW, QLD, VIC and WA) were used to identify patients undergoing AF ablation from 2012 to 17. The primary endpoint was any procedure-related complications up to 30-days post-discharge. Logistic regression was used to evaluate the association between treatment at a public hospital and risk of complications adjusting for covariates., Results: Private hospitals performed most of the 21,654 AF ablations identified (n = 16,992, 78.5 %), on patients who were older (63.5 vs. 59.9y) but had lower rates of heart failure (7.9 % vs. 10.4 %), diabetes (10.2 % vs. 14.1 %), and chronic kidney diseases (2.4 % vs. 5.2 %) (all p < 0.001) than those treated in public hospitals. When compared with private hospitals, public hospitals had a higher crude rate of complications (7.25 % vs. 4.70 %, p < 0.001). This difference remained significant after adjustment (OR 1.74 [95 % CI 1.54-2.04]) and it occurred with both in-hospital (OR 1.83 [1.57-2.14]) and post-discharge (OR 1.39 [1.06-1.83]) complications, with certain complications including acute kidney injury (OR 5.31 [3.02-9.36]), cardiac surgery (OR 5.18 [2.19-12.27]), and pericardial effusion (OR 2.18 [1.50-3.16])., Conclusions: Private hospitals performed most of AF ablations in Australia with a lower rate of complications when compared with public hospitals. Further investigations are needed to identify the precise mechanisms of this observed difference., (© 2021. The Author(s).)

Background: Following stroke, changes in neuronal connectivity in tissue surrounding the infarct play an important role in both spontaneous recovery of neurological function and in treatment-induced improvements in function. Microglia and astrocytes influence this process through direct interactions with the neurons and as major determinants of the local tissue environment. Subpopulations of peri-infarct glia proliferate early after stroke providing a possible target to modify recovery. Treatment with cell cycle inhibitors can reduce infarct volume and improve functional recovery. However, it is not known whether these inhibitors can influence neurological function or alter the responses of peri-infarct glia without reducing infarction. The present study aimed to address these issues by testing the effects of the cell cycle inhibitor, olomoucine, on recovery and peri-infarct changes following photothrombotic stroke., Methods: Stroke was induced by photothrombosis in the forelimb sensorimotor cortex in Sprague-Dawley rats. Olomoucine was administered at 1 h and 24 h after stroke induction. Forelimb function was monitored up to 29 days. The effects of olomoucine on glial cell responses in peri-infarct tissue were evaluated using immunohistochemistry and Western blotting., Results: Olomoucine treatment did not significantly affect maximal infarct volume. Recovery of the affected forelimb on a placing test was impaired in olomoucine-treated rats, whereas recovery in a skilled reaching test was substantially improved. Olomoucine treatment produced small changes in aspects of Iba1 immunolabelling and in the number of CD68-positive cells in cerebral cortex but did not selectively modify responses in peri-infarct tissue. The content of the astrocytic protein, vimentin, was reduced by 30% in the region of the lesion in olomoucine-treated rats., Conclusions: Olomoucine treatment modified functional recovery in the absence of significant changes in infarct volume. The effects on recovery were markedly test dependent, adding to evidence that skilled tasks requiring specific training and general measures of motor function can be differentially modified by some interventions. The altered recovery was not associated with specific changes in key responses of peri-infarct microglia, even though these cells were considered a likely target for early olomoucine treatment. Changes detected in peri-infarct reactive astrogliosis could contribute to the altered patterns of functional recovery., (© 2021. The Author(s).)