ORCID Profile
0000-0002-1456-876X
Current Organisations
Flinders University
,
UNSW Sydney
,
St Vincent's Hospital Sydney
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 07-2008
Publisher: Wiley
Date: 05-05-2022
DOI: 10.1002/JPPR.1810
Publisher: Wiley
Date: 24-01-2013
Publisher: Wiley
Date: 05-08-2021
DOI: 10.1111/BCP.14496
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.TIPS.2014.05.006
Abstract: Opioids, local anesthetics, anticonvulsant drugs, antidepressants, and non-steroidal anti-inflammatory drugs (NSAIDs) are used to provide pain relief but they do not provide adequate pain relief in a large proportion of chronic pain patients and are often associated with unacceptable side effects. Inhibitory glycinergic neurotransmission is impaired in chronic pain states, and this provides a novel target for drug development. Inhibitors of the glycine transporter 2 (GlyT2) enhance inhibitory neurotransmission and show particular promise for the treatment of neuropathic pain. N-arachidonyl-glycine (NAGly) is an endogenous lipid that inhibits glycine transport by GlyT2 and also shows potential as an analgesic, which may be further exploited in drug development. In this review we discuss the role of glycine neurotransmission in chronic pain and future prospects for the use of glycine transport inhibitors in the treatment of pain.
Publisher: Wiley
Date: 02-2023
DOI: 10.1111/BCP.15668
Abstract: Dose‐prediction software is recommended to enable area under the curve over 24 h (AUC 24 )‐guided dosing of the antibiotic vancomycin. However, uncertainty remains about how best to implement software in the clinic. We describe the activity, over 18 months, of a consultative therapeutic drug monitoring Advisory Service (the Service) for vancomycin that used dose‐prediction software alongside clinical expertise, identifying factors that influence attainment of therapeutic targets. Of the 408 vancomycin dose reports provided for 182 courses of therapy, most (57%) recommended a dose change. The majority (82.8%, 193/233) of recommended dose adjustments were accepted by treating teams. A dose report was not published for 125 courses of therapy, with reasons including patient in intensive care unit or service error. An estimated 26.6 h of staff time was allocated to Service activities each month. Publication of a dose report facilitated attainment of therapeutic targets ( P = .002). Software integration could improve Service outcomes, avoiding errors and reducing staff workload.
Publisher: Elsevier BV
Date: 2008
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.NEUINT.2013.08.012
Abstract: Glycine plays a key role in regulating inhibitory neurotransmission in the spinal cord and concentrations of glycine in the CNS are regulated by two subtypes of high affinity glycine transporters, GlyT1 and GlyT2. In this mini review we will discuss a series of lipid inhibitors of GlyT2 that show promise as analgesics in the treatment of neuropathic and inflammatory pain. N-arachidonyl-glycine inhibits the rate of transport by GlyT2, but has very little or no activity on GlyT1. We will discuss structure-activity studies of the actions of related lipids on GlyT2 and also the characterization of a more potent lipid inhibitor of GlyT2, oleoyl-l-carnitine. Both N-arachidonyl-glycine and oleoyl-l-carnitine show specificity for GlyT2 over GlyT1, which has allowed the use of chimeric GlyT1/GlyT2 transporters to begin characterizing the molecular basis for specificity and mechanism of action of these lipid inhibitors. Although our understanding of the molecular basis for lipid inhibition is still in its infancy, it appears that extracellular loop 4 of GlyT2 plays an important role in the inhibitory mechanism.
Publisher: Wiley
Date: 09-11-2017
DOI: 10.1111/DOM.12806
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-07-2018
DOI: 10.2215/CJN.05150418
Abstract: A change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between in iduals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug’s properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.
Publisher: Springer Science and Business Media LLC
Date: 03-03-2010
DOI: 10.1007/S00424-010-0792-6
Abstract: The functional role of ligand-gated ion channels in the central nervous system depends on their relative anion-cation permeability. Using standard whole-cell patch cl measurements and NaCl dilution potential measurements, we explored the effect of external alent ions on anion-cation selectivity in alpha1-homomeric wild-type glycine receptor channels. We show that increasing external Ca(2+) from 0 to 4 mM resulted in a sigmoidal increase in anion-cation permeability by 37%, reaching a maximum above about 2 mM. Our accurate quantification of this effect required rigorous correction for liquid junction potentials (LJPs) using ion activities, and allowing for an initial offset potential. Failure to do this results in a considerable overestimation of the Ca(2+)-induced increase in anion-cation permeability by almost three-fold at 4 mM external Ca(2+). Calculations of LJPs (using activities)_ were validated by precise agreement with direct experimental measurements. External SO (4) (2-) was found to decrease anion-cation permeability. Single-channel conductance measurements indicated that external Ca(2+) both decreased Na(+) permeability and increased Cl(-) permeability. There was no evidence of Ca(2+) changing channel pore diameter. Theoretical modeling indicates that the effect is not surface charge related. Rather, we propose that, under dilution conditions, the presence of an impermeant Ca(2+) ion in the channel pore region just external to the selectivity filter tends to electrostatically retard outward movement of Na(+) ions and to enhance movement of Cl(-) ions down their energy gradients.
Publisher: American Medical Association (AMA)
Date: 10-2018
Publisher: Wiley
Date: 05-11-2023
DOI: 10.1002/JPPR.1841
Abstract: Doctors are perceived as the primary decision makers in antimicrobial therapy, but prescribing decisions are influenced by the multidisciplinary team. Antimicrobial stewardship (AMS) programs formalise interprofessional advice‐giving. No studies capture the advice provided by pharmacists. This study aimed to describe the volume and nature of antimicrobial prescribing advice that healthcare professionals seek from hospital pharmacists. A prospective audit of antimicrobial‐related advice requests received by pharmacists ( n = 18) at an Australian public hospital was undertaken in July 2020. Antimicrobial advice was sought from 11 pharmacists on 300 occasions. Most requests (80%) were received by the AMS pharmacist. A mean (range) of 30 (17–40) requests per day was recorded and the AMS pharmacist received 24 (16–31) requests daily. Most requests came from the intensive care unit (22.1%), pharmacy (21.4%), and infectious diseases (17.1%). The AMS pharmacist was mostly contacted by consultants and pharmacists, and other pharmacists were contacted by registrars and junior medical officers. Despite COVID‐19 adaptations, face‐to‐face interaction was most common. This audit demonstrates the value of an AMS pharmacist, and indicates the importance of face‐to‐face interactions and the formalisation of pharmacists' role in prescribing decision‐making. Pharmacists provided antimicrobial advice daily to other healthcare professionals. Further research is required to provide insights into the barriers and enablers to effective advice‐giving interactions.
Publisher: Wiley
Date: 27-10-2022
DOI: 10.1111/BCP.15091
Abstract: Identification of the most appropriate population pharmacokinetic model‐based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially, necessitating dose adjustments. Population pharmacokinetic models of tacrolimus were selected ( n = 17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate‐release formulation of tacrolimus (Prograf) were obtained up to 391 days post‐transplant. The performance of each model was evaluated using: (i) prediction‐based assessment (bias and imprecision) of the in idual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL = 0, FOCE‐I) from 1–3 prior dosing occasions and (ii) simulation‐based assessment (prediction‐corrected visual predictive check). Both assessments were stratified based on concomitant azole antifungal use. Regardless of the number of prior dosing occasions (1–3) and concomitant azole antifungal use, all models demonstrated unacceptable in idual predicted tacrolimus concentration of the fourth dosing occasion ( n = 152). The prediction‐corrected visual predictive check graphics indicated that these models inadequately predicted observed tacrolimus concentrations. All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.
Publisher: American Chemical Society (ACS)
Date: 03-05-2012
DOI: 10.1021/CN3000229
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-06-2018
DOI: 10.2215/CJN.00340118
Publisher: Wiley
Date: 15-04-2021
DOI: 10.1111/BCP.14844
Abstract: Accurate documentation of medication administration time is imperative for many therapeutic decisions, including dosing of intravenous antimicrobials. The objectives were to determine (1) the discrepancy between actual and documented administration times for antimicrobial infusions and (2) whether day of the week, time of day, nurse‐to‐patient ratio and drug impacted accuracy of documented administration times. Patient and dosing data were collected (June–August 2019) for 55 in‐patients receiving antimicrobial infusions. “Documented” and “actual” administration times ( n = 660) extracted from electronic medication management systems and smart infusion pumps, respectively, were compared. Influence of the day (weekday/weekend), time of day (day/evening/night), nurse‐to‐patient ratio (high 1:1/low 1:5) and drug were examined. Monte Carlo simulation was used to predict the impact on dose adjustments for vancomycin using the observed administration time discrepancies compared to the actual administration time. The median discrepancy between actual and documented administration times was 16 min (range, 2–293 min), with discrepancies greater than 60 minutes in 7.7% of administrations. Overall, discrepancies (median [range]) were similar on weekends (17 [2–293] min) and weekdays (16 [2–188] min), and for high (16 [2–157] min) and low nurse‐to‐patient ratio wards (16 [2–293] min). Discrepancies were smallest for night administrations ( P .05), and antimicrobials with shorter half‐lives ( P .0001). The observed discrepancies in vancomycin administration time resulted in a different dose recommendation in 58% of cases (30% higher, 28% lower). Overall, there were discrepancies between actual and documented antimicrobial infusion administration times. For vancomycin, these discrepancies in administration time were predicted to result in inappropriate dose recommendations.
Publisher: Informa UK Limited
Date: 20-12-2017
DOI: 10.1080/17425255.2017.1269745
Abstract: Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol. Significant aspects discussed are the importance of adherence to allopurinol therapy, allopurinol hypersensitivity reactions and insights into hyperuricemia. Expert opinion: The initial dosage of allopurinol should be low, particularly in patients with renal impairment. The dose should then be increased slowly until plasma concentrations of urate are sufficient to dissolve monosodium urate crystals (≤ 0.36 mmol/L). For this target, the maintenance dose of allopurinol can be estimated from the equation: Dose = 1413*(U
Publisher: Portland Press Ltd.
Date: 10-2006
DOI: 10.1042/BST0340882
Abstract: Nicotinic ACh (acetylcholine) and 5-HT3 (5-hydroxytryptamine type-3) receptors are cation-selective ion channels of the Cys-loop transmitter-gated ion channel superfamily. Numerous lines of evidence indicate that the channel lining domain of such receptors is formed by the α-helical M2 domain (second transmembrane domain) contributed by each of five subunits present within the receptor complex. Specific amino acid residues within the M2 domain have accordingly been demonstrated to influence both single-channel conductance (γ) and ion selectivity. However, it is now clear from work performed on the homomeric 5-HT3A receptor, heteromeric 5-HT3A/5-HT3B receptor and 5-HT3A/5-HT3B receptor subunit chimaeric constructs that an additional major determinant of γ resides within a cytoplasmic domain of the receptor termed the MA-stretch (membrane-associated stretch). The MA-stretch, within the M3–M4 loop, is not traditionally thought to be implicated in ion permeation and selection. Here, we describe how such observations extend to a representative neuronal nicotinic ACh receptor composed of α4 and β2 subunits and, by inference, probably other members of the Cys-loop family. In addition, we will attempt to interpret our results within the context of a recently developed atomic scale model of the nicotinic ACh receptor of Torpedo marmorata (marbled electric ray).
Publisher: Elsevier BV
Date: 11-2013
Publisher: Wiley
Date: 25-04-2023
DOI: 10.1111/BCP.15737
Abstract: This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin naïve. Two prospective studies on heart failure patients were undertaken. The first was a cross‐sectional study with two patient cohorts, one with T2DM on metformin (n = 44) and one without T2DM metformin naive (n = 47). The second was a 12‐week interventional study of patients without T2DM (n = 27) where metformin (500 mg immediate release, twice daily) was prescribed. Plasma metformin and lactate concentrations were monitored. In idual pharmacokinetics were compared between cohorts. Univariable and multivariable analysis analysed the effects of variables on plasma lactate concentrations. Plasma metformin and lactate concentrations mostly (99.9%) remained below safety thresholds (5 mg/L and 5 mmol/L, respectively). Metformin concentration had no significant relationship with lactic acidosis safety markers. In the interventional study, New York Heart Association (NYHA) II ( P .03) and III ( P .001) grading was associated with higher plasma lactate concentrations, whereas male sex was associated with 47% higher plasma lactate concentrations ( P .05). The pharmacokinetics of heart failure patients with and without T2DM were similar. We observed no unsafe plasma lactate concentrations in patients with heart failure treated with metformin. Metformin exposure did not influence plasma lactate concentrations, but NYHA class and sex did. The pharmacokinetics of metformin in heart failure patients are similar irrespective of T2DM. These findings may support the safe use of metformin in heart failure patients with and without T2DM.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2021
DOI: 10.1097/FTD.0000000000000909
Abstract: Therapeutic drug monitoring is recommended to guide tacrolimus dosing because of its narrow therapeutic window and considerable pharmacokinetic variability. This study assessed tacrolimus dosing and monitoring practices in heart transplant recipients and evaluated the predictive performance of a Bayesian forecasting software using a renal transplant–derived tacrolimus model to predict tacrolimus concentrations. A retrospective audit of heart transplant recipients (n = 87) treated with tacrolimus was performed. Relevant data were collected from the time of transplant to discharge. The concordance of tacrolimus dosing and monitoring according to hospital guidelines was assessed. The observed and software-predicted tacrolimus concentrations (n = 931) were compared for the first 3 weeks of oral immediate-release tacrolimus (Prograf) therapy, and the predictive performance (bias and imprecision) of the software was evaluated. The majority (96%) of initial oral tacrolimus doses were guideline concordant. Most initial intravenous doses (93%) were lower than the guideline recommendations. Overall, 36% of initial tacrolimus doses were administered to transplant recipients with an estimated glomerular filtration rate of mL/min/1.73 m despite recommendations to delay the commencement of therapy. Of the tacrolimus concentrations collected during oral therapy (n = 1498), 25% were trough concentrations obtained at steady-state. The software displayed acceptable predictions of tacrolimus concentration from day 12 (bias: −6% 95%confidence interval, −11.8 to 2.5 imprecision: 16% 95% confidence interval, 8.7–24.3) of therapy. Tacrolimus dosing and monitoring were discordant with the guidelines. The Bayesian forecasting software was suitable for guiding tacrolimus dosing after 11 days of therapy in heart transplant recipients. Understanding the factors contributing to the variability in tacrolimus pharmacokinetics immediately after transplant may help improve software predictions.
Publisher: Wiley
Date: 02-2019
DOI: 10.1002/JPPR.1511
Publisher: Public Library of Science (PLoS)
Date: 23-06-2016
Publisher: Springer Science and Business Media LLC
Date: 28-07-2018
DOI: 10.1007/S00228-018-2525-2
Abstract: Audit studies reveal frequent non-compliance with dosing and monitoring guidelines for vancomycin. This study aimed to qualitatively explore the barriers and facilitators of compliance with vancomycin dosing and monitoring guidelines. Interviews were conducted with 16 prescribers in a large tertiary teaching hospital in Sydney, Australia. Questions explored knowledge, attitudes, and perceived complexities associated with vancomycin use. Interviews were analysed using thematic analysis. Prescribers reported utilising vancomycin guidelines, citing familiarity with guidelines, a positive perception of guidelines, awareness of poor guideline compliance, and assistance from specialist staff as facilitators of the uptake of guideline recommendations. Barriers existing within the prescribing environment such as the prescribing culture, a lack of time, and poor communication and coordination of therapeutic drug monitoring processes were identified as hindrances to guideline compliance. The provision of guidelines may not be sufficient in ensuring appropriate prescribing and monitoring of vancomycin when barriers relating to the prescribing environment exist. Developing interventions targeted toward these barriers, such as having dedicated phlebotomists for vancomycin blood s ling, fostering better handover processes, and educating staff on poorly understood aspects of guidelines, is likely to improve the uptake of guideline recommendations for vancomycin and other medications requiring therapeutic drug monitoring.
Publisher: Informa UK Limited
Date: 21-10-2023
Publisher: Elsevier BV
Date: 03-2006
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.BMC.2005.04.054
Abstract: Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the alpha7 nAChR subtype.
Publisher: Elsevier BV
Date: 12-2004
Publisher: Wiley
Date: 14-04-2021
DOI: 10.1111/BCP.14834
Abstract: Despite the availability of international consensus guidelines, vancomycin dosing and therapeutic drug monitoring (TDM) remain suboptimal. This study aimed to assess concordance of vancomycin dosing and TDM with institutional guidelines and to identify factors taken into consideration by clinicians when prescribing vancomycin. A retrospective audit of 163 patients receiving vancomycin therapy (≥48 hours) was undertaken. Data collected included patient characteristics, dosing history and plasma vancomycin and creatinine concentrations. Concordance of dosing and TDM with institutional guidelines was evaluated. Semi‐structured interviews, including simulated prescribing scenarios, were undertaken with prescribers ( n = 17) and transcripts analysed. Plasma vancomycin concentrations ( n = 1043) were collected during 179 courses of therapy. Only 24% of courses commenced with a loading dose with 72% lower than recommended. The initial maintenance dose was concordant in 42% of courses with 34% lower than recommended. Only 14% of TDM s les were trough vancomycin concentrations. Dose was not adjusted for 60% (21/35) of subtherapeutic and 43% (18/42) of supratherapeutic trough vancomycin concentrations, respectively. Interview participants reported that patient characteristics (including renal function), vancomycin concentrations, guidelines and expert advice influenced vancomycin prescribing decisions. Despite referring to guidelines when completing simulated prescribing scenarios, only 37% of prescribing decisions aligned with guideline recommendations. Poor compliance with institutional vancomycin guidelines was observed, despite prescriber awareness of available guidelines. Multifaceted strategies to support prescriber decision‐making are required to improve vancomycin dosing and monitoring.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2014
DOI: 10.1007/S12031-014-0322-7
Abstract: Experimental evidence suggests that GABA ρ1 receptors are potential therapeutic targets for the treatment of a range of neurological conditions, including anxiety and sleep disorders. Homology modelling of the GABA ρ1 extracellular N-terminal domain has revealed a novel hydrophobic area that extends beyond, but not including the GABA-binding site. Phenylalanine 124 (F124) is predicted to be involved in maintaining the structural integrity of the orthosteric-binding site. We have assessed the activity of a series of GABA ρ1 receptors that incorporate a mutation at F124. Wild-type and mutant human GABA ρ1 subunits were expressed in Xenopus laevis oocytes and AD293 cells, and the pharmacology and kinetic properties of the receptors were measured using electrophysiological analysis. Mutation of F124 had minimal effect on receptor pharmacology. However, the rate of deactivation was significantly increased compared to wild type. This study provides further information about the role of residues within a novel hydrophobic area of the GABA ρ1 receptor. This knowledge can help future studies into the design of potent and subtype-selective ligands with therapeutic value.
Publisher: Wiley
Date: 06-11-2023
DOI: 10.1111/BCP.15566
Abstract: Existing tacrolimus population pharmacokinetic models are unsuitable for guiding tacrolimus dosing in heart transplant recipients. This study aimed to develop and evaluate a population pharmacokinetic model for tacrolimus in heart transplant recipients that considers the tacrolimus‐azole antifungal interaction. Data from heart transplant recipients ( n = 87) administered the oral immediate‐release formulation of tacrolimus (Prograf®) were collected. Routine drug monitoring data, principally trough concentrations, were used for model building ( n = 1099). A published tacrolimus model was used to inform the estimation of K a , V 2 /F, Q/F and V 3 /F. The effect of concomitant azole antifungal use on tacrolimus CL/F was quantified. Fat‐free mass was implemented as a covariate on CL/F, V 2 /F, V 3 /F and Q/F on an allometry scale. Subsequently, stepwise covariate modelling was performed. Significant covariates influencing tacrolimus CL/F were included in the final model. Robustness of the final model was confirmed using prediction‐corrected visual predictive check (pcVPC). The final model was externally evaluated for prediction of tacrolimus concentrations of the fourth dosing occasion ( n = 87) from one to three prior dosing occasions. Concomitant azole antifungal therapy reduced tacrolimus CL/F by 80%. Haematocrit (∆OFV = −44, P .001) was included in the final model. The pcVPC of the final model displayed good model adequacy. One recent drug concentration is sufficient for the model to guide tacrolimus dosing. A population pharmacokinetic model that adequately describes tacrolimus pharmacokinetics in heart transplant recipients, considering the tacrolimus–azole antifungal interaction was developed. Prospective evaluation is required to assess its clinical utility to improve patient outcomes.
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1111/BCP.14357
Publisher: Springer Science and Business Media LLC
Date: 11-08-2020
Publisher: Springer Science and Business Media LLC
Date: 14-06-2021
Publisher: American Chemical Society (ACS)
Date: 15-06-2017
DOI: 10.1021/ACSCHEMNEURO.7B00105
Abstract: It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC
Publisher: Emerald
Date: 21-08-2019
DOI: 10.1108/JSTP-06-2018-0140
Abstract: The purpose of this paper is twofold: first, to test a hierarchical model with interrelationships between social support, value and brand equity to examine the effect of a transformative gamification service on users’ well-being behaviors and second, to demonstrate the usefulness of brand equity to measure social behavior brands encouraged via transformative gamification services. Data were collected ( n =351) via users of a transformative gamification service delivered via mobile in Iran. Structural equation modeling was used to test the model. The results revealed that the hierarchical model had a superior fit to the data over rival models measuring constructs at lower orders. The results also reveal that value mediates the relationship between social support and brand equity for social behavior. This is the first study to hierarchically test a model for transformative gamification services. Furthermore, it begins to shed light on the antecedents of value created within transformative gamification services, which to date have not been thoroughly explored. Finally, the study demonstrates brand equity is applicable beyond commercial c aigns and services and can be used to measure social (well-being) behaviors.
Publisher: Public Library of Science (PLoS)
Date: 19-07-2016
Publisher: American Chemical Society (ACS)
Date: 09-11-2018
DOI: 10.1021/ACSCHEMNEURO.7B00407
Abstract: Transporters in the SLC6 family play key roles in regulating neurotransmission and are the targets for a wide range of therapeutics. Important insights into the transport mechanisms and the specificity of drug interactions of SLC6 transporters have been obtained from the crystal structures of a bacterial homologue of the family, LeuT
Publisher: American Chemical Society (ACS)
Date: 07-02-2012
DOI: 10.1021/CN200121R
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.EJPHAR.2007.10.036
Abstract: The relative impact on picrotoxinin activity of residues at the intracellular (2' and 6' residues) and extracellular (15' and 17' residues) ends of the second transmembrane (M2) domain of the human gamma-aminobutyric acid-C (GABA(C)) rho1 receptor was investigated. A series of GABA(C) rho1 subunits were produced containing either single or multiple mutations at the positions of interest. Wild-type and mutant subunits (containing one or more of the following mutations: P2'S, T6'M, I15'N, G17'H) were expressed in Xenopus oocytes and characterized using agonists, partial agonists and antagonists. Changes in agonist activity were observed for mutant receptors. Most notably, mutation at the 2' position resulted in decreased agonist potency, while mutation at the 15' and 17' residues increased agonist potency. The affinity of the competitive antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) was unchanged compared to wild-type at all mutant receptors. Of the four residues studied, mutation of residues at the 2' and 6' positions had the greatest impact on picrotoxinin activity. Inclusion of the P2'S mutation typically produced receptors with increased picrotoxinin potency, while the T6'M mutation reduced picrotoxinin potency. Picrotoxinin is a mixed antagonist at wild-type and all mutant receptors, with the exception of the double mutant rho1P2'S/T6'M receptors at which the non-competitive component was isolated. It is proposed that the contribution of M2 domain residues to picrotoxinin activity is potentially two-fold: (1) their role as a potential picrotoxinin binding site within the pore and (2) they are critical for receptor activation properties of the receptor, thus may alter the allosteric mechanism of picrotoxinin.
Publisher: Elsevier BV
Date: 05-2004
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.NEUINT.2015.12.007
Abstract: Neurotransmitter transporters are targets for a wide range of therapeutically useful drugs. This is because they have the capacity to selectively manipulate the dynamics of neurotransmitter concentrations and thereby enhance or diminish signalling through particular brain pathways. High affinity glycine transporters (GlyTs) regulate extracellular concentrations of glycine and provide novel therapeutic targets for neurological disorders.
Publisher: Wiley
Date: 21-09-2021
DOI: 10.1111/BCP.14542
Publisher: Oxford University Press (OUP)
Date: 05-06-2018
Abstract: Chronic disease patients are adopting self-management techniques, such as using mobile health applications (apps). As GPs are the main caregivers of chronic disease patients, obtaining GP perspectives regarding patient use of mobile health apps is vital in understanding longer term value and feasibility of these apps. The aim was to determine GP perceptions of their current and potential roles in the use of health apps by their patients and how patient-focused apps affect patient management. Ten GPs participated in semi-structured, face-to-face interviews, which focused on their perceptions of, and involvement in, the use of patient-focused health apps. Interviews were transcribed verbatim and thematically analysed by two independent reviewers. GPs found that apps complemented their role in patient management as additional sources of medical information of their patients. They perceived that patient-focused apps would be part of their future practices however they noted that further work was required to incorporate them into their current practices. Currently, the main role of GPs was in promoting apps to patients. Suggestions for further engagement in mobile health included regularly reviewing patient data entered into health apps during consultations. GPs view patient-focused health apps positively, particularly to support them in providing patient care. Discussing information recorded in apps during consultations and frequent promotion of apps are feasible ways to integrate apps into their current work practices. Further studies involving evaluations of apps in improving health care delivery and patient communication in general practice are required.
Publisher: Oxford University Press
Date: 17-09-2009
Publisher: Elsevier BV
Date: 03-2007
Publisher: Springer Science and Business Media LLC
Date: 02-10-2020
DOI: 10.1186/S12910-020-00538-7
Abstract: Informed consent is often cited as the “cornerstone” of research ethics. Its intent is that participants enter research voluntarily, with an understanding of what their participation entails. Despite agreement on the necessity to obtain informed consent in research, opinions vary on the threshold of disclosure necessary and the best method to obtain consent. We aimed to investigate Australian researchers’ views on, and their experiences with, obtaining informed consent. Semi-structured interviews were conducted with 23 researchers from NSW institutions, working in various fields of research. Interviews were analysed and coded to identify themes. Researchers reported that consent involved information disclosure, understanding and a voluntary decision. They emphasised the variability of consent interactions, which were dependent on potential participants’ abilities and interests, study complexity and context. All researchers reported providing written information to potential participants, yet questioned the readability and utility of this information. The majority reported using signed consent forms to ‘operationalise’ consent and reported little awareness of, and lack of support in implementing more dynamic informed consent procedures, such as verbal informed consent, that was fit for the purposes of their studies. Views on Human Research Ethics Committees (HRECs) varied. Some reported inconsistent, arduous inputs on the information form and consent process. Others expressed reliance on HRECs for guidance, viewing them as institutional safeguards. This study highlights the importance of transparent relationships, both between researchers and participants, and between researchers and HRECs. Where the relationship with study participants was reported as more robust, researchers felt that they were better able to ensure participants made better, more informed decisions. Where the relationship with HRECs was reported as more robust, researchers were more likely to view them as institutional safeguards, rather than as bureaucratic hindrances. Conscientious and mindful researchers are paramount to ensuring the procedure accommodates in idual requirements. This study advocates that when designing ethical informed consent practices, researchers should be integrated as autonomous players with a positive input on the process, rather than, in the worst case, predatory recruiters to be curtailed by information forms and oversight.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2022
DOI: 10.1186/S12913-022-07927-1
Abstract: Few studies have explored the factors influencing user uptake of interventions designed to enhance therapeutic drug monitoring (TDM). This study aimed to identify barriers and facilitators to acceptance of a pilot intervention, the TDM Advisory Service (the Service), that provided prescribing advice for the antibiotic, vancomycin at an Australian public hospital. A s le of prescribers and pharmacists who had interacted with the Service ( n = 10), and a s le who had not ( n = 13), participated in semi-structured interviews. Interviews were transcribed verbatim and analysed independently by two researchers for emerging themes. The Theoretical Domains Framework (TDF) was used to synthesise barriers and facilitators to Service acceptance. Key barriers reported by participants who had interacted with the Service aligned with two TDF domains: ‘Social Influences’ (prescribing hierarchy) and ‘Environmental Context and Resources’ (accessibility of dose advice). For participants who had not interacted with the Service, key barriers aligned with two TDF domains: ‘Knowledge’ (uncertainty of Service processes) and ‘Environmental Context and Resources’ (accessibility of dose advice). Key facilitators for both participant groups aligned with ‘Beliefs about Consequences’ (improved prescribing and patient outcomes) and ‘Environmental Context and Resources’ (accessibility of dose advice). A novel domain, ‘Trust’, was identified. Independent of participant interaction with the Service, knowledge of Service processes, perceived beneficial outcomes, improved accessibility, and trust in Service capabilities were key determinants of acceptance. This evidence can be used to inform the adoption of strategies to adapt and enhance integration of the Service into clinical workflow.
Publisher: Wiley
Date: 12-02-2010
Start Date: 2015
End Date: 2018
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 2018
Funder: National Health and Medical Research Council
View Funded Activity