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Background: Thiopurine co‐therapy with anti‐tumour necrosis factor‐alpha (anti‐TNFα) agents is associated with higher anti‐TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). Aims: We aimed to evaluate the association between 6‐thioguanine nucleotide (6‐TGN) and anti‐TNFα levels and the optimal 6‐TGN threshold level associated with higher anti‐TNFα levels in combination therapy. Methods: We performed a retrospective cross‐sectional multicentre study of patients with IBD on combination anti‐TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti‐TNFα levels. Receiver operator characteristic curves were used to define the optimal 6‐TGN cut‐off levels associated with therapeutic anti‐TNFα levels. Results: The study included 743 paired 6‐TGN and anti‐TNFα levels (640 infliximab and 103 adalimumab). 6‐TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6‐TGN cut‐off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6‐TGN cut‐off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. Conclusion: 6‐TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6‐TGN levels in the lower end of the therapeutic range (230–260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing. [ABSTRACT FROM AUTHOR]

The article focuses on the Australian essential oil industry, highlighting key oils such as Tea Tree, Eucalyptus, Sandalwood, Lemon Myrtle, and Lavender, along with ongoing research initiatives. Topics include the production statistics of various essential oils, advancements in breeding programs, genomic studies, chiral assignments, and the discovery of novel compounds like acylphloroglucinols in Tea Tree seedlings, suggesting potential for new commercial opportunities.

Background. Rheumatoid arthritis (RA) is an inflammatory condition that causes joint damage and is associated with pain. The biological disease-modifying antirheumatic drugs (bDMARDs) for RA are linked to additional therapeutic benefits as they suppress the inflammatory process, which in turn prevents joint erosion and reduces pain. Thus, the use of bDMARDs has the potential to reduce the need for other analgesic and anti-inflammatory therapies for RA. The aim of this study was to examine the analgesic and anti-inflammatory use around the initiation of bDMARDs. Methods. A cohort study was conducted using a 10% random sample of the population dispensing medicines under the Australian Pharmaceutical Benefits Scheme. People who initiated the first bDMARD for RA between 2014 and 2018 were included. The proportion who received any analgesic or anti-inflammatory, including nonsteroidal anti-inflammatory drugs, opioids, or glucocorticoids, in the twelve months prior to and post-bDMARD initiation was determined and compared using regression models. Results. There were 18,360 persons in the cohort, with a mean age of 55 years, and 69% were women. The use of any analgesic or anti-inflammatory in both tumor necrosis factor inhibitor (TNFi) and non-TNF initiators increased prior to initiation of bDMARD–from 43% to 52% in TNFi and from 52% to 63% in non-TNF initiators. In both groups, overall use decreased significantly post initiation to 37% and 42% in TNFi and non-TNF initiators, respectively (p < 0.0001). bDMARD initiation was associated with lower use of glucocorticoid therapy, but there was no decreasing effect on opioid use. Conclusion. While the use of any analgesic or anti-inflammatories decreased post-initiation of bDMARDs for RA, more than one-third of people were dispensed analgesic or anti-inflammatory agents twelve months post initiation. Ongoing review of the need for analgesic and glucocorticoids appears warranted, with assessment of nonpharmacological approaches to support pain management. [ABSTRACT FROM AUTHOR]

Background: Severe COVID‐19 causes acute inflammation, which is complicated by venous thromboembolism events (VTE). However, it is unclear if VTE risk has evolved over time since the COVID‐19 outbreak. Aims: To determine markers of thrombo‐inflammation and rates of symptomatic VTE in patients hospitalised for COVID‐19 in a metropolitan hospital in Sydney, Australia. Methods: A retrospective, single‐centre, cohort study was performed by reviewing electronic medical records of consecutive patients admitted to Royal Prince Alfred Hospital between March 2020 and September 2021. This period included three waves of COVID‐19 outbreaks in Australia with the ancestral, alpha and delta variants. Standard coagulation assays and inflammatory markers were recorded over 4 weeks. Results: A total of 205 patients were consecutively admitted during the study period. Activated partial thromboplastin time, neutrophil count and C‐reactive protein (CRP) were significantly increased in patients hospitalised in the intensive care unit (ICU) compared with non‐ICU patients. The use of anti‐inflammatory medication increased in 2021 compared with 2020. The mortality rate was 7.3% in our cohort. Ninety‐four per cent of patients received anticoagulation with 6.3% of patients developing VTE. Conclusion: We observed lower rates of VTE compared to the internationally reported rate for the same period. We conclude that in the setting of controlled hospital admission rate and standard anticoagulation guidelines, COVID‐19 resulted in similar thrombo‐inflammatory response and VTE rates over the first 1.5 years of the pandemic. [ABSTRACT FROM AUTHOR]

Objectives: Acute kidney injury (AKI) is a well‐known but poorly documented adverse effect of non‐steroidal anti‐inflammatory drugs (NSAIDs) in cats. We aimed to describe instances of NSAID‐associated AKI in cats and survey Australian veterinarians on NSAID use in acute settings. Methods: Medical records of cats that developed an AKI subsequent to the administration of meloxicam were obtained by searching the databases of seven practices in Queensland, as well as by contemporaneously contacting select veterinary colleagues of the authors in both general and specialist small animal practice. An online questionnaire was created for the survey, and the URL distributed to Australian practitioners. Results: A total of 18 cases were retrieved, all of which received injectable meloxicam. The indication(s) for its use and the dosage prescribed were within the manufacturer's recommendations for Australian veterinarians. The majority of cases (13/18 cats) received the label dose of 0.3 mg/kg subcutaneously (SC) on the day of the procedure. In 12/18 cats, the injection was given in association with general anaesthesia or sedation. Fourteen cats survived to hospital discharge. Of 187 survey respondees, 89% routinely administered NSAIDs for surgery‐related analgesia, with 98% prescribing meloxicam and 84% of these giving it SC. Ninety percent of respondees routinely administered NSAIDs for non‐surgical‐related analgesia, with 99% prescribing meloxicam and 35% of those giving it SC. Conclusions and Relevance: We strongly recommend that practitioners avoid prescribing meloxicam SC in cats. This recommendation is emphatic in situations where concurrent dehydration and/or hypotension are possible. [ABSTRACT FROM AUTHOR]

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-to2018 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 reninangiotensin 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. [ABSTRACT FROM AUTHOR]

Plants have been a vital source of natural antioxidants since ancient times. Plants growing under various abiotic stress conditions often produce more defensive secondary metabolites such as phenolics, flavonoids, and terpenoids during adaptation to the environment. Many of these secondary metabolites are known to possess antioxidant and anti-inflammatory properties. This study tested seven plants sourced from the mountaintop areas (above 1000 m elevation) of Mount Lewis National Park (falls under the Wet Tropics of Queensland), Australia, for their antioxidant and anti-inflammatory activities. Of the seven studied plants, hydroethanolic extracts of six plants (Leptospermum wooroonooran, Ceratopetalum hylandii, Linospadix apetiolatus, Garcinia brassii, Litsea granitica, and Polyscias willmottii) showed high 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging activity in a dose-dependent (25–1000 μg/mL) manner. At the highest concentration of 1 mg/mL, the DPPH free radical scavenged percentage varied between 75.4% and 92.3%. Only the species Alyxia orophila was inactive in the DPPH free radical scavenging assay. Pseudo-IC50 values of the extracts' ferric reducing antioxidant power (FRAP) based on dose-response curves showed a significant positive correlation with total phenolic content. Five out of the seven plants, namely G. brassii, C. hylandii, L. apetiolatus, L. wooroonooran, and A. orophila, showed inhibitory effects on the secretion of proinflammatory cytokines, tumour necrosis factor (TNF), and interleukins (IL)-23 in a lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) assay. The results of this study demonstrate the value of tropical mountaintop plants in the biodiscovery of antioxidant and anti-inflammatory lead compounds. [ABSTRACT FROM AUTHOR]

We report two cases of middle‐aged men who presented with clinical features that satisfied the diagnostic criteria for multisystem inflammatory syndrome in adults (MIS‐A). Both patients were treated for toxic shock syndrome and MIS‐A and have recovered. The purpose of this article is to communicate our experience and challenges of assessing and treating this condition and to raise awareness of the condition. [ABSTRACT FROM AUTHOR]

Background: Studies have described general practitioner (GP) management of plantar heel pain from some countries; however, there is limited information from Australian general practice. Objectives: To describe patient and GP characteristics, and management actions for plantar heel pain in Australian general practice. Design: Secondary analysis of data from the Bettering the Evaluation and Care of Health (BEACH) dataset. Methods: Data were summarised using descriptive analysis and robust 95% confidence intervals (CIs) were calculated around point estimates. Multivariate logistic regression identified predictors of plantar heel pain management. Results: From 1,568,100 encounters between April 2000 and March 2016, plantar heel pain was managed at 3007 encounters. GPs manage plantar heel pain approximately once every 500 encounters, which extrapolates to 271,100 encounters in 2015–2016. Patient factors independently associated with plantar heel pain encounters included female sex (OR 1.27, 95% CI 1.17–1.34 cf. males), being aged 45–64 (OR 3.44, 95% CI 2.94–4.01 cf. aged 75+) and patients from a non‐English speaking background (OR 1.22, 95% CI 1.07–1.39). Plantar heel pain was frequently managed using medication (45.1 per 100), with non‐steroidal anti‐inflammatory drugs the most common (22.8 per 100). GPs also commonly provided counselling/advice/education (32.4 per 100), and referrals for diagnostic imaging (19.1 per 100) and to podiatrists (12.0 per 100). Conclusions: Plantar heel pain is a frequently managed foot condition in Australian general practice. GPs use medication, counselling and education, diagnostic imaging and referral to podiatrists for management. Further research is required to understand the drivers of these management actions and whether they are effective. [ABSTRACT FROM AUTHOR]

Contact lenses are widely prescribed in clinical practice with multiple applications and advantages. However, contact lenses can be associated with various complications which range from innocuous to severe. Clinicians thus not only need to possess the ability to prescribe the most appropriate contact lenses for each individual patient but also be able to recognise and manage any associated complications. This review examines the existing literature on the management of corneal infiltrative events associated with soft contact lenses, including microbial keratitis, particularly in the context of practising in Australia. The definitions and diagnosis of corneal infiltrative events, as well as the current understanding of their aetiologies, will be explored. The various aspects of a successful management will be discussed, including the applications of therapeutic agents such as antimicrobial and anti-inflammatory agents, the role of microbiological investigations, and strategies to improve long-term prognosis. The currently available evidence supporting management options will be presented, highlighting the relative abundance of high-level evidence on management protocols, antimicrobial selection and treatment duration for microbial keratitis; and the relative paucity of studies and trials for sterile corneal infiltrative events, despite this condition being much more commonly encountered in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: This cost-analysis study explored Pharmaceutical Benefits Scheme (PBS) data to determine the financial patient contribution (PC) towards dispensed medications prescribed by dentists and temporal trends in cost contributions. Methods: For this study we used the PBS online dataset and only included concessional data in the analysis. Data on dental medications dispensed under the PBS from 2006 to 2018 were accessed. For all medicines aggregated to different pharmacological categories (antibiotics, analgesics and opiates, anti-inflammatories, antifungals, benzodiazepines, anticonvulsants and anti-emetics, and emergency medications), a temporal trend was generated using annual PC data. Cumulative patient and mean annual PC data were also generated in a similar manner. Results: Cumulative PC over the study period for dental PBS prescriptions was A$28 783 361 (A$5.55 per dispensing). The mean annual PC for dental PBS was A$2 214 105 (for the entire concessional population from 2006 to 2018), with a statistically significant and strong correlation between year and PC (Dental PBS, A$59 756 per year; r = 0.98: P < 0.0001). Antibiotics represented the highest proportion of PC (87.8%), whereas the lowest proportion of PC was for emergency medications (e.g. adrenaline, atropine, glucagon, naloxone), which amounted to 0.003%. Conclusions: This study highlights the increasing contributions made by patients towards antibiotic prescriptions. What is known about the topic?: Australian dentists can independently prescribe subsidised medications as per a set scope for general and specialist dentists, regulated under the PBS with requisite adherence to specific legal requirements. What does this paper add?: This is the first study highlighting the increased level of patient financial contributions towards dental medicines, according to different pharmacological categories, dispensed by pharmacists in Australia. What are the implications for practitioners?: This study creates a base for future research assessing the appropriateness of the PBS subsidy and the PBS Safety Net threshold, possibly reassessing the out-of-pocket pricing on brand substitution and appropriately reassessing the current dental PBS schedule. [ABSTRACT FROM AUTHOR]

8 Robson, M, Chew D, Aalast Van S. Intrinsic acute renal failure (ARF) associated with non-steroidal anti-inflammatory drug (NSAID) use in juvenile cats undergoing routine desexing- 16 cases 1998-2005. Pain behaviors before and after treatment of oral disease in cats using video assessment: a prospective, blinded, randomized clinical trial. We are writing on behalf of our respective organisations with regards to the paper " I Acute kidney injury in 18 cats after subcutaneous meloxicam and an update on non-steroidal anti-inflammatory drug usage in feline patients in Australia i ", published in the AVJ 2023 Mar;101 (3):90-98. [Extracted from the article]

Introduction: Chronic inflammation plays a key role in knee osteoarthritis pathophysiology and increases risk of comorbidities, yet most interventions do not typically target inflammation. Our study will investigate if an anti-inflammatory dietary programme is superior to a standard care low-fat dietary programme for improving knee pain, function and quality-of-life in people with knee osteoarthritis., Methods and Analysis: The eFEct of an Anti-inflammatory diet for knee oSTeoarthritis study is a parallel-group, assessor-blinded, superiority randomised controlled trial. Following baseline assessment, 144 participants aged 45-85 years with symptomatic knee osteoarthritis will be randomly allocated to one of two treatment groups (1:1 ratio). Participants randomised to the anti-inflammatory dietary programme will receive six dietary consultations over 12 weeks (two in-person and four phone/videoconference) and additional educational and behaviour change resources. The consultations and resources emphasise nutrient-dense minimally processed anti-inflammatory foods and discourage proinflammatory processed foods. Participants randomised to the standard care low-fat dietary programme will receive three dietary consultations over 12 weeks (two in-person and one phone/videoconference) consisting of healthy eating advice and education based on the Australian Dietary Guidelines, reflecting usual care in Australia. Adherence will be assessed with 3-day food diaries. Outcomes are assessed at 12 weeks and 6 months. The primary outcome will be change from baseline to 12 weeks in the mean score on four Knee injury and Osteoarthritis Outcome Score (KOOS 4 ) subscales: knee pain, symptoms, function in daily activities and knee-related quality of life. Secondary outcomes include change in individual KOOS subscale scores, patient-perceived improvement, health-related quality of life, body mass and composition using dual-energy X-ray absorptiometry, inflammatory (high-sensitivity C reactive protein, interleukins, tumour necrosis factor-α) and metabolic blood biomarkers (glucose, glycated haemoglobin (HbA1c), insulin, liver function, lipids), lower-limb function and physical activity., Ethics and Dissemination: The study has received ethics approval from La Trobe University Human Ethics Committee. Results will be presented in peer-reviewed journals and at international conferences., Trial Registration Number: ACTRN12622000440729., Competing Interests: Competing interests: PB is the founder of Defeat Diabetes and author of 'A Fat Lot of Good'. PB contributed to study design but has no role in study execution, data management, analysis or the decision to publish. The NHMRC has no role in study design and will not have any role in its execution, data management, analysis and interpretation or on the decision to submit the results for publication. JLK is an editor of the British Journal of Sports Medicine (British Medical Journal Group). AGC is an associate editor of British Journal of Sports Medicine (British Medical Journal Group). All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Anti-inflammatory bioassay-guided compound isolation from the exocarp of the Australian rainforest tree Endiandra insignis (family Lauraceae) has led to the discovery and structural elucidation of unusual α, β-unsaturated twenty-four carbon fatty acids and their positional isomers, insignoic acids A - E (1a - 5c). The stereochemistry and position of the double bond within the aliphatic chain were independently determined via NMR spectroscopy and Ozone-Induced Dissociation (OzID) Mass Spectrometry, respectively. Compounds (1a - 5c) displayed good to moderate anti-inflammatory activity in the range of 8-84 μM. The low therapeutic index observed when assessing the cell viability in the RAW macrophage cell lines, prompted us to investigate the anticancer potential of these unusual fatty acids. The anti-cancer activity was assessed in A-431 carinoma cell lines and MM649 melanoma cell lines. Insignoic acid C (3a-f) exhibited the highest level of potency with an IC 50 value of 5-7 μM against both the cell lines. The insignoic acids are the first of their kind known for incorporating an alpha-beta unsaturated system flanked next to a keto group with an additional level of oxygenation at C-6 in a 24‑carbon fatty acid backbone., Competing Interests: Declaration of competing interest 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. Published by Elsevier B.V.)

Rationale: Whether biomarkers can identify subgroups of patients with septic shock with differential treatment responses to hydrocortisone is unknown.Objectives: To determine if there is heterogeneity in effect for hydrocortisone on mortality, shock resolution, and other clinical outcomes based on baseline cortisol, aldosterone, and ascorbic acid concentrations.Methods: From May 2014 to April 2017, we obtained serum samples from 529 patients with septic shock from 22 ICUs in Australia and New Zealand.Measurements and Main Results: There were no significant interactions between the association with 90-day mortality and treatment with either hydrocortisone or placebo for total cortisol (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.16 vs. OR, 1.07; 95% CI, 1.00-1.13; P = 0.70), free cortisol (OR, 1.20; 95% CI, 1.04-1.38 vs. OR, 1.16; 95% CI, 1.02-1.32; P = 0.75), aldosterone (OR, 1.01; 95% CI, 0.97-1.05 vs. OR, 1.01; 95% CI, 0.98-1.04; P = 0.99), or ascorbic acid (OR, 1.11; 95% CI, 0.89-1.39 vs. OR, 1.05; 95% CI, 0.91-1.22; P = 0.70), respectively. Similar results were observed for the association with shock resolution. Elevated free cortisol was significantly associated with 90-day mortality (OR, 1.13; 95% CI, 1.00-1.27; P = 0.04), but total cortisol, aldosterone, and ascorbic acid were not.Conclusions: In patients with septic shock, there was no heterogeneity in effect of adjunctive hydrocortisone on mortality, shock resolution, or other clinical outcomes based on cortisol, aldosterone, and ascorbic acid concentrations. Plasma aldosterone and ascorbic acid concentrations are not associated with outcome. [ABSTRACT FROM AUTHOR]

Importance The epidemiology of episcleritis and scleritis in Australia is largely unknown. Background: To determine the incidence, prevalence and clinical characteristics of episcleritis and scleritis in Melbourne. Design Retrospective longitudinal study. Participants: Patients aged ≥18 years with episcleritis or scleritis seen at the Royal Victorian Eye and Ear Hospital from November 2014 to October 2015. Methods: Medical record review confirmed clinical diagnosis and characteristics. Incidence and prevalence were calculated using estimates of the adult population in areas of Melbourne with ≥30 ocular presentations/year to the emergency department. Main Outcome Measures: Diagnosis of active episcleritis or scleritis, aetiology, ocular complications and treatments. Results: From a general population of 3 408 068, we confirmed 149 new and 23 pre‐existing cases of active episcleritis, and 35 new and 23 pre‐existing cases of active scleritis. Incidence per 100 000 person‐years was 4.4 (95% confidence interval [CI] 3.7‐5.1) for episcleritis and 1.0 (95% CI 0.7‐1.4) for scleritis, while 12‐month prevalence was 5.1 (95% CI 4.3‐5.9) and 1.7 (1.3‐2.2) per 100 000 persons, respectively. Systemic disease was associated with 10% of episcleritis compared with 34% of scleritis (P <.001). Ocular complications were seen in 3% (6/184) of episcleritis eyes and 44% (32/72) of scleritis eyes, with the commonest being anterior uveitis (12/72) and ocular hypertension (14/72). At presentation, scleritis patients were commonly treated with oral non‐steroidal anti‐inflammatory drugs (60%) and prednisolone (19%). By 12 months, 24% of scleritis patients required immunosuppressants. Conclusions and Relevance: Rates of episcleritis and scleritis in our single‐centre Australian study were low. Episcleritis was usually benign, whereas scleritis had increased ocular complications and systemic disease. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) is a common and costly condition and a leading cause of disabilities across the globe. In Australia and other countries, there has been changes in LBP management guidelines and evidence in recent years, including the use of pharmacotherapy. Inadequately treated LBP is a burden with significant health and economic impacts. Although there is some variability, non-steroidal anti-inflammatory drugs (NSAIDs) have largely replaced paracetamol as the first-choice analgesic for non-specific LBP in many international clinical guidelines, including the current Australian Therapeutic Guidelines. More recent clinical evidence also supports that targeting LBP with the use of NSAIDs can provide superior and more effective relief of LBP symptoms compared with paracetamol. Community pharmacists are one of the most accessible and frequently visited health professionals that offer vital primary healthcare services aimed to provide enhanced clinical outcomes for patients. The position of a community pharmacist is pivotal in LBP assessment and management, from both a pharmacological and non-pharmacological standpoint, including the use of clinical guidelines, yet their roles are often not fully utilized in LBP therapy. Studies investigating the community pharmacist's views, practices, knowledge, and roles, specifically in LBP management in Australia are variable and limited. This narrative review will briefly cover the impacts of LBP, and to provide a summary on recent evidence, updates and a comparison of the Australian and international low back pain management guidelines on paracetamol vs NSAIDs in LBP, as well as pharmacists' roles and interventions in a primary healthcare setting in this context. [ABSTRACT FROM AUTHOR]

Purpose: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. Methods: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. Results: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. Conclusion: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress and inflammation are the underlying factors in many chronic debilitating diseases and commonly intertwined. Terminalia ferdinandiana is a traditional medicinal plant, endemic to Australia and is a rich source of many bioactive phytochemicals such as ellagic acid (EA) with known antioxidant capacity. Methods: We investigated the in vitro antioxidant and anti-inflammatory activity of an aqueous food grade EA enriched (EAE) extract of T. ferdinandiana. Caco-2 and KERTr cell lines were treated with EAE or pure EA (used as reference control), followed by the exposure to hydrogen peroxide (H2O2). Levels of reactive oxygen species (ROS) production and gene expression of molecular markers associated with oxidative stress and inflammation were monitored. Results: Significant reduction in ROS production was observed in both cell types treated with 100 or 200 µg/mL EA or EAE. Treatment of cells with EAE or EA showed upregulation of mRNA expression of the antioxidative gene superoxide dismutase (SOD)-2 and downregulated the expression of inducible nitric oxide synthase (iNOS), soluble cell adhesion molecule (sICAM), and cyclooxygenase (COX)-2. Neither EAE nor EA had any effect on the constitutively expressed COX1. Conclusions: The antioxidant and anti-inflammatory activity of T. ferdinandiana extract on mammalian cells exposed to H2O2 suggests the potential of using this traditional medicinal plant in preventing oxidative damage and inflammation related diseases. [ABSTRACT FROM AUTHOR]

Eucalyptus (Eucapyptus spp.), is a large genus of the Myrtaceae family, which includes 900 species and subspecies. This evergreen tall tree is native from Australia and Tasmania and is the second largest genera after acacia. In particular, the species E. globulus is widely used in the pulp industry, as well as for the production of eucalyptus oil extracted on a commercial scale in many countries as raw materials in perfumery, cosmetics, food, beverages, aromatherapy and phytotherapy. The 1,8-cineole (eucalyptol), isthe principal and the most important constituent extracted from eucalyptus leaves, demonstrates antimicrobial and anti-inflammatory activities. Despite the fact that the healthy effects of eucalyptus have been well established by research, further studies are necessary to investigate other prime effects of the plant and its possible implication in the treatment of a greater number of pathological conditions. [ABSTRACT FROM AUTHOR]

Summary: Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant. Objectives: To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes. Methods: We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self‐reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high‐risk (history of skin cancer excisions or more than five actinic lesions treated) and average‐to‐low‐risk participants (no history of skin cancer excision and at most five actinic lesions treated). Results: After a median of 3 years of follow‐up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high‐risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71–0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64–0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average‐to‐low‐risk participants. Conclusions: While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long‐term follow‐up may help us to comprehend the cumulative dose effect. What's already known about this topic? Recent meta‐analyses of observational studies and randomized controlled trials have suggested a potential benefit of nonsteroidal anti‐inflammatory drugs in reducing the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).However, there is substantial heterogeneity across studies. What does this study add? We used data from a large prospective cohort study specifically designed to study skin cancer.We found weak inverse and inconsistent associations between aspirin and nonaspirin NSAID use in the year before baseline and BCC and SCC incidence in the next 3 years.This suggests a limited role for NSAIDs as chemopreventive agents for keratinocyte cancers. Linked Editorial: Rundle and Dellavalle. Br J Dermatol 2019; 181:654–656. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Abstract The bioassay-guided isolation of new anti-inflammatory metabolites from the Australian Indigenous plant Angophora costata led to the discovery of three new 4-phenylcoumarins, costatamins A – C (1–3). The structures were determined by detailed spectroscopic analysis. Costatamins A – C were evaluated for their inhibitory effects on (a) NO production and (b) TNF-α release in RAW 264.7 macrophages, displaying an IC(50) value of 20–30 μg/mL for both the inflammatory markers. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Objectives Dental practitioners are able to prescribe a variety of medicines subsidized on the Pharmaceutical Benefits Schedule ( PBS), the main categories of which are analgesics and antibiotics. We aimed to investigate the patterns of PBS prescribing of non-antimicrobial medicines by dental practitioners in Australia from 2001 to 2012. Methods Data were collected from Medicare Australia on prescriptions from dental practitioners dispensed to concessional beneficiaries between 2001 and 2012. We examined patterns of use over time. Results There was an overall increase in number of prescriptions and in dispensed use (standardized by dose and population) of analgesic medicines for the concessional population over the 12-years period. The use of dentally prescribed analgesics increased 15%, with use of nonsteroidal anti-inflammatory drugs increasing by 41% and opioid analgesics by 12%. Prescribing of the oxycodone 5-mg tablet increased 344% between 2005 and 2012, and dental prescription of the benzodiazepines diazepam and temazepam increased by 51% and 229%, respectively, over the observation period. Injectable corticosteroid use increased by 19%. Conversely, use of carbamazepine and anti-emetics decreased by 39% and 10%, respectively. Conclusions Dental prescribing of analgesics, anti-inflammatories and benzodiazepines in the concessional population has increased significantly over the past decade. These data can form the baseline to further examine appropriate medicine use in the management of dental conditions. [ABSTRACT FROM AUTHOR]

Importance: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known.Objective: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis.Design, Setting, and Participants: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016).Interventions: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated.Main Outcomes and Measures: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death.Results: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%).Conclusions and Relevance: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up.Trial Registration: clinicaltrials.gov Identifier: NCT00132691. [ABSTRACT FROM AUTHOR]

Aim: The aetiology and clinical course of Bell's palsy may be different in paediatric and adult patients. There is no randomised placebo controlled trial (RCT) to show effectiveness of prednisolone for Bell's palsy in children. The aim of the study was to assess current practice in paediatric Bell's palsy in Australia and New Zealand Emergency Departments (ED) and determine the feasibility of conducting a multicentre RCT within the Paediatric Research in Emergency Departments International Collaborative (PREDICT).Methods: A retrospective analysis of ED medical records of children less than 18 years diagnosed with Bell's palsy between 1 January, 2012 and 31 December, 2013 was performed. Potential participants were identified from ED information systems using Bell's palsy related search terms. Repeat presentations during the same illness were excluded but relapses were not. Data on presentation, diagnosis and management were entered into an online data base (REDCap).Results: Three hundred and twenty-three presentations were included from 14 PREDICT sites. Mean age at presentation was 9.0 (SD 5.0) years with 184 (57.0%) females. Most (238, 73.7%) presented to ED within 72 h of symptoms, 168 (52.0%) had seen a doctor prior. In ED, 218 (67.5%) were treated with steroids. Prednisolone was usually prescribed for 9 days at around 1 mg/kg/day, with tapering in 35.7%.Conclusion: Treatment of Bell's palsy in children presenting to Australasian EDs is varied. Prednisolone is commonly used in Australasian EDs, despite lack of high-level paediatric evidence. The study findings confirm the feasibility of an RCT of prednisolone for Bell's palsy in children. [ABSTRACT FROM AUTHOR]

Background: Until June 2022, more than 540.9 million people had been diagnosed with COVID-19, and the pandemic had claimed more than six million lives worldwide. Two years after fighting the virus, we faced a more uncertain position. SARS-CoV-2 is constantly mutating and reappears regularly, particularly with Omicron variants showing high genetic variation and immune escape mechanisms. The efficacy and duration of protection of existing vaccines against new variants of SARS-CoV-2 remains uncertain. The world needs time to develop new variant-specific drugs, including monoclonal topics, vaccines, and other antiviral drugs, to fight the epidemic., Objective: The aim of this study was to illustrate the scientific, effective and systematic nature of three classical prescriptions of traditional Chinese medicine (TCM) for the treatment of COVID-19 through comparison of disease symptoms, diagnostic process, and treatment methods and evidence-based and pharmacological studies., Methods: We analysed the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia" (Version 9) made by China, "WHO-2019-nCoV-therapeutics", "Therapeutic Guidelines" published by Australian Therapeutic Guidelines Limited, "Shanghan Lun (Treatise on Febrile Diseases)", "Jinkui Yaolue (Golden Chamber Synopsis), and "Wenyi Lun (The Epidemic Febrile Disease)". We manually retrieved the dictionary of traditional Chinese medicine (Version II). In addition, we searched the Wiley online library, National Center for Biotechnology Information (NCBI), VIP, WHO website, and China National Knowledge Infrastructure (CNKI) for relevant literature from 2001 to 2022. We searched the original plants, ingredients, pharmacology, functions and indications, usage and dosage, drug efficacy, literature sources, and conduct an evidence-based studies. We quantified the strength of pharmacological action to show the pertinence of disease development., Results: We found that the diagnosis and treatment of pulmonary infection caused by epidemic disease in TCM classics is consistent with the diagnostic process of modern medical therapeutic guidelines. The three classic prescriptions have significant symptomatic therapeutic effects on the respiratory, gastrointestinal, urinary and hematological symptoms of the clinical manifestations of COVID-19. It was found that the herbal functional group of Houpo (Cortex Magnoliae Officinalis ), Chaihu ( Radix Bupleuri ), Cangzhu ( Rhizoma Atractylodis ), Qianghuo ( Notopterygii Rhizoma et Radix ), etc showed strong anti-inflammatory activity and had a positive effect on treating and preventing the outbreaks of systemic inflammatory factors., Conclusion: TCM can obtain obvious curative effect in symptomatic treatment, has strong anti-inflammatory effect, and can effectively reduce symptoms and patients' pain., Competing Interests: The authors declare no conflict of interest., (© 2023 Song D et al.)

Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson’s and Alzheimer’s disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50  5.57±1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL. [ABSTRACT FROM AUTHOR]

Background: Emu oil is a product of animal origin used for the treatment of inflammation, burns etc. as a part of aboriginal medicine in Australia. Crohn's disease is a common inflammatory manifestation in humans and other animal species relating to the ulceration and digestive disturbances in upper gastro-intestinal tract. Aloe vera is commonly used substance from plant sources for inflammation, wound healing and various other properties. Given the difference in the source of the substances all the while playing a similar therapeutic role in different parts of the world, the present investigation was undertaken to evaluate the protective effect of aloe vera and emu oil alone and in combination; in comparison to sulfasalazine (Allopathic drug) as an alternative for the treatment of Crohn's disease. Methods: Wistar albino rats were divided into six groups with two sub-groups of six animals each. After pre-treating the animals with sulfasalazine, aloe vera, emu oil and their combination for five consecutive days, the animals were sub-cutaneously administered indomethacin on 4th and 5th day and each sub-group was sacrificed on day 6 and 9. After sacrifice, serum and intestine of these animals was collected. Intestine length from duodenum till caecum was measured for estimating relative organ weight and disease activity index. Part of intestine was preserved in formalin for histopathology while the rest was used for analysis of oxidative parameters and myeloperoxidase. Serum collected was used for measuring alkaline phosphatase and cholesterol. Results: Assessment of the parameters in treatment groups indicated that the combination of aloe vera and emu oil resulted in better protection by suppressing the oxidative (P < 0.05) and histomorphological changes indicating a enhanced effect of these two agents which was found to be better than sulfasalazine. Conclusion: The combination of emu oil and aloe vera exhibited enhanced effect resulting in significant protection from indomethacin induced ulceration. This might be due to the different mechanism of anti-inflammatory effects (Salicylic acid in aloe vera and n3, n6 fatty acids acting as pseudosubstrates to cyclooxygenase enzyme) of components of the animal and plant products tested. [ABSTRACT FROM AUTHOR]

The article describes the case of a 26-year-old heterosexual man who presented with a1-week history of dysuria and urinary frequency. Topics covered include the medical history of the patient, the findings of laboratory examinations which led to the diagnosis of sexually acquired reactive arthritis secondary to macrolide-resistant urethritis, and patient outcome following treatment that include intravenous ceftriaxone, azithromycin and doxycycline.

Phytochemical investigation of the leaves of the Australian rainforest tree Cryptocarya mackinnoniana led to the discovery of three new oxygenated phenyl alkyl acids, cryptocaryoic acids A – C and two known compounds, cryptocaryone and 2′,6′-dihydroxy-4′-methoxychalcone. The structures of all the compounds were determined by detailed spectroscopic analysis. Mosher's analysis was used for absolute stereochemistry determination at C-11, while the remaining stereochemistry determination of the one remaining stereocenter C-13 was based on NOESY correlations. All compounds isolated were also evaluated for their anti-inflammatory properties by assessing their inhibitory effects on LPS and interferon-γ induced nitric oxide (NO) production and TNF- α release in RAW 264.7 macrophages. The new cryptocaryoic acids exhibited weak to moderate anti-inflammatory activity (NO inhibition) ranging from (18.4–56 μM). [Display omitted] • Three new phenyl alkyl acids, cryptocaryoic acids A – C, were isolated from the leaves of Cryptocarya mackinnoniana • Cryptocaryoic acids exhibited weak to moderate anti-inflammatory activity • Cryptocaryoic acids are the first in the series of molecules bearing the phenyl oxy-alkyl acid from C.mackinnoniana [ABSTRACT FROM AUTHOR]

Background Observational studies have reported survival benefits associated with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and non-aspirin NSAIDs (NA-NSAIDs), especially new use post-diagnosis, in women with ovarian cancer (OC). Methods Participants were women aged 18-79 diagnosed with OC in Australia, 2012-2015. Information was gathered through self-completed 3-monthly questionnaires and prescription records. Exposure was defined as any use (NA-NSAIDs/regular-dose aspirin □1/week or daily low-dose aspirin) during the year pre-diagnosis and first year post-diagnosis. We measured overall survival from start of primary treatment (surgery/neoadjuvant chemotherapy) (pre-diagnosis use) or from 12 months after the start of therapy (post-diagnosis) until the earliest of date of death/last follow-up/5 years. Cox proportional hazards regression was used to estimate survival. We also applied inverse-probability of treatment weighting (IPTW), which balances comparison groups regarding potential confounders. Results We observed improved survival associated with pre-diagnosis use of aspirin/NA-NSAIDs ≥4 days/week (frequent-users) compared to < 1/week (hazard ratio [HR] =0.72, 95% confidence interval [CI]=0.54-0.97). The association was close to null for those who used medications 1-3 days/week. Similarly, we saw a 30-40% improvement in survival associated with post-diagnosis aspirin/NA-NSAID use, again driven by frequent users (HR = 0.61, 95%CI=0.42-0.88). Results were similar when we excluded pre-diagnosis users, restricted to women who received chemotherapy, or assessed cancer-specific and progression-free survival. Results from IPTW models were similar to adjusted models. Conclusions Our findings suggest aspirin/NA-NSAID use might improve survival in women with OC. Larger cohorts or, preferably, a randomised controlled trial could clarify these findings. Key messages Use of aspirin/NA-NSAIDs may improve OC survival. [ABSTRACT FROM AUTHOR]

Background Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache. Objective To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids. Methods Participants with MOH who were using opioids were randomized via computer-generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double-blind, parallel groups study. Before randomization participants completed a 4-week baseline headache diary. During treatment, headache diary data collection continued and participants attended 4 study visits during which quantitative sensory testing was performed. Blood samples for immune biomarker analyses were collected before and after treatment in a subgroup of participants. Results Thirty-four participants were randomized, 13 of 15 randomized to ibudilast and 17 of 19 randomized to placebo completed treatment. Ibudilast was generally well-tolerated with mild, transient nausea reported as the most common adverse event (66.7% vs 10.5% in placebo group). Results are shown as mean (SD). At the end of treatment no differences in the primary outcome average daily headache index (placebo 62 [44] vs ibudilast 77 [72] groups, difference −15, CI −65 to 35 h × numerical rating scale), or secondary outcomes headache frequency (placebo 23 [8.1] vs ibudilast 24.5 [6.2], difference −1.5, CI −7.7 to 4.8 days/month) and opioid intake (placebo 20.6 [43] vs ibudilast 19 [24.3], difference 1.6, CI −31.5 to 34.8 mg morphine equivalent) were observed between placebo and ibudilast groups. Conclusions Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program. [ABSTRACT FROM AUTHOR]

Purpose: Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. In search of anti-inflammatory foods, we have systematically screened a variety of common dietary plants and mushrooms for their anti-inflammatory activity. Methods: A selection of 115 samples was prepared by a generic food-compatible processing method involving heating. These products were tested for their anti-inflammatory activity in murine N11 microglia and RAW 264.7 macrophages, using nitric oxide (NO) and tumour necrosis factor-α (TNF-α) as pro-inflammatory readouts. Results: Ten food samples including lime zest, English breakfast tea, honey-brown mushroom, button mushroom, oyster mushroom, cinnamon and cloves inhibited NO production in N11 microglia, with IC values below 0.5 mg/ml. The most active samples were onion, oregano and red sweet potato, exhibiting IC values below 0.1 mg/ml. When these ten food preparations were retested in RAW 264.7 macrophages, they all inhibited NO production similar to the results obtained in N11 microglia. In addition, English breakfast tea leaves, oyster mushroom, onion, cinnamon and button mushroom preparations suppressed TNF-α production, exhibiting IC values below 0.5 mg/ml in RAW 264.7 macrophages. Conclusion: In summary, anti-inflammatory activity in these food samples survived 'cooking'. Provided that individual bioavailability allows active compounds to reach therapeutic levels in target tissues, these foods may be useful in limiting inflammation in a variety of age-related inflammatory diseases. Furthermore, these foods could be a source for the discovery of novel anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Objective: The unknown aetiology of Serrated Polyposis Syndrome (SPS) impedes risk prediction and prevention. We investigated risk factors for SPS, overall and stratified by World Health Organization (WHO) 2010 clinical criteria and by colorectal cancer (CRC)., Method: A retrospective case-control study involving a cross-sectional analysis from 350 unrelated individuals with SPS from the Genetics of Colonic Polyposis Study and 714 controls from the Australasian Colorectal Cancer Family Registry. Univariate and multivariate logistic regression modelling was used to determine the association between risk factors and SPS and risk factors associated with CRC in SPS., Results: Female biological sex (odds ratio (OR) = 4.54; 95%Confidence interval (CI) = 2.77-7.45), increasing body mass index (BMI) at age 20 years (OR = 1.09; 95%CI = 1.04-1.13), hormone replacement therapy (OR = 0.44; 95%CI = 0.20.98), and increasing weekly folate intake (OR = 0.82; 95%CI = 0.75-0.90) were associated with SPS by multivariate analysis. Increasing weekly calcium intake (OR = 0.79; 95%CI = 0.64-0.97) and smoking > 10 cigarettes daily (OR = 0.45; 95%CI = 0.23-0.86) were associated with WHO criterion I only. The consumption of 1-100 g of alcohol per week (OR = 0.39; 95%CI = 0.18-0.83) was associated with WHO criterion III only. Smoking 1-5 cigarettes daily (OR = 2.35; 95%CI = 1.09-5.05), weekly non-steroidal anti-inflammatory drug (NSAIDs) intake (OR = 0.88; 95%CI = 0.78-0.99), and increased height (OR = 1.09; 95% = 1.05-1.13), were associated with SPS fulfilling both WHO criteria I and III. Moreover, weekly NSAIDs intake (OR = 0.81; 95%CI = 0.67-0.98) was associated with a reduced likelihood of CRC in SPS., Conclusion: We identified novel risk and potential protective factors associated with SPS, some specific for certain WHO 2010 criteria. Weekly use of NSAIDs may reduce the risk of CRC in people with SPS., (© 2022. The Author(s).)

Background: Around the turn of this century, the oil yield and chemical composition of Australian Leptospermum species was analysed. Since that time, research has been focused on their use as phytomedicines. The oil yield and composition of essential oils from Australian Leptospermum species directly impacts their commercialisation for medicinal use. Results: The essential oils from Leptospermum (L.) juniperinum, L. laevigatum, L. liversidgei, L. polygalifolium,L. semibaccatum, L. speciosum, L. trinervium and L. whitei have been examined from specimens in the Sunshine Coast (Queensland) and Northern Rivers (New South Wales) Regions. Both chemotypes of L. liversidgei were observed. However, only chemotype II of L. semibaccatum and chemotype I of L. trinervium were identified. The only subspecies observed of L. polygalifolium was L. polygalifolium wallum. Conclusions: L. liversidgei chemotypes I and II have the potential for phytomedical use as antibacterial or anti-inflammatory agents. Chemotype I has the potential for use as an insect repellent and chemotype II may provide antifungal activity [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to evaluate the predictive performances of all previously derived limited sampling strategies (LSSs) for total prednisolone, and to derive LSSs for free prednisolone in an independent cohort of adult kidney transplant recipients. Methods: Total and free prednisolone area under the concentration-time curve profiles from 0 to 12 hours post-dose (AUC) were collected from 20 subjects. All previously published total prednisolone LSSs were identified from the literature. Free prednisolone LSSs were developed using multiple linear regression analyses. AUC predicted by each of the LSSs was compared with AUC. Median percentage prediction error (MPPE) and median absolute percentage prediction error (MAPE) were calculated to evaluate bias and imprecision. Results: Total dose-adjusted prednisolone exposure varied 5-fold among study participants, while free dose-adjusted prednisolone exposure varied 3-fold. Correlation (r) between total and free prednisolone AUC was 0.79 ( p = <0.0001) for the entire study cohort. This correlation was poorer in those early compared with late post-transplant (r = 0.42 ( p = 0.04) versus r = 0.59 ( p = 0.009) respectively). Ten previously published LSSs for total prednisolone and 15 derived LSSs for free prednisolone performed with acceptable levels of bias and imprecision (<15%). Of the free prednisolone LSSs, an equation incorporating 0.25-, 2- and 4-h concentrations showed the highest predictive power (AUC = −17.20 + 1.18 × C + 2.75 × C + 4.45 × C; MPPE = 0.1%, MAPE = 4.6%). Conclusions: Wide between-subject variability in drug exposure suggests a role for TDM. LSSs can accurately estimate both total and free prednisolone AUC. However, given the poor correlation observed between the two parameters, our data suggest that free prednisolone LSSs may be preferable. [ABSTRACT FROM AUTHOR]

Objectives: Adult supraglottitis is a potentially life-threatening airway infection. We reviewed the management and outcome of supraglottitis in 169 adults admitted to Liverpool Hospital between 1999 and 2009. Methods: A retrospective review was conducted of all admissions with supraglottitis in patients at least 18 years of age. The diagnosis was confirmed by fiberoptic nasolaryngoscopy or direct laryngoscopy under general anesthesia. The main outcome measure was the need for intubation or tracheotomy. Univariate analysis was performed to determine factors that led to a worse outcome. Results: There were 80 men and 89 women in the cohort, with a median age of 51 years. Of these, 140 patients were admitted to the intensive care unit for a mean duration of 2 days. The common symptoms and signs at presentation were odynophagia and dysphagia (94%), dysphonia (65%), and stridor (33%). Endotracheal intubation was performed in 16 patients, and an awake tracheotomy was required in 4 patients. Dexamethasone acetate was used in 103 patients. Thirty-five patients had diabetes mellitus as a comorbidity. The presence of diabetes was predictive of the need for intubation or tracheotomy (p < 0.05), and the use of steroids was predictive of an intensive care unit stay of 24 hours or less (p < 0.05). Conclusions: Fiberoptic laryngoscopy is the gold standard for diagnosis of supraglottitis, and close airway monitoring is crucial. Conservative management of the airway is a viable option, but the presence of diabetes makes airway intervention more likely. The use of steroids aids in symptom alleviation and hastens resolution of airway swelling, with no negative sequelae. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Carpobrotus rossii (CR) has a history of use as a food and therapeutic agent by Australian indigenous peoples and early European settlers and is believed to contain a number of pharmacologically active polyphenolic compounds. Aims of the study: Oxidation of low density lipoprotein (LDL), platelet aggregation, and inflammation contribute to the development and progression of atherosclerosis. The aim of the present study was to investigate the antioxidant, antiplatelet and anti-inflammatory activity of CR extract using human blood components. Materials and methods: An assay employing in vitro copper-induced oxidation of serum lipids was used to assess antioxidant activity of CR extract (and tannin, flavonoid and pre- and post-flavonoid fractions). The effects of CR extract on ADP- and collagen-induced platelet aggregation, and on basal (unstimulated) and lipopolysaccharide (LPS)- and phytohaemagglutinin A (PHA)-stimulated cytokine release from peripheral blood mononuclear cells (PBMC) were also investigated. Results: CR extract increased the lag time of serum oxidation (maximum of ∼4-fold at 20μg/ml) in a concentration-dependent manner. The antioxidant activity resided only in the tannin and post-flavonoid fractions. CR had no effect on ADP-induced platelet aggregation, but significantly decreased collagen-induced platelet aggregation. LPS, but not PHA, significantly increased the release of IL-1β and TNF-α from PBMC. CR extract alone inhibited monocyte chemoattractant protein (MCP)-1 release and in the presence of LPS, inhibited IL-10, TNF-α and MCP-1 release compared to LPS alone. Conclusion: CR has significant in vitro antioxidant, antiplatelet and, potentially, anti-inflammatory activity. [Copyright &y& Elsevier]

Ethnopharmacological relevance: Extracts of the medicinal plant species Dodonaea polyandra were investigated as part of a collegial research partnership between Northern Kaanju traditional owners represented by Chuulangun Aboriginal Corporation (centred on the Wenlock and Pascoe Rivers, Cape York Peninsula, Queensland, Australia) and university-based researchers. D. polyandra, known as “Uncha” in Kaanju language, is used in Northern Kaanju Traditional Medicine for relief from pain associated with toothache and related ailments. The species has a restricted distribution in Cape York Peninsula and there has been no previous Western scientific investigation of its pharmacology or chemistry. Aim of the study: The current study investigates the anti-inflammatory effects of several extracts from D. polyandra. Materials and methods: Phytochemical screening was conducted using TLC. Anti-inflammatory effects of leaf extracts were determined using an acute mouse ear oedema model induced by croton oil and 12-o-tetradecanoylphorbol-13-acetate (TPA) chemical irritants. Results: Flavonoid and terpenoid secondary compounds were detected in leaf extracts of D. polyandra. Non-polar hexane and methylene chloride/methanol extracts showed potent inhibition of inflammation in TPA-induced mouse ear oedema by 72.12 and 79.81%, respectively, after 24h at 0.4mg/ear. Conclusion: In a mouse model of acute inflammation, this study revealed that leaf extracts of D. polyandra possess significant anti-inflammatory potential. These results contribute to a Western scientific understanding of the ethnopharmacological use of the plant in Northern Kaanju Medicine for reducing tooth-related pain. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Current evidence suggests the use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of myocardial infarction and heart failure. However, some studies have failed to demonstrate a significant relationship. • Differences in patient demographics, study design, and the varying types and classes of NSAIDs studied might either confound or modify the association between NSAID use and risk of myocardial infarction and heart failure, and prevent accurate data interpretation. WHAT THIS STUDY ADDS • NSAID use is not associated with an increased risk of either incident myocardial infarction or heart failure in elderly patients. • NSAID use is associated with a reduction in all-cause mortality in this cohort. AIMS We studied the association between either non-selective NSAIDs (ns-NSAIDs), selective COX-2 inhibitors, or any NSAID and risk of incident myocardial infarction (MI) and heart failure (HF), and all-cause mortality in elderly subjects. METHODS We conducted a retrospective nested case-control study on Australian veterans using nationwide hospital admission and pharmacy dispensing data. We estimated adjusted odds ratios (OR) with 95% confidence intervals (CI) for the risk of events for three different measures of prescription supply exposure over the last 2 years: (i) supplied at least once, (ii) supply frequency: supplied more than twice within the last 30 days, once or twice within the last 30 days, and once or more 30 days to 2 years and (iii) total supplies. RESULTS We identified 83 623 cases and 1 662 099 matched controls (1:20) contributing 3 862 931 persons-years of observation. NSAID use at least once within the last 2 years did not significantly affect the risk of MI (OR 1.00, 95% CI 0.96, 1.04) but was associated with a mildly reduced risk of HF (OR 0.95, 95% CI 0.92, 0.98). There was a reduced all-cause mortality with at least one supply of either ns-NSAIDs (OR 0.94, 95% CI 0.90, 0.97), selective COX-2 inhibitors (OR 0.90, 95% CI 0.88, 0.93), or any NSAID (OR 0.87, 95% CI 0.85, 0.90). Risk of death was also inversely associated with the number of prescription supplies. CONCLUSIONS NSAID use is not associated with an increased risk of incident MI and HF but is associated with a reduction in all-cause mortality in Australian veterans. [ABSTRACT FROM AUTHOR]

In this comprehensive commentary, Australian essential oils and their components are listed and discussed in the context of their value to industry and aesthetics. The historic and cultural significance of endemic essential oils is explained. Several promising candidates are identified that have commercial potential and will enter the marketplace in the not-too-distant future. This text elaborates on the current progress in research, and explains the up-to-date view of 'bioactive,' with reference to insect repellence, antimicrobial activity, anti-inflammatory activity, and potential toxicity. The concept of chemotypes and chemophenetics is explained in detail to justify why chemically variable species in Australia require standardisation practices to ensure reproducibility of their derived natural products: standardisation practice includes cultivar development and authentication protocols. Thereafter, some of the more significant essential oils are defined and some background information provided. This review concludes with a comprehensive table of aromatic species that were studied by Joseph Brophy over the last 30 years, thereby providing the most comprehensive overview available, on the chemistry of Australian essential oil yielding species. [ABSTRACT FROM AUTHOR]

Prescribers in rural and remote locations perceive that there are different influences on their prescribing compared with those experienced by urban prescribers. The aim of this study was to compare the motivations and perceived influences on general practitioners (GPs) when prescribing COX-2 inhibitors rather than conventional non-steroidal anti-inflammatory drugs (NSAIDs) between rural and urban-based GPs in Queensland, Australia. A questionnaire was administered to two geographically distinct groups of GPs, one urban ( n = 67) and one rural ( n = 67), investigating the reasons that the GP would prescribe a COX-2 inhibitor rather than a conventional NSAID or vice versa and also focusing on patients requesting a prescription for a COX-2 inhibitor. A 51% response rate ( n = 68) was achieved. The difference between the rural and the urban GPs was that the urban GPs were more likely to perceive that they were influenced to prescribe COX-2 inhibitors by their patients’ knowledge of these new (at the time) drugs. GPs in both the rural and urban areas perceived the COX-2 selective inhibitors to be safer than conventional NSAIDs, and that there was little difference in terms of efficacy between the two drug classes. However, GPs from both of the study areas stated that conventional NSAIDs were preferred over COX-2 selective inhibitors, primarily due to their expense, if their patients were not at risk for developing a GI bleed. The motivations and perceived influences to prescribe a COX-2 inhibitor in rural and in urban areas of Queensland, Australia were very similar. Almost all surveyed GPs in rural and urban areas had patients request a prescription, or enquire about the COX-2 inhibitors. Urban GPs were more likely to feel pressured to prescribe a COX-2 inhibitor than their rural counterparts, agreeing with other research which found that patient pressure to prescribe appears to be greater in urban general practice. [ABSTRACT FROM AUTHOR]

Background: Cyclooxygenase (COX)-2 is a key inducible enzyme that regulates the production of anti-inflammatory prostaglandin E,. A single-nucleotide polymorphism, - 765G > C, located within a stimulatory protein-l binding site in the COX-2 promoter region, has been shown to have significantly lower promoter activity in vitro compared with the wild-type and was associated with decreased plasma levels of C-reactive protein after coronary artery bypass surgery. We hypothesized that this polymorphism, which may result in decreased COX-2 transcription, could be associated with more severe asthma, and/or aspirin-intolerant asthma (AlA). Objective: To determine the association between the -765G> C COX-2 polymorphism and asthma, disease severity and AlA in a large, well-phenotyped Australian population. Methods: PCR and restriction fragment length polymorphism analysis was used to characterize the polymorphism in an Australian Caucasian population of patients with mild (n = 322), moderate (n = 254) or severe (n = 88) asthma and in non-asthmatic control subjects (n = 512), as well as in patients with AlA (n = 58). Genotype and allele association analyses were performed using X² tests. Results The polymorphic -765C allele was present in approximately 30% of asthmatic patients and non-asthmatic controls. There was no association between the - 765G > C polymorphism and asthma (P = 0.920), disease severity (P = 0.840), atopy (P = 0.655) or AlA (P = 0.841) in this population. Conclusion Although the - 765G > C polymorphism may have lower promoter activity and result in decreased COX-2 expression, it is not associated with asthma, disease severity, AlA or atopy in this Australian population. [ABSTRACT FROM AUTHOR]