ORCID Profile
0000-0001-5496-935X
Current Organisation
University of South Australia
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Publisher: SAGE Publications
Date: 07-08-2023
DOI: 10.1177/10398562231191671
Abstract: This review aimed to identify current pharmacological and non-pharmacological treatment employed in emergency departments (EDs) for the management of patients presenting with illicit drug-related presentations (IDP) and compare current treatments with recommendations provided in guidelines. The review consists of English peer-reviewed journal articles and grey literature published in electronic databases: Ovid MEDLINE, PubMed, Embase Classic+Embase, Ovid Emcare and APA PsycInfo between 2015 and 2022. Twelve studies were identified from the search, with agitation and aggression being the most common presentations, and cannabis being the most prevalent illicit drug. Ventilatory support and restraints were the most reported non-pharmacological interventions while benzodiazepines and antipsychotics were the most commonly prescribed pharmacological agents. Non-coercive de-escalation strategies were recommended in all guidelines, with verbal de-escalation being the initial approach before other interventions, such as medications and restraints. However, de-escalation strategies were not reported in any studies. Pharmacological interventions for patients with IDP and related symptoms were in accordance with guidelines. Use of restraints was identified in included studies with notable lack of reporting of de-escalation strategies which may have been deemed insignificant and not reported. Future research could investigate the appropriateness of restrictive interventions as well as the employment of non-restrictive de-escalation strategies.
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/PY18047
Abstract: Patients obtaining a prescription from a pharmacy expect that the drug will be effective and have minimal side-effects. Unfortunately, drugs exhibit the desired effect in ~25–60% of people prescribed any medication. Adverse effects occur at a rate of 10% in patients taking a medication, and this rate increases during and after hospitalisation, with the transition of care back to the ambulatory setting posing a particular risk. Pharmacogenomics testing has been shown to optimise pharmacotherapy by increasing medication effectiveness and reducing drug-related toxicity, thus curtailing overall healthcare costs. Evidence from international studies have shown that community pharmacists would be able to offer this highly relevant professional service to their clients, given suitable training. This specific training complements pharmacists’ existing skills and expertise by educating them in an emerging scientific area of pharmacogenomics. However, in an increasingly tight financial climate, the provision of pharmacogenomics testing by Australian community pharmacists will only be viable with an appropriate reimbursement through the Medicare Benefits Schedule, currently accessible by other allied health practitioners but not by pharmacists.
Publisher: Public Library of Science (PLoS)
Date: 07-11-2013
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Publisher: SAGE Publications
Date: 07-11-2022
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.JNEUROIM.2005.04.003
Abstract: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. The cytotoxic T lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analysed the CTLA4 +49A/G and CT60 polymorphisms in a cohort of 120 MS trio families recruited from the Flanders region in Belgium. Both polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The +49 G-allele was significantly more transmitted to affected probands (P = 0.005). No transmission distortion was observed for the CT60 polymorphism. Haplotype analysis revealed significant overtransmission of the +49 A/G*G-CT60*G haplotype (P = 0.0025), and undertransmission of the +49 A/G*A-CT60*G haplotype (P = 0.015). The CTLA4 gene has been the focus of intense investigation in MS. Of 15 recently published papers, only six reported significant associations of various CTLA4 polymorphisms with MS, with the remainder being negative. Ours is the first report investigating the CT60 polymorphism in MS. Our data highlight a need for further scrutiny of the CTLA4 gene in MS.
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.YEXMP.2005.09.004
Abstract: Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2% P=0.02 OR=1.28 95% C.I.=1.04-1.58) and JIA (61.8% P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.
Publisher: SAGE Publications
Date: 17-09-2013
Abstract: Common IFN lambda 3 ( IFNL3) variants have been demonstrated to affect spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. The functional basis of these genetic variants has yet to be determined. Data examining the effect of IFNL3, specifically, in innate immune cells is lacking. Here, we determined the expression of IFNL3 and its receptor IFNLR1 in blood immune cell subsets and in HCV-infected livers. Next we assessed their sensitivity to IFNL3. All participants were genotyped for the IFNL3 SNPs rs8099917 and rs12979860. Importantly, unstimulated blood immune cells express significantly higher levels of IFNL3 than HCV liver biopsies. Plasmacytoid dendritic cells (pDCs) are the predominant producers of IFNLR1, especially in response to IFN-α. PBMCs, monocytes and pDCs all respond to IFNL3 based on MxA up-regulation. No differences in IFNL3 expression levels between rs8099917 or rs12979860 genotypes were detected. This is the first study to show peripheral blood pDCs to be the main producers of IFNL3, especially compared with HCV-infected livers. This makes innate immune cells the key players in determining the functional significance of INFL3 polymorphisms in patients with HCV.
Publisher: Wiley
Date: 26-10-2005
Publisher: Springer Science and Business Media LLC
Date: 18-04-2013
DOI: 10.1038/GENE.2013.15
Abstract: IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 (CCR5) gene (CCR5-Δ32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Δ32 in treatment-induced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-α and ribavirin (RBV) was genotyped for the CCR5-Δ32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Δ32 did not influence treatment-induced recovery to IFN-α/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Δ32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, P<0.0001), but not in Australians of European ancestry. In conclusion, CCR5-Δ32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Δ32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.
Publisher: Oxford University Press (OUP)
Date: 04-09-2021
Abstract: This study aimed to explore the range of activities provided by community pharmacists for promoting mental well-being in Australia. An online survey was developed and piloted by 2 community pharmacists, 1 representative from the Pharmaceutical Society of Australia and 11 pharmacy students for content and face validity. Community pharmacists were recruited via direct emails to pharmacy groups and social media between November 2019 and January 2020. Descriptive statistics and chi-squared analyses were conducted. Data were analysed from 85 pharmacists (of 115 total pharmacy staff respondents). Although 40% reported working in a pharmacy that promoted mental well-being, most (88.2%) were not involved in such activities. However, most respondents (88.0%) identified community pharmacy as a suitable setting to promote mental well-being. Barriers to mental well-being promotion included busy pharmacy environment with competing priorities, a lack of staff training and confidence in discussing mental well-being and stigma associated with mental illness. Community pharmacy presents a suitable setting to promote mental well-being. However, pharmacists may not be utilizing their full range of skills and knowledge in promoting a national health priority. This study identified opportunities for increased pharmacist-led promotion of mental well-being, particularly given the emerging mental health impacts of the COVID-19 pandemic. The pandemic has highlighted the growing urgency for mental health-friendly health workers across the sector including the community pharmacy workforce to engage consumers about their mental well-being.
Publisher: Springer Science and Business Media LLC
Date: 2011
DOI: 10.1186/GM273
Publisher: Oxford University Press (OUP)
Date: 29-06-2018
DOI: 10.1111/IJPP.12466
Abstract: To identify patterns of medication load, client’s care team, coordination of healthcare and clients’ understanding of their medications. Face-to-face interviews were conducted with community-dwelling older Australians between June and August 2017 in three community pharmacies in Adelaide, South Australia. Forty interviews were conducted. On average, participants were taking 7.53 medicines with 77.5% using five or more regularly. Lack of collaboration between healthcare professionals, need for increased communication between prescribers and increased patient education on medicines, were highlighted. This study demonstrates that polypharmacy and inappropriate prescribing are occurring within the community pharmacy setting, but shows insight into how these concerns can be overcome, by implementing pharmacist-led services such as non-dispensing pharmacists in community pharmacies. Careful consideration when prescribing and effective communication are required to minimise risks associated with polypharmacy in this population.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2020
Publisher: Oxford University Press (OUP)
Date: 30-01-2021
DOI: 10.1093/IJPP/RIAA020
Abstract: The nation was recovering from the aftermath of the catastrophic 2019–2020 bushfires when the first cases of the COVID-19 pandemic emerged in Australia. During the peak of the pandemic, Australia closed both its state and international borders to all travelers and interstate travel was very tightly regulated. Community pharmacists and pharmacy staff were one of the very few primary healthcare workers still serving their communities during these periods of strict lockdown. In this personal view article, the challenges and their toll on the mental health and wellbeing of these “essential workers” are described. Community pharmacists and pharmacy staff were under immense pressure to remain open and serve their communities amidst rapidly changing legislation and, at times, conflicting advice from the range of Australian health agencies. Rapid changes to workload and workflow were combined with the dilemma of balancing professional obligations with the personal duty of keeping themselves and their sometimes geographically distant families safe. Fluctuating demands and traumatic situations found community pharmacy staff often feeling distressed and underprepared. Despite a global pandemic following a season of extraordinary bushfires, it has barely been acknowledged that community pharmacy staff are one of the highest risk groups for long-term psychological impacts. To our knowledge, very little research has addressed the toll of these cataclysmic events on this group of essential healthcare workers.
Publisher: Hindawi Limited
Date: 23-09-2022
DOI: 10.1111/HSC.14029
Abstract: In Australia, mental illness has been recognised as a National Health Priority area, with the coronavirus pandemic adding a layer of urgency to the need to address the multiple health problems faced by clients with mental illnesses. Whilst much has been done in efforts to support these clients, little is known about their medication knowledge and experience with health professionals. The aim of the study was to explore the knowledge and beliefs of clients on the use of psychotropic medications and study their experiences with healthcare providers. Adult participants at a not-for-profit community-managed specialist mental health service provider in Adelaide, South Australia were recruited. Four focus group sessions were conducted between February 2020 and March 2021. All sessions were co-facilitated by a peer practitioner with lived experience. Sessions were audio recorded and transcribed verbatim. Participants (n = 27) reported that provision of medication education was inadequate and, in some cases, non-existent. There was an apparent lack of support for monitoring and managing common side effects, such as weight gain. Participants described not being involved in any decision-making processes and that establishing and maintaining a therapeutic relationship with their healthcare providers was challenging. Perceived stigma remains a barrier in accessing healthcare. Despite participants regularly interacting with a range of healthcare providers, findings highlight key gaps in care, particularly medication education and establishing a therapeutic relationship with their healthcare providers. Future mental health reforms should consider the provision of additional medication education in community settings, such as at not-for-profit organisations. Moreover, healthcare providers should take a proactive approach in establishing therapeutic relationships.
Publisher: Oxford University Press (OUP)
Date: 16-02-2023
DOI: 10.1093/IJPP/RIAD014
Abstract: During the COVID-19 pandemic, Australian community pharmacists delivered a wide range of professional services, including COVID-19 vaccinations. The aim of this study was to understand the reasons for and attitudes of consumers receiving COVID-19 vaccinations from community pharmacists. A nationwide anonymous online survey recruited consumers above the age of 18 years who had received their COVID-19 vaccinations at community pharmacies between September 2021 and April 2022. COVID-19 vaccinations at community pharmacies were positively received by consumers due to their convenience and accessibility. Future health strategies should utilise the highly trained workforce of community pharmacists for wider public outreach.
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJOPEN-2021-059573
Abstract: Physical health conditions are the leading causes of death in people living with severe mental illness. In particular, the risk of metabolic syndrome the constellation of abnormalities in weight, blood pressure, blood glucose and lipid levels, is high in this cohort. It has been recognised that commonly prescribed pharmacological agents for mental illness can further lify the risk of developing metabolic syndrome therefore, monitoring guidelines are in place for consumers prescribed antipsychotics. However, there is a disconnect between recommended guidelines and current practice. Our study aims to investigate: (1) the feasibility of a community pharmacist-led physical health monitoring for metabolic parameters in consumers with mental illness currently taking second generation antipsychotics and (2) the potential outcomes of the intervention (eg, rates and outcome of referrals to general practitioners, relationship between the pharmacist’s lifestyle counselling advice and change in metabolic parameters). We propose a longitudinal metabolic monitoring study led by community pharmacists with one-to-one consultations between trained pharmacists and participants at set intervals over a 12-month period. Our primary outcome is to determine the feasibility of the pharmacist-led intervention. The secondary outcome is to explore the overall health outcomes of consumers enrolled in the intervention. This is a mixed-methods study including both quantitative and qualitative outcomes. Qualitative data will be analysed via the process of data immersion, coding and identification of themes. Quantitative outcomes will be analysed using IBM Statistics SPSS software. Univariate descriptive, regression analysis and dependent t-tests will be performed. Statistical significance will be at α 0.05. Our study has been approved by the institutional Human Research Ethics Committee (Protocol no: 203433). Findings will be made publicly available in peer-reviewed articles, conference presentations to health professionals, as well as other stakeholders. Protocol V.2.1, August 2021. ACTRN12621001435875.
Publisher: Public Library of Science (PLoS)
Date: 04-02-2022
DOI: 10.1371/JOURNAL.PONE.0263284
Abstract: Heart failure (HF) is an increasing global concern. Despite evidence-based pharmacotherapy, morbidity and mortality remain high in HF. Medication non-adherence is a crucial factor in optimising clinical outcomes. A growing number of smartphone applications (apps) assist management. While evidence support their use to promote treatment adherence, apps alone may not be the solution. The objective of this pilot study is to assess the acceptability and feasibility of a tiered intervention added to the NPS MedicineWise dose reminder app (MedicineWise app) in supporting medication adherence in HF. This prospective, single-blinded, randomised controlled trial will recruit 55 Australian patients with HF to be randomly assigned to either intervention (MedicineWise app + usual care) or control (usual care alone) arm. Control participants will remain unaware of the intervention throughout the study. At baseline, intervention participants will be instructed in the MedicineWise app. A reminder will then prompt medication administration at each dosing interval. If non-adherence is suggested from 24 hourly reports (critical medications) or 72 hours (non-critical medications), the in idual/s will be escalated through a tiered, pharmacist-led intervention. The primary outcome will be the acceptability and feasibility of this approach in supporting adherence. Between-group comparison of the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) at baseline, 3 and 6 months will be used to measure the app’s value in supporting adherence. Secondary outcome measures include self-reported medication adherence and knowledge, health-related quality of life, psychological wellbeing, signs and symptoms of HF, and medication and HF knowledge. The protocol received ethics approval from Central Adelaide Clinical Human Research Ethics Committee (Protocol number R20190302) and University of South Australia Human Research Ethics Committee (Protocol number 202450). Findings will be disseminated through peer-reviewed journals. Australian New Zealand Clinical Trials Registry Clinical trial number: ACTRN12619000289112p ( www.ANZCTR.org.au/ACTRN12619000289112p.aspx )
Publisher: Springer Science and Business Media LLC
Date: 13-09-2009
DOI: 10.1038/NG.447
Abstract: Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian in iduals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 in iduals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3 rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.
Publisher: FapUNIFESP (SciELO)
Date: 03-2007
DOI: 10.1590/S0004-282X2007000100005
Abstract: This study aimed to investigate in a population of Brazilian patients with multiple sclerosis (MS) single-nucleotide polymorphisms (SNP) in the promoter region of IL4 (*33C-T) and receptor IL4R (*Q551R A-G) genes proposed to interfere with disease progression. No significant differences were observed in either of the SNPs investigated between healthy controls (n=135) and MS patients (n=129). However, the IL4+33 TT genotype was significantly (p=0.039) higher in African descendants MS (AF-MS= 9.09%) than in Caucasian MS (CA-MS= 1.35%). It was also observed a significant (p=0.016) increase for the IL4R* Q551R CC genotype in AF-MS compared to those of Caucasian ethnicity (AF-MS= 21.62% CA-MS= 4.35%). These results suggest that IL4+33 and IL4R*Q551 polymorphisms may have a disease-promoting role of TH2 mediators in African MS descendants. Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.
Publisher: MDPI AG
Date: 18-11-2022
DOI: 10.3390/JPM12111927
Abstract: In advanced cancer, pain is a poor prognostic factor, significantly impacting patients’ quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-in idual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.JNEUROIM.2007.04.017
Abstract: Four CTLA4 polymorphisms were investigated in a Northern Irish collection of relapsing-remitting (RR) and primary-progressive (PP) multiple sclerosis (MS) patients. The CTLA4 promoter (-318 C/T), exon 1 (+49 A/G) and intergenic CT60 SNPs, as well as a microsatellite found in the 3' UTR (AT(n)) were analysed in 246 RRMS, 84 PPMS and 158 healthy controls. The A allele of the exon 1 +49 A/G SNP (OR=1.36 95% CI=1.11-1.81 P=0.038), and more so the AA genotype (OR=1.70 95% CI=1.11-2.60 P=0.015) were associated with RR, but not PPMS. In the PPMS population, overall allele distribution of the AT(n) microsatellite was significantly different from that in the healthy controls. We did not find any association with the promoter (-318 C/T) or intergenic CT60 SNPs in either of the disease cohorts. In concordance with several recent studies, we detected a trend toward higher carriage rates of the +49 G allele in PP vs RR MS patients (66.7% vs 58.9%), though this was not significant. Our data highlight the CTLA4 +49 A/G and 3'UTR polymorphisms as potential modifiers of disease course in MS.
Publisher: Informa UK Limited
Date: 09-06-2014
DOI: 10.1517/17425255.2014.925880
Abstract: A number of disease-modifying therapies have become available to treat multiple sclerosis (MS) in recent years. As the effects of these medications are unpredictable and they are generally used for a number of years, the selection of the most appropriate disease-modifying agent must be based on the long-term efficacy and toxicity profile, thus strategies to personalise treatment to optimise responses may be potentially very useful. This review provides an overview of the efficacy and toxicity of disease-modifying agents used in MS and specifically discusses any metabolic side effects and advances in personalising the use of each of these agents. Medline and EMBASE were searched for any articles regarding the efficacy, toxicity and personalised use of the medicines discussed in this review. Disease-modifying agents used to treat MS differ substantially in their efficacy and toxicity profile, but metabolic side effects appear to be limited to alemtuzumab, teriflunomide and IFN-β. Although personalised treatment strategies to assist in selection of the most appropriate disease-modifying agent for MS are limited, there is substantial potential to use genetic sub-studies of the many recent trials investigating disease-modifying agents to develop personalised treatment strategies.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.YEXMP.2006.02.001
Abstract: Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the in idual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02 OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001 OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.AUTREV.2013.10.012
Abstract: Multiple sclerosis (MS) is one of the most common inflammatory and degenerative autoimmune diseases of the central nervous system with considerable heterogeneity in all aspects, including response to therapy. A number of disease modifying drugs, including traditional first line agents such as, interferon-beta (IFN-β) and glatiramer acetate (GA) are available for disease management. However, a considerable number of patients fail to achieve adequate response at therapeutic doses of IFN-β or GA. This variability in response to treatment has prompted the search for prognostic markers in order to personalize and optimize therapy so as to treat MS more efficiently. This review will summarize the existing literature examining the pharmacogenomics of IFN-β and GA response in MS patients.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2015
DOI: 10.1038/NCOMMS7422
Abstract: Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism ( rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates ( P .0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.
Publisher: Public Library of Science (PLoS)
Date: 13-09-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2012
DOI: 10.1002/HEP.25582
Abstract: In patients with chronic hepatitis C virus (HCV) infection, several variants of the interleukin-28B (IL28B) gene have been shown to correlate significantly with a sustained virologic response (SVR). Recent evidence shows that determination of one single IL28B polymorphism, rs12979860, is sufficient for predicting treatment outcome. We examined whether the combined determination of the IL28B single-nucleotide polymorphisms (SNPs), rs12979860, rs8099917, rs12980275, and rs8103142, might improve the prediction of SVR in patients with HCV. In the study cohort, 54% of 942 patients with chronic HCV type 1 infection had SVR. The IL28B SNPs, rs12979860CC and rs8099917TT, correlated significantly with SVR (68% and 62%). The SNPs, rs12980275 and rs8103142, were in strong linkage disequilibrium with rs12979860 and were not included in further analysis. In homozygous carriers of the rs12979860 responder allele C, additional genotyping of the rs8099917 SNP had no effect on response prediction, whereas in carriers of the rs12979860 nonresponder allele, the rs8099917 SNP improved the response prediction. In heterozygous carriers of the rs12979860 nonresponder T allele, SVR rates were 55% in the presence of the rs8099917TT genotype and 40% in patients carrying the rs8099917 TG or GG genotype. Analysis of an independent confirmation cohort of 377 HCV type 1-infected patients verified the significant difference in SVR rates between the combined genotypes, rs12979860CT/rs8099917TT and rs12979860CT/rs8099917TG (38% versus 21% P = 0.018). Treatment outcome prediction could not be improved in homozygous carriers of the IL28B rs12979860 C responder allele by the additional determination of the rs8099917 SNP. There is evidence that a significant proportion of heterozygous carriers of the rs12979860 T nonresponder allele can profit with respect to SVR prediction by further determination of the rs8099917 SNP. (HEPATOLOGY 2012 :1700-1710).
Publisher: MDPI AG
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 16-01-2014
DOI: 10.1038/GENE.2013.66
Abstract: The IFNL3 genotype predicts the clearance of hepatitis C virus (HCV), spontaneously and with interferon (IFN)-based therapy. The responder genotype is associated with lower expression of interferon stimulated genes (ISGs) in liver biopsies from chronic hepatitis C patients. However, ISGs represent many interacting molecular pathways, and we hypothesised that the IFNL3 genotype may produce a characteristic pattern of ISG expression explaining the effect of genotype on viral clearance. For the first time, we identified an association between a cluster of ISGs, the metallothioneins (MTs) and IFNL3 genotype. Importantly, MTs were significantly upregulated (in contrast to most other ISGs) in HCV-infected liver biopsies of rs8099917 responders. An association between lower fibrosis scores and higher MT levels was demonstrated underlying clinical relevance of this association. As expected, overall ISGs were significantly downregulated in biopsies from subjects with the IFNL3 rs8099917 responder genotype (P=2.38 × 10(-7)). Peripheral blood analysis revealed paradoxical and not previously described findings with upregulation of ISGs seen in the responder genotype (P=1.00 × 10(-4)). The higher MT expression in responders may contribute to their improved viral clearance and MT-inducing agents may be useful adjuncts to therapy for HCV. Upregulation of immune cell ISGs in responders may also contribute to the IFNL3 genotype effect.
Publisher: Hindawi Limited
Date: 08-07-2014
DOI: 10.1111/JCPT.12189
Abstract: A common polymorphism (C1858T) in the gene that encodes the protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with altered T-cell responses and increased susceptibility to rheumatoid arthritis (RA) and other autoimmune diseases. Teriflunomide, the active metabolite of leflunomide, reduces T-cell responses through inhibition of tyrosine kinase p56LCK. We examined a potential association between PTPN22 genotype and response or toxicity to leflunomide in Caucasian RA patients taking leflunomide in combination with other disease-modifying antirheumatic drugs (DMARDs). Patients enrolled in the Royal Adelaide Hospital RA inception cohort and taking leflunomide were eligible for inclusion. Participants were followed for 12 months after leflunomide initiation or until either another DMARD was added or leflunomide was ceased. Clinical response according to change in 28-joint Disease Activity Score (DAS28) and cessation due to toxicity were assessed. A total of 94 participants were included in the study, 75 of whom carried the CC genotype, 18 the CT, whereas one in idual carried the TT genotype. Over the first 12 months of leflunomide treatment, there was no statistically significant relationship between carrying the T allele and change in DAS28 (-0·84 vs. -1·15, P = 0·446) nor with cessation of leflunomide treatment due to side effects (P = 0·433). These results indicate that PTPN22 C1858T genotype has no effect on response or toxicity outcomes in leflunomide-treated RA patients. This is the first study to evaluate the biologically plausible hypothesis that PTPN22 genotype might be a predictor of response/toxicity to leflunomide therapy. Despite this, PTPN22 genotype was not associated with leflunomide response or toxicity in patients with RA.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2013
DOI: 10.1038/TPJ.2013.43
Abstract: In the current study, we have used the haplotype-tagging single-nucleotide polymorphisms (SNPs) to determine associations between genetic variants in SCN1A and treatment response in 519 Caucasian patients with known response status for epilepsy treated with antiepileptic drugs (AEDs) with sodium channel blocking effects. Nine SNPs within SCN1A were genotyped in this cohort. The only association observed was for rs10188577. A greater proportion of drug-resistant patients were heterozygous compared with drug responsive patients (48.3% vs 35.4%, P=0.014). After correction for potential confounding factors, the association for rs10188577 was only marginally significant (P=0.049). In light of our findings, it seems unlikely that rs10188577 could be a major determinant of response to AEDs. However, looking at the influence of rs10188577 on the expressed quantitative trait association patterns within the immediate vicinity of SCN1A, we found significant associations with neighbouring sodium channel genes, SCN7A and SCN9A (P<0.025), which warrants further studies.
Publisher: Future Medicine Ltd
Date: 06-2021
Abstract: Although statins are effective in treating high cholesterol, adverse effects do occur with their use. Efficacy and tolerability vary among statins in different ethnic groups. Indigenous Australians have a high risk for cardiovascular and kidney diseases. Prescribing statins to Indigenous Australians with multi-morbidity requires different strategies to increase efficacy and reduce their toxicity. Previous studies have reported that Indigenous Australians are more susceptible to severe statin-induced myopathies. However, there is a lack of evidence in the underlying genetic factors in this population. This review aims to identify: inter-ethnic differences in the efficacy and safety of statins major contributing factors accounting for any identified differences and provide an overview of statin-induced adverse effects in Indigenous Australians.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2020
DOI: 10.1038/S41598-020-66991-X
Abstract: Potentially inappropriate medications (PIMs) can contribute to morbidity through exacerbations or progression of existing conditions among older people. In order to characterize the prevalence of PIMs according to the Beers Criteria in older Australians, three hundred and eleven participants were recruited from three residential aged care facilities (RACFs) and two hundred and twenty participants from three community pharmacies in South Australia for a retrospective audit of medication administration charts and community pharmacy dispensing histories. Although a similar number of participants were prescribed at least one PIM (P = 0.09), the average number of PIMs was significantly greater in the RACF cohort (1.96 vs 1.26, P 0.05). Additionally, PIMs prescribed as pro re nata (PRN) in the RACF cohort had a significantly low administration rate compared to prescription rate (19.7% vs 40.7%). The mean number of PIMs within each cohort was statistically significant (RACF = 1.93 vs CDOA = 1.26, P 0.05). RACF residents were at a slightly greater risk of being prescribed more than one PIM compared to those within the community. Routine medication reviews by pharmacists embedded in RACFs and within the community could be utilised to detect PIMs before such harm occurs.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2014
DOI: 10.1038/TPJ.2013.45
Abstract: Sulphasalazine (SSA) is a disease modifying anti-rheumatic drug (DMARD) that is commonly used to treat rheumatoid arthritis (RA). Plasma levels of SSA and its metabolite sulphapyridine are influenced by common polymorphisms in genes that encode N-acetyl transferase 2 (NAT2) and ATP-binding cassette protein G2 (ABCG2). Study participants had early RA that was treated with a combination DMARD regimen that included SSA. Toxicity was defined by cessation of SSA due to adverse effects and response as remission after 12 months of treatment. The effect of variables on toxicity was assessed by a Cox-proportional Hazard model and response by logistic regression. After correction for conventional variables, toxicity in 229 participants was influenced by NAT2 phenotype (hazard ratio=1.74 (95% confidence interval (CI) 1.01-3.21), P=0.044) and remission in 141 participants was associated with ABCG2 genotype (odds ratio=3.34 (95% CI 1.18-9.50), P=0.024). In our s le of early RA patients who were primarily treated with a combination of DMARDs, common variants in genes that encode NAT2 and ABCG2 were associated respectively with toxicity and response to SSA.
Publisher: Elsevier BV
Date: 12-2014
No related grants have been discovered for Vijay Suppiah.