ORCID Profile
0000-0002-6822-7936
Current Organisations
Monash University
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 21-10-2019
Publisher: Wiley
Date: 11-01-2023
DOI: 10.1111/DOM.14953
Abstract: Early and intensive management of type 2 diabetes has been shown to delay disease progression, reduce the risk of cardiorenal complications and prolong time to treatment failure. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are being increasingly recognized for their potential in early disease management, with recent guideline updates recommending second‐line use of this injectable drug class alongside oral glucose‐lowering drugs. GLP‐1RAs target at least six of the eight core defects implicated in the pathogenesis of type 2 diabetes and offer significant glycaemic and weight‐related improvements over other second‐line agents in head‐to‐head trials. In addition, placebo‐controlled clinical trials have shown cardiovascular protection with GLP‐1RA use. Even so, this therapeutic class is underused in primary care, largely owing to clinical inertia and patient‐related barriers to early intensification with GLP‐1RAs. Fortunately, clinicians can overcome barriers to treatment acceptance through patient education and training, and management of treatment expectations. In this review we comment on global and Australian guideline updates and evidence in support of early intensification with this therapeutic class, and provide clinicians with practical advice for GLP‐1RA use in primary care.
Publisher: Public Library of Science (PLoS)
Date: 10-11-2022
DOI: 10.1371/JOURNAL.PONE.0276396
Abstract: Indigenous peoples in high income countries are disproportionately affected by Type 2 Diabetes. Socioeconomic disadvantages and inadequate access to appropriate healthcare are important contributors. This systematic review investigates effective designs of primary care management of Type 2 Diabetes for Indigenous adults in Australia, Canada, New Zealand, and the United States. Primary outcome was change in mean glycated haemoglobin. Secondary outcomes were diabetes-related hospital admission rates, treatment compliance, and change in weight or Body Mass Index. Included studies were critically appraised using Joanna Briggs Institute appraisal checklists. A mixed-method systematic review was undertaken. Quantitative findings were compared by narrative synthesis, meta-aggregation of qualitative factors was performed. Seven studies were included. Three reported statistically significant reductions in means HbA1c following their intervention. Seven components of effective interventions were identified. These were: a need to reduce health system barriers to facilitate access to primary care (which the other six components work towards), an essential role for Indigenous community consultation in intervention planning and implementation, a need for primary care programs to account for and adapt to changes with time in barriers to primary care posed by the health system and community members, the key role of community-based health workers, Indigenous empowerment to facilitate community and self-management, benefit of short-intensive programs, and benefit of group-based programs. This study synthesises a decade of data from communities with a high burden of Type 2 Diabetes and limited research regarding health system approaches to improve diabetes-related outcomes. Policymakers should consider applying the seven identified components of effective primary care interventions when designing primary care approaches to mitigate the impact of Type 2 Diabetes in Indigenous populations. More robust and culturally appropriate studies of Type 2 Diabetes management in Indigenous groups are needed. Registered with PROSPERO (02/04/2021: CRD42021240098 ).
Publisher: Informa UK Limited
Date: 28-07-2019
DOI: 10.1080/14739879.2019.1623087
Abstract: The James Cook University (JCU) medical school has a mission to produce doctors who are willing to work across northern Australia and may choose generalist rather than specialist careers. In addition to real-life placements in primary healthcare settings, the medical school has developed simulated General Practice (GP) clinics (simGPclinic) for Year 5 (Y5) students. This study compares the simGPclinic with actual GP placements for authenticity, teaching clinical skills, and preparation for real-life primary healthcare settings. Y5 students were administered a survey following their simGPclinic (n = 65 response rate = 97%). Students rated the simGPclinic's authenticity as 77 out of 100, and were more likely to rate the simGPclinic as being 'better' than their real-life GP placement in teaching them to: 'formulate a medical management plan and order correct pathology tests' 'rule out the "red flags" for the key clinical problem' 'undertake a patient-centred history and examination' 'make a differential diagnosis for the key clinical problem' and, 'develop communications skills'. The simGPclinic provided medical students with authentic and positive learning experiences in primary healthcare that were at least as beneficial as those provided in real-life settings, as well as being more reliable and better structured.
Publisher: Wiley
Date: 05-07-2021
DOI: 10.1002/EHF2.13483
Abstract: To systematically review randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)‐derived evidence for SGLT2i efficacy mechanisms in heart failure (HF). Systematic searches of Medline and Embase were performed. In seven trials [3730–17 160 patients low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type‐2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56–105 patients low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N‐terminal pro B‐type natriuretic peptide levels significant reductions vs. placebo were reported after 8–12 months (two studies 3730–4744 patients) but not ≤12 weeks (three studies 80–263 patients). Limited available RCT‐derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics. Sodium–glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis‐driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.
Publisher: Wiley
Date: 21-10-2014
DOI: 10.1007/S11745-014-3954-Z
Abstract: Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP-1 monocytes and adherent THP-1 cells were compared with other C18 fatty acids, LA and α-linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9-HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9-HODE and 13-HODE (but not LA or ALA) markedly increased caspase-3/7 activity (p < 0.001) in both monocytes and adherent THP-1 cells, with 9-HODE the more potent. In addition, 9-HODE and 13-HODE both increased Annexin-V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1 μM), but the effect of HODEs was replicated with apoptosis-inducer c tothecin (10 μM). Only 9-HODE increased DNA fragmentation. The pro-apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD-CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ-regulated apoptotic effects induced by 9-HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9-HODE and 13-HODE are potent--and specific--regulators of apoptosis in THP-1 cells. Their action is PPARγ-dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2019
Publisher: Springer Science and Business Media LLC
Date: 15-07-2014
Abstract: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor--HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3. SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not with trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion. SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.
Publisher: Informa UK Limited
Date: 19-02-2018
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
Publisher: Rural and Remote Health
Date: 12-01-2018
DOI: 10.22605/RRH3899
No related grants have been discovered for Roy Rasalam.