Professor Jennifer Martin
Chair of Clinical Pharmacology
School of Medicine and Public Health
- Email:jen.martin@newcastle.edu.au
- Phone:(02) 4042 0851
Translating research into practice and policy
Optimising choice, dose and timing of medicines for a particular patient are the focus of Professor Jennifer Martin's clinical work and research career.
Professor Jennifer Martin is the Chair of the discipline of Clinical Pharmacology in the School of Medicine and Public Health at the University of Newcastle.
Working in the Hunter New England Local Health District, Jennifer leads a team of pharmacy and medicine experts together with pharmacoepidemiologists and pharmacoeconomists, who work across a number of areas including cancer.
Most often centering on therapeutic drugs, the team look at everything from the design and development of drugs, to the clinical trials process, through to the post-marketing phase, where data is collected on how effective those drugs are in practice, and any side effects they might have.
MEDICAL CANNABIS TRIALS
In July 2015, the NSW government announced Australia's first medical cannabis trial for terminally ill adult cancer patients. The Hunter will serve as a recruitment hub for this study and the UON clinical pharmacology group will lead the dose-finding study in the Hunter, together with UON's Conjoint Professors Stephen Ackland and Katherine Clark.
Although likely to polarise opinion, the study could significantly improve the well being of terminal patients at the end of life.
To be conducted in two phases, the trial will assess the ability of cannabis to relieve symptoms including fatigue, low appetite, altered taste and smell for food, low mood, weight loss, nausea, insomnia and pain relief.
Jennifer believes the team was chosen to run the pharmacology aspects of the cannabis trial due to the long history of excellence in the UON Clinical Pharmacology department (previous Chairs include Emeritus Professor Tony Smith and Professor David Henry), and the high level of analytical support offered by the University of Newcastle, led by Dr Peter Galettis.
In line with her focus on optimising the therapeutic benefits of medication, Jennifer sees this trial as a vital opportunity to assess and quantify a drug already being used by many extremely ill patients.
The first phase of the trial will produce world-class pharmacokinetic analysis and sophisticated modelling to inform drug dosage and frequency of administration.
CHALLENGING CONFOUNDERS
Jennifer dismisses the notion expressed by certain quarters of the community that this trial has more to do with political agenda than patient quality of life.
"At the end of the day, we want our patients to access this drug if it proves effective."
"Identifying exactly what helps, how it helps, how much a patient needs and possible side effects is vital," she says, "especially if those side effects are worse than the symptoms being treated."
The team is sourcing pharmaceutical grade cannabis from commercial suppliers overseas who complete rigorous testing, which rule out contaminants such as mould, and authenticate uniform potency.
To further ensure consistency throughout the trial, vaporisers have been chosen as a method of delivery.
"We know that when you eat cannabis in food, there is a huge variability between the amount that you eat and how much you actually need to feel good," Jennifer explains.
"This depends on what meal you have eaten, other drugs you have taken and how well you are."
"But if you inhale it, it goes straight through the lining of your nose or mouth into the bloodstream," she continues.
"If we can be sure the equipment and potency of the cannabis are uniform, we don't have any confounders muddying our understanding of the relationship between dose and effect in a particular person."
THE ROAD TO RHODES
Jennifer spent her childhood in Wellington, New Zealand, where her initial interest in medicine grew from a love of sport. She decided early on that she would become the doctor who travelled with the New Zealand Olympic team.
While studying at the University of Otago, changes to tertiary funding forced medical students to take out large loans, with interest accruing during their student years. Upon graduating, many began work as doctors in New Zealand, but then moved to the United Kingdom or Australia, to pay off their increasing debt.
"By that stage, my eyes were opened to the issues of unequal access to tertiary education, health care and user pays," she recalls.
In 1993, keen to further understand the consequences of inequity in healthcare access, Jennifer was awarded a prestigious Rhodes Scholarship to study politics, philosophy, and economics at the University of Oxford.
Returning to New Zealand, Jennifer trained as a specialist in pharmacology and internal medicine.
"I like that pharmacology is the study of drugs across all areas."
"You get very broad training, but it is also closely related to those wider issues of access to health care resources and drugs," explains Jennifer.
In 2000, Jennifer went to Melbourne to undertake her PhD from Monash University, examining innate immunity in Type 2 diabetes. Subsequent postdoctoral work at the Walter and Eliza Hall Institute focused on the function of macrophages with high fat diet. A stint at the University of Queensland as Head of the Southside Clinical School followed. Here, Jennifer became involved in medical curricula as a method of broadening the experiences and understanding doctors have about medicine and healthcare.
The opportunity to apply for the Chair of Clinical Pharmacology at the University of Newcastle combined with encouragement from leaders in the field to do so, convinced Jennifer to pursue the clinical pharmacology leadership position in 2013.
TEAM COACH
Jennifer is quick to point out that the entire Pharmacology team is working toward the improvement of patients' lives, not just on the cannabis trial, but on a range of research and community leadership roles in medicines' use.
She sees herself not as someone who must actively manage the work of those she leads, but more of a coach helping her team to reach their goals.
"We have a general understanding that people in this group contribute to clinical and medicines research and service."
"They are in charge of pursuing their own research agenda but we need to provide support and opportunities for that," she explains.
Postgraduate students under Jennifer's supervision are developing a mass spectroscopy library and clinical validation for synthetic drugs of abuse, and developing programs to optimise dose and timing of cancer therapies.
Future research will continue to focus on drug individualisation using drug phenotype data, and developing evidence around biosimilars.
Members of Jennifer's team also have a focus on generating evidence to guide the deprescribing of medications - particularly in people with a lot of comorbidity or at the end of life.
MOTIVATED TO RIGHT WRONGS
An intuitive and award winning teacher, Jennifer's style in the classroom is somewhat unconventional.
"My classes are very interactive because I want the students to think," she says.
"We do everything on the whiteboard so they have to interact."
She laughs as she reflects on her propensity to be diverted by tangents in class, but solemnly states her belief that teaching well involves admitting to past errors to prevent students from repeating them.
"I think one of the most important functions of being a professor is mentoring and training the next generation. I think it is a shame that the university system rewards you so well for research but not for teaching."
Not that Jennifer could ever be accused of lagging in research, or any other aspect of her career.
The practicing physician, teacher, researcher, multiple committee and editorial board member, and mother of four wants you to know she is not as intimidating as she looks on paper.
"I am very aware of the impression I make when I say things like 'I was a Rhodes Scholar'," she reflects.
"I just applied for the scholarship, had a vision of what I wanted to do and I got it. So I don't think of it as any badge of achievement, it was just what I did."
"The experience has cemented a responsibility to do something helpful for the community," Jennifer adds.
"I am motivated, but my motivation is to try and ensure equity of access to opportunities based on merit in a society of entitlement, where some people get preferential treatment."
"I know I can't override thousands of years worth of inequity, but I'm doing it in my own small way and I hope that it eventually has some benefit in terms of access to medicines."
Translating research into practice and policy
Optimising choice, dose and timing of medicines for a particular patient are the focus of Professor Jennifer Martin's clinical work and research career.
Career Summary
Biography
Professor Martin is a dual trained clinical pharmacologist and practising general physician. She has studied politics and health economics at Oxford University as a Rhodes Scholar and has used this experience to serve on the Pharmaceutical Benefits Advisory Committee, the Economic Subcommittee of the PBAC and other Government and Statewide committees examining appropriate allocation, regulation, safety and efficacy in pharmaceuticals. She is a Member of the Australian Institute of Company Directors (Diploma).
Her PhD (Monash) examined innate immunity in Type 2 diabetes and subsequent postdoctoral work at the Walter and Eliza Hall focussed on the function of macrophages with high fat diet. Her recent research is in the area of clinical development of both novel and old drugs for a variety of diseases and has developed a collaboration with Leiden University using clinical pharmacological methods generally to improve dosing, with EKUT (Germany) in the combined role of therapeutic drug monitoring (TDM) and pharmacogenetics to individualise choice and dose of chemotherapy, and with the National Institutes of Health in identifying and managing synthetic drugs of abuse.
Her current PhD students are researching cannabinoid therapies, targeted cancer therapies, dosing in neonates and therapeutic drug monitoring in clinical care including with antimicrobial therapies. Professor Martin is passionate about teaching in the area of clinical pharmacology and been involved in curriculum development for medical students (Otago, Monash, Queensland and Melbourne Universities) was the recent teaching and learning representative on the STC in clinical pharmacology for the College of Physicians (RACP). She is currently a member of the RACP Policy and Advocacy Committee, the Council of the Australasian Society for Clinical and Experimental Pharmacology and Therapeutics, and a member of the Pharmacology and Therapeutics Advisory Committee of PHARMAC, the sole purchaser for pharmaceuticals in New Zealand.
Research ExpertiseProfessor Jennifer Martin is Chair of Clinical Pharmacology in the School of Medicine and Public Health at the University of Newcastle and a practicing general physician for the Hunter New England Local Health District. She is also the Director of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), a National Health and Medical Research Council (NHMRC) Centre of Research Excellence.
Qualifications
- PhD, Monash University
- Bachelor of Medicine & Surgery, University of Otago - New Zealand
- Master of Arts, University of Oxford - UK
Keywords
- Clinical pharmacology
- Personalized medicine
- Pharmaceutical pricing and regulation
- Targeted therapies
Fields of Research
Code | Description | Percentage |
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321402 | Clinical pharmacology and therapeutics | 100 |
Professional Experience
Academic appointment
Dates | Title | Organisation / Department |
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1/9/2015 - | Head, Discipline of Medicine, University of Newcastle | School of Medicine & Public Health, Faculty of Health & Medicine, University of Newcastle | Australia Australia |
1/8/2015 - | Chair of Clinical Pharmacology | University of Newcastle - Faculty of Health and Medicine, School of Medicine and Public Health School of Medicine and Public Health Australia |
1/1/2013 - | Membership | National Prescribing Service Executive – RADAR Australia |
1/1/2013 - | Membership | Diamantina Health Partners Symposium Organising Committee Australia |
1/1/2013 - | Membership | IATDMCT Oncology Committee Australia |
1/1/2012 - | Membership | Diamantina Health Partners Evidence and Innovation Theme Australia |
1/1/2012 - | Membership | Diamantina Health Partners Neuroscience and Recovery Centre Steering Committee Australia |
1/1/2011 - | Editorial Board | Journal Clinical Toxicology Australia |
1/1/2011 - | Membership | IATDMCT Standard Laboratory Practices (SLP) committee Australia |
1/1/2011 - | Membership | Queensland Health Improving Presribing Steering Committee Australia |
1/1/2010 - | Editorial Board | British Journal of Clinical Pharmacology Australia |
1/1/2010 - | Editorial Board | Therapeutic Advances in Drug Safety Australia |
1/1/2010 - | Membership | Association of Scientific and Clinical Pharmacologists and Toxicologists Australia |
1/1/2010 - | Membership | Australian Society of Clinical and Experimental Pharmacologists and Toxicologists Australia |
1/1/2010 - | Membership | Clinical Advisory Group “Closing the Divide in Indigenous Cancer” Queensland Institute Medical Research Australia |
1/1/2010 - | Membership | Editorial Advisory Group National Prescribing Service Australia |
1/1/2010 - | Membership | PAH Clinical Council Australia |
1/1/2010 - | Membership | UQ Discipline of Medicine Research Symposium Organising Committee and Sessional Chair Australia |
1/1/2010 - | Membership | University of South Australia Sansom Institute Research Advisory Board Australia |
1/1/2009 - | Membership | Medical Journal of Australia (MJA) Insight; Australian Doctor Australia |
1/1/2008 - | Membership | QH Medicines Advisory Committee Australia |
1/1/2008 - | Membership | Queensland Health Medicines Advisory Committee Australia |
1/1/2007 - | Editorial Board | Australian Prescriber Australia |
1/1/2007 - | Editorial Board | Internal Medicine Journal Australia |
1/1/2007 - | Membership | Pharmacogenetics; Education ASCEPT (SIG) Australia |
1/1/2007 - | Membership | Medical Observer Australia |
1/1/2006 - | Editorial Board | Australian Medicine Handbook Australia |
1/1/2005 - 31/12/2009 | Membership | Therapeutic Guidelines Working Group Australia |
Awards
Recipient
Year | Award |
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2014 |
Finalist Royal Australasian College of Physicians Teaching Award Royal Australiasian College of Physicians (RACP) |
2010 |
Finalist Clinical Educator of the Year Postgraduate Medical Council Queensland (Australia) |
2010 |
Nominee Teaching Award for Junior Medical Staff PA (Princess Alexandra Hospital) Health Symposium |
Recognition
Year | Award |
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1999 |
"Best Registrar" teaching award for 5th year medical students Christchurch School of Medicine, Otago University (New Zealand) |
1998 |
"Best Registrar" teaching award for 4th year medical students Christchurch School of Medicine, Otago University (New Zealand) |
Research Award
Year | Award |
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2014 |
University of Queensland Teaching Award RBWH Clinical School, Faculty of Health Sciences, University of Queensland (Australia) |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (18 outputs)
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2022 |
Navani V, Graves MC, Mandaliya H, Hong M, Van Der Westhuizen A, Martin J, Bowden NA, 'Melanoma: An immunotherapy journey from bench to bedside', Cancer Immunotherapies. Solid Tumors and Hematologic Malignancies, Springer, Cham, Switzerland 49-89 (2022) [B1]
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2022 |
Navani V, Graves MC, Mandaliya H, Hong M, Van Der Westhuizen A, Martin J, Bowden NA, 'Melanoma: An immunotherapy journey from bench to bedside', Cancer Immunotherapies. Solid Tumors and Hematologic Malignancies, Springer, Cham, Switzerland 49-89 (2022) [B1]
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2018 |
Martin JH, 'Pharmacology', Geriatric Medicine: A Problem-Based Approach, Springer, Singapore 43-57 (2018) [B1]
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2016 |
Martin JH, 'Issues of Pharmacogenomics in Monitoring Warfarin Therapy', Clinical Challenges in Therapeutic Drug Monitoring, Elsevier, Netherlands 261-270 (2016) [B1]
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Show 15 more chapters |
Journal article (330 outputs)
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2024 |
Moniruzzaman M, Janjua TI, Martin JH, Begun J, Popat A, 'Cannabidiol - Help and hype in targeting mucosal diseases.', J Control Release, 365 530-543 (2024) [C1]
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2024 |
Shafiei M, Galettis P, Beale P, Martin JH, McLachlan AJ, Blinman P, 'Comparison of capecitabine concentrations determined by microsampling versus plasma concentrations for therapeutic drug monitoring: a pilot study.', J Pharm Pharmacol, 76 86-92 (2024) [C1]
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2024 |
Erku D, Martin JH, Michael M, Galettis P, Scuffham P, 'Economic evaluation of personalized vs. standard dosing of 5-fluorouracil in first-line chemotherapy for metastatic colorectal cancer in Australia.', Br J Clin Pharmacol, (2024) [C1]
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2024 |
Martin JH, Galettis P, Flynn A, Schneider J, 'Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors.', Pharmacol Res Perspect, 12 e1182 (2024)
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2024 |
Radovanovic M, Galettis P, Flynn A, Martin JH, Schneider JJ, 'Paclitaxel and Therapeutic Drug Monitoring with Microsampling in Clinical Practice', Pharmaceuticals, 17 (2024) [C1]
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2024 |
Glewis S, Lingaratnam S, Krishnasamy M, Martin JH, Tie J, Alexander M, Michael M, 'Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists', JOURNAL OF ONCOLOGY PHARMACY PRACTICE, 30 30-37 (2024) [C1]
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2023 |
Islam S, Rahaman MH, Yu M, Noll B, Martin JH, Wang S, Head R, 'Anti-Leukaemic Activity of Rilpivirine Is Mediated by Aurora A Kinase Inhibition.', Cancers (Basel), 15 (2023) [C1]
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2023 |
Shafiei M, Mahmood A, Beale P, Galettis P, Martin J, McLachlan AJ, Blinman P, 'Dried Blood Spot Sampling in the Monitoring of Anticancer Therapy for Solid Tumors: A Systematic Review.', Therapeutic drug monitoring, 45 293-305 (2023) [C1]
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2023 |
Milliken E, Galettis P, Martin J, 'A review of psilocybin: chemistry, clinical uses and future research directions', AUSTRALIAN JOURNAL OF CHEMISTRY, 76 258-263 (2023) [C1]
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2023 |
Glewis S, Krishnasamy M, Lingaratnam S, Harris S, Underhill C, Georgiou C, et al., 'Patient and healthcare professional acceptability of pharmacogenetic screening for DPYD and UGT1A1: A cross sectional survey.', Clin Transl Sci, 16 2700-2708 (2023) [C1]
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2023 |
Urbaniak A, Thummel KE, Alade AN, Rettie AE, Prasad B, De Nicolò A, et al., 'Experimental pharmacology in precision medicine.', Pharmacol Res Perspect, 11 e01147 (2023) [C1]
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2023 |
Tong Z, Esser L, Galettis P, Rudd D, Easton CD, Nilghaz A, et al., 'Fluoropolymer Functionalization of Organ-on-Chip Platform Increases Detection Sensitivity for Cannabinoids', Biosensors, 13 779-779 [C1]
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2023 |
Shafiei M, Galettis P, Beale P, Reuter SE, Martin JH, McLachlan AJ, Blinman P, 'Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a pilot study', Cancer Chemotherapy and Pharmacology, 92 135-139 (2023) [C1] Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate th... [more] Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate the pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (< 70¿years) and older adults (= 70¿years) receiving capecitabine for solid cancer. Methods: Eligible participants receiving capecitabine had 2 venous samples collected on day 14 of cycle 1 and cycle 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used to generate individual estimates of PK parameters for 5-FU. A linear mixed-effect analysis of variance (ANOVA) model was used to compare dose-normalised log-transformed PK parameters between age groups. Correlations were determined by linear regression and logistic regression analyses. Results: Of the total 26 participants, 58% were male with a median age of 67¿years (range, 37¿85) with 54% aged < 70¿years and 46% aged = 70¿years. Participants aged = 70¿years, compared to those aged < 70¿years, had a greater 5-FU exposure based on area under the concentration¿time curve (AUC) of 17% (90% CI 103¿134%; 0.893 vs. 0.762¿mg h/L) and 14% increase in maximal concentration, Cmax (90% CI 82.1¿159%; 0.343 vs. 0.300¿mg/L). The 5-FU Cmax was positively associated with time up and go (TUG) (Pearson¿s correlation 0.77, p = 0.01), but not other geriatric assessment domains or severe toxicity. Conclusion: 5-FU exposure was significantly increased in older adults compared to younger adults receiving equivalent doses of capecitabine, and is a possible cause for increased toxicity in older adults.
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2023 |
Chin PKL, Charles K, Murnion B, McGuire TM, Hilmer SN, Martin J, et al., 'Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand.', Br J Clin Pharmacol, 89 3105-3115 (2023) [C1]
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2023 |
Martin JH, 'The valley of death: why Australia failed to develop clinically effective drugs in COVID-19.', Intern Med J, 53 2175-2179 (2023) [C1]
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2023 |
Popovic M, Martin JH, Head RJ, 'COVID infection in 4 steps: Thermodynamic considerations reveal how viral mucosal diffusion, target receptor affinity and furin cleavage act in concert to drive the nature and degree of infection in human COVID-19 disease', Heliyon, 9 (2023) [C1] We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiote... [more] We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiotensin converting enzyme 2 (ACE2) target. Utilising the structural similarity of SARS-CoV and SARS-CoV-2 and a shared viral target receptor (ACE2), but a dramatic difference in upper or lower respiratory tract infectivity, we were able to generate insights into the linkage of mucosal diffusion and target receptor affinity in determining the pathophysiological pathways of these two viruses. Our analysis reveals that for SARS-CoV-2 the higher affinity of ACE2 binding, the faster and more complete the mucosal diffusion in its transport from the upper airway to the region of the ACE2 target on the epithelium. This diffusional process is essential for the presentation of this virus to the furin catalysed highly efficient entry and infection process in the upper respiratory tract epithelial cells. A failure of SARS-CoV to follow this path is associated with lower respiratory tract infection and decreased infectivity. Thus, our analysis supports the view that through tropism SARS-CoV-2 has evolved a highly efficient membrane entry process that can act in concert with a high binding affinity of this virus and its variants for its ACE2 which in turn promotes enhanced movement of the virus from airway to epithelium. In this way ongoing mutations yielding higher affinities of SARS-CoV-2 for the ACE2 target becomes the basis for higher upper respiratory tract infectivity and greater viral spread. It is concluded that SARS-CoV-2 is constrained in the extent of its activities by the fundamental laws of physics and thermodynamics. Laws that describe diffusion and molecular binding. Moreover it can be speculated that the very earliest contact of this virus with the human mucosa defines the pathogenesis of this infection.
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2023 |
Lorenzetti V, McTavish E, Broyd S, van Hell H, Thomson D, Ganella E, et al., 'Daily Cannabidiol Administration for 10 Weeks Modulates Hippocampal and Amygdalar Resting-State Functional Connectivity in Cannabis Users: A Functional Magnetic Resonance Imaging Open-Label Clinical Trial.', Cannabis Cannabinoid Res, (2023) [C1]
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2023 |
Jake Shortt, Galettis P, Cheah CY, Davis J, Ludford-Menting M, Link EK, et al., 'A phase 1 clinical trial of the repurposable acetyllysine mimetic, n-methyl-2-pyrrolidone (NMP), in relapsed or refractory multiple myeloma', Clinical Epigenetics, 15 (2023) [C1] Background: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Pre... [more] Background: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR¿MM). Secondary endpoints were safety, pharmacokinetics (PK), overall response rate and immunological biomarkers of activity. Results: Thirteen patients received NMP at starting doses between 50 and 400¿mg daily. Intra-patient dose escalation occurred in five patients, with one attaining the ceiling protocolised dose of 1¿g daily. Median number of monthly cycles commenced was three (range 1¿20). Grade 3¿4 adverse events (AEs) were reported in seven (54%; 95% CI 25¿81%) patients. Most common AEs (> 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200¿mg NMP (overall DLT rate 8%; 95% CI 0¿36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29¿539) days and 33 (95% CI 9.7¿ > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39¿91%). PK analysis demonstrated proportional dose¿concentrations up to 400¿mg daily, with a more linear relationship above 500¿mg. Maximum plasma concentrations (Cmax) of 16.7¿mg/L at the 800¿mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12¿months. Conclusions: NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR¿MM; an MTD was not determined up to a maximum dose of 1¿g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.
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2023 |
Abdel Shaheed C, Hayes C, Maher CG, Ballantyne JC, Underwood M, McLachlan AJ, et al., 'Opioid analgesics for nociceptive cancer pain: A comprehensive review.', CA Cancer J Clin, (2023) [C1]
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2023 |
Graham M, Renaud E, Lucas CJ, Schneider J, Martin JH, 'Medicinal Cannabis Guidance and Resources for Health Professionals to Inform Clinical Decision Making.', Clin Ther, 45 527-534 (2023) [C1]
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2022 |
Martin JH, Patel J, 'Complementary and alternative therapies in the palliative setting', INTERNAL MEDICINE JOURNAL, 52 1677-1684 (2022) [C1]
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2022 |
Liu Z, Martin JH, Liauw W, Mclachlan S-A, Link E, Matera A, et al., 'Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites', EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 78 53-64 (2022) [C1]
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2022 |
Graham M, Martin JH, Lucas CJ, Murnion B, Schneider J, 'Cannabidiol drug interaction considerations for prescribers and pharmacists', EXPERT REVIEW OF CLINICAL PHARMACOLOGY, 15 1383-1397 (2022) [C1]
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2022 |
Islam S, Teo T, Kumarasiri M, Slater M, Martin JH, Wang S, Head R, 'Combined In Silico and In Vitro Evidence Supporting an Aurora A Kinase Inhibitory Role of the Anti-Viral Drug Rilpivirine and an Anti-Proliferative Influence on Cancer Cells', PHARMACEUTICALS, 15 (2022) [C1]
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2022 |
Glewis S, Alexander M, Khabib MNH, Brennan A, Lazarakis S, Martin J, et al., 'A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing', BRITISH JOURNAL OF CANCER, 127 126-136 (2022) [C1]
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2022 |
Hurley EN, Ellaway CJ, Johnson AM, Truong L, Gordon R, Galettis P, et al., 'Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial', EPILEPSIA, 63 1736-1747 (2022) [C1]
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2022 |
Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH, '"LONG COVID"-A hypothesis for understanding the biological basis and pharmacological treatment strategy', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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2022 |
Lumbers ER, Head R, Smith GR, Delforce SJ, Jarrott B, Martin JH, Pringle KG, 'The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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2022 |
Head RJ, Lumbers ER, Jarrott B, Tretter F, Smith G, Pringle KG, et al., 'Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and response to treatment', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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2022 |
de Witt A, Matthews V, Bailie R, Valery PC, Adams J, Garvey G, et al., 'Aboriginal and Torres Strait Islander patients cancer care pathways in Queensland: Insights from health professionals', Health Promotion Journal of Australia, 33 701-710 (2022) [C1] Objective: To identify points for improvements within the health system where Aboriginal and Torres Strait Islander cancer patients may experience a lack of continuity in their ca... [more] Objective: To identify points for improvements within the health system where Aboriginal and Torres Strait Islander cancer patients may experience a lack of continuity in their cancer care. The optimal care pathway for Aboriginal and Torres Strait Islander people with cancer (OCP) framework was utilised as a tool in this work. Methods: Semi-structured interviews were conducted with health professionals at the primary health care (PHC) and hospital setting. Data were categorised into six steps using the OCP framework. Results: This study identified multiple time-points in the cancer pathways that could be strengthened to increase the continuity of cancer care for these patients. In addition, the provision of person-centred care and adequate education tailored to patients' and health professionals' needs can help minimise the likelihood of patients experiencing a lack of continuity in their cancer care. Participants were recruited from an urban hospital (n¿=¿9) and from six Aboriginal Community Controlled Health Services (n¿=¿17) across geographical locations in Queensland. The provision of culturally competent care, effective communication, coordination and collaboration between services along the cancer pathway from prevention and early diagnosis through to end-of-life care were highlighted as important to enhance care continuity for Indigenous Australians. Conclusion: The implementation of recommendations outlined in the OCP framework may help with improving cancer care continuity for Indigenous patients with cancer. Summary: Aboriginal and Torres Strait Islander people can sometimes find cancer care pathways complex and difficult to navigate. This study identified points in the cancer pathways that could be strengthened to increase the continuity of cancer care for these patients which could potentially lead to improved outcomes.
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2022 |
Bonomo Y, Norman A, Collins L, O Neill H, Galettis P, Trinca J, et al., 'Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study', Pain and Therapy, 11 171-189 (2022) [C1] Introduction: This phase¿I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydroca... [more] Introduction: This phase¿I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydrocannabinol [THC]/cannabidiol [CBD]) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia. Methods: Nine people with CNCP and oral morphine equivalent daily dose of 60¿mg or higher were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC), and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5¿mg THC/2.5¿mg CBD on day¿1, and daily escalating doses up to a single dose of 12.5¿mg THC/12.5¿mg CBD on day¿29. Follow-up was on day¿36 after a 7-day washout. Secondary outcome data encompassed pain, mood, and sleep parameters. Results: The parent compounds THC, and CBD, and metabolites OH-THC and COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2¿h post-administration, decreasing to approximately pre-dose concentrations by 8¿h. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one adverse event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed. Conclusion: The THC/CBD formulation was tolerated well in a group of patients with CNCP. Between-participant variability supports personalized dosing and ¿start low¿go slow¿ titration. To validate and quantify improvements in secondary efficacy outcomes a randomized placebo-controlled study is needed. Trial Registration: Australian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).
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2022 |
Razmovski-Naumovski V, West PA, Bellemore F, Byfieldt N, Bellamy D, Chye R, et al., 'Defining the trials nurses role in operationalising a medicinal cannabis clinical trial', Collegian, 29 370-378 (2022) [C1] Background: With increasing use of medicinal cannabis for symptom management, clinical trials nurses need to consider the various legal, social, ethical, and interdisciplinary car... [more] Background: With increasing use of medicinal cannabis for symptom management, clinical trials nurses need to consider the various legal, social, ethical, and interdisciplinary care issues of implementing these clinical trials, especially in a palliative care population. Aim: To define the trials nurses¿ role in operationalising a medicinal cannabis pharmacokinetic inpatient trial in an advanced cancer population. Methods: A qualitative, descriptive design incorporating case study methodology was used. Data were collected from minuted meetings, field notes, telephone, and email discussions involving trials nurses at two palliative care sites. Data were integrated and synthesised to identify the key considerations required to operationalise the trial and define the trials nurses¿ role. Findings: Three key considerations were identified: (i) Normalising the trial, (ii) Creating the environment to undertake the trial, and (iii) Managing the complexity. The trials nurses¿ role was explored through subthemes of these considerations including: their understanding of the purpose of the research and training in the protocol; organising inpatient resources, pharmacy requirements and managing the external scrutiny; participant recruitment, staffing requirements, safety, and supporting caregivers. Discussion: This study emphasises the multifactorial role of the trials nurses in managing a complex palliative care trial, and the importance of their early involvement and recognition as the vital link between all parties. Conclusion: Defining the trials nurses¿ role, within the confines of the protocol, the context of efficient nursing processes and ensuring a patient-centred approach enabled the operationalisation of a Phase I/II medicinal cannabis trial which will have global impact.
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2022 |
Graham M, Bird S, Howard Z, Dobson M, Palazzi K, Lucas CJ, et al., 'NSW Cannabis Medicines Advisory Service preliminary survey results: enquirer perceptions and patient outcomes.', Intern Med J, 52 228-237 (2022) [C1]
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2022 |
Lawson J, O'Brien T, Graham M, Renaud E, Jones D, Freeman J, et al., 'Expert advice for prescribing cannabis medicines for patients with epilepsy-drawn from the Australian clinical experience', BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 88 3101-3113 (2022) [C1]
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2022 |
Bhattacharya J, Booy R, Casadevall A, Dela Cruz C, Fedson DS, Garcia JGN, et al., 'A practical treatment for COVID-19 and the next pandemic', PHARMACOLOGY RESEARCH & PERSPECTIVES, 10 (2022) [C1]
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2022 |
Islam S, Wang S, Bowden N, Martin J, Head R, 'Repurposing existing therapeutics, its importance in oncology drug development: Kinases as a potential target', BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 88 64-74 (2022) [C1]
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2022 |
Radovanovic M, Schneider JJ, Shafiei M, Martin JH, Galettis P, 'Measurement of 5- fluorouracil, capecitabine and its metabolite concentrations in blood using volumetric absorptive microsampling technology and LC-MS/MS', Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1188 (2022) [C1] 5-fluorouracil (5-FU) and its oral formulation, capecitabine, are widely used in treating a range of malignancies, either alone or in combination with other antineoplastic drugs. ... [more] 5-fluorouracil (5-FU) and its oral formulation, capecitabine, are widely used in treating a range of malignancies, either alone or in combination with other antineoplastic drugs. Body surface area-based dosing is used for these agents, despite this approach leading to substantial variability in drug exposure and often resulting in either toxicity or treatment failure. Tailoring therapeutic regimens for individual patients using therapeutic drug monitoring (TDM) has been shown to significantly reduce toxicity and improve cancer outcomes. However, for optimum TDM, sample timing is crucial, along with the need for a venepuncture blood sample to obtain the plasma currently used for 5-FU measurement. In addition to complex blood sample handling requirements, large sample volume and frequent sampling required for pharmacokinetic analysis is another barrier to successfully implementing TDM in a healthcare setting. Microsampling is an alternative collection method to venepuncture, which, combined with the now readily available liquid chromatography mass spectrometry (LC-MS/MS) technology, overcomes the plasma-associated issues. It also has the significant advantage of enabling at home and remote sampling, thus facilitating 5-FU TDM in clinical practice. A LC-MS/MS method for simultaneous measurement of capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-FU using Mitra® microsampling devices for sample collection was developed. A Shimadzu 8060 LC-MS/MS equipped with electrospray ionisation source interface, operated in positive and negative ion modes, with reversed-phase chromatographic separation was employed for sample analysis. Samples were extracted from Mitra® devices using acetonitrile containing stable isotope-labelled internal standards, sonicated, evaporated under vacuum and resuspended in 0.1 % formic acid before injection into the LC-MS/MS. Chromatographic separation was on a Luna Omega Polar C18 (100 × 2.1 mm, 1.6 µm) column with gradient elution of 0.1 % formic acid in water and acetonitrile. Total run time was 5 min, with the injection volume of 1 µL. The intra and inter-day imprecision ranged from 3.0 to 8.1 and 6.3¿13.3 % respectively. Accuracy ranged from 95 -114 % for all analytes. Lower limit of quantification with imprecision of < 19 % and accuracy between 89 and 114 % was 0.05 mg/L for 5-FU and 10 µg/L for other analytes. Assays were linear from 0.05 to 50 mg/L for 5-FU and 10¿10,000 µg/L for all other analytes. Analytes were stable on Mitra® devices for up to 9 months at room temperature, 2 years at -30 ¿ and 3 days at 50 ¿. The method was successfully applied for the analysis of samples from patients undergoing cancer treatment with 5-FU and capecitabine. Microsampling using volumetric absorptive microsampling proved to be as reliable as conventional blood collection for 5-FU and capecitabine. This sampling technique may lead to less invasive and better-timed sample collection for TDM, supporting dose optimization strategy.
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2022 |
Liu Z, Julsgaard M, Zhu X, Martin J, Barclay ML, Cranswick N, et al., 'Timing of Live Attenuated Vaccination in Infants Exposed to Infliximab or Adalimumab in Utero: A Prospective Cohort Study in 107 Children', Journal of Crohn's and Colitis, 16 1835-1844 (2022) [C1] Background and Aims: For infants exposed in utero to anti-tumour necrosis factor-a [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug i... [more] Background and Aims: For infants exposed in utero to anti-tumour necrosis factor-a [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy. Methods: We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included. Results: Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n=25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n=3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/. Conclusions: Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample =1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.
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2021 |
Martin JH, Head R, 'A pharmacological framework for integrating treating the host, drug repurposing and the damage response framework in COVID-19', British Journal of Clinical Pharmacology, 87 875-885 (2021) [C1] With any new disease a framework for the development of preventative or treatment therapeutics is key; the absence of such in COVID-19 has enabled ineffective and potentially unsa... [more] With any new disease a framework for the development of preventative or treatment therapeutics is key; the absence of such in COVID-19 has enabled ineffective and potentially unsafe treatments to be taken up by governments and clinicians desperate to have options for patients. As we still have few therapies and nil vaccines yet available, the void of a clear framework for research and practice is increasingly clear. We describe a framework that has been used to prioritise therapeutic research in previous pandemics which could be used to progress clinical pharmacology and therapeutics research in COVID-19. This is particularly relevant as discussion has already moved on from antiviral therapeutics to delineating the treatment of the host from treatment and elimination of the infective agent. Focussing on the host brings together three concepts: host treatment, the damage response framework and therapeutic repurposing. The integration of these three areas plays to the traditional strength of pharmaceuticals in providing a period of stabilization to permit time for the development of novel antiviral drugs and vaccines. In integrating approaches to repurposing, host treatment and damage response we identified three key properties that a potentially effective repurposed drug must possess by way of a framework. There must be homology, i.e., the same or similar relation with the pathogenesis of the disease, ideally targeted to the conserved pathophysiological outcomes of the viral attack; there must be a defined locus within the spectrum to prevention to severe disease and the framework must draw upon the historical dose and safety experience of the repurposed drug. To illustrate, we have mapped therapeutics that impact upon a key dysregulated pathway in COVID-19 ¿ the renin angiotensin system ¿ using this approach. Collectively this type of analysis reveals the importance of existing data (repurposed information and administrative observational data) and the importance of the details of the known pathophysiological response to viruses in approaches to treating the host.
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2021 |
Chatelut E, Hendrikx JJMA, Martin J, Ciccolini J, Moes DJAR, 'Unraveling the complexity of therapeutic drug monitoring for monoclonal antibody therapies to individualize dose in oncology', Pharmacology Research and Perspectives, 9 (2021) [C1] Monoclonal antibodies (Mabs) have become key drugs in cancer treatment, either as targeted therapies or more recently as immune checkpoint inhibitors (ICIs). The fact that only so... [more] Monoclonal antibodies (Mabs) have become key drugs in cancer treatment, either as targeted therapies or more recently as immune checkpoint inhibitors (ICIs). The fact that only some patients benefit from these drugs poses the usual question in the field of onco-hematology: that of the benefit of individual dosing and the potential of therapeutic drug monitoring (TDM) to carry out this individualization. However, Mabs present unique pharmacological characteristics for TDM, and the pharmacokinetic¿pharmacodynamic relationship observed should be interpreted differently than that observed for conventional drugs and small molecules. This pharmacology practice review has been summarized from a public debate between the authors at the International TDM and Clinical Toxicology meeting in Banff, 2020, regarding the potential roles of TDM in the Mab/ICI setting.
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2021 |
Galettis P, Williams M, Gordon R, Martin JH, 'A Simple Isocratic HPLC Method for the Quantitation of 17 Cannabinoids', AUSTRALIAN JOURNAL OF CHEMISTRY, 74 453-462 (2021) [C1]
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2021 |
Schneider JJ, Galettis P, Martin JH, 'Overcoming barriers to implementing precision dosing with 5-fluorouracil and capecitabine', BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 87 317-325 (2021) [C1]
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2021 |
Clarke WA, Chatelut E, Fotoohi AK, Larson RA, Martin JH, Mathijssen RHJ, Salamone SJ, 'Therapeutic drug monitoring in oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology consensus guidelines for imatinib therapy', EUROPEAN JOURNAL OF CANCER, 157 428-440 (2021) [C1]
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2021 |
Hayward KL, Valery PC, Patel PJ, Li C, Horsfall LU, Wright PL, et al., 'Medication Discrepancies and Regimen Complexity in Decompensated Cirrhosis: Implications for Medication Safety', PHARMACEUTICALS, 14 (2021) [C1]
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2020 |
Meiklejohn JA, Bailie R, Adams J, Garvey G, Bernardes CM, Williamson D, et al., '"I'm a Survivor": Aboriginal and Torres Strait Islander Cancer Survivors' Perspectives of Cancer Survivorship.', Cancer nursing, 43 105-114 (2020) [C1]
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2020 |
Chew HY, De Lima PO, Gonzalez Cruz JL, Banushi B, Echejoh G, Hu L, et al., 'Endocytosis Inhibition in Humans to Improve Responses to ADCC-Mediating Antibodies', Cell, 180 895-914.e27 (2020) [C1]
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2020 |
Dryburgh LM, Martin JH, 'Using Therapeutic Drug Monitoring and Pharmacovigilance to Overcome Some of the Challenges of Developing Medicinal Cannabis from Botanical Origins', Therapeutic Drug Monitoring, 42 98-101 (2020) [C1] Purpose: Plants belonging to the genus Cannabis have been domesticated and used by humans for millennia. Thought to have originated from central Asia, cannabis has been harnessed ... [more] Purpose: Plants belonging to the genus Cannabis have been domesticated and used by humans for millennia. Thought to have originated from central Asia, cannabis has been harnessed for its nutritional, therapeutic, and psychoactive properties, and as a source of fiber (Office of Medicinal Cannabis. Analytical Monograph Cannabis Flos. Den Haag, The Netherlands: Office of Medicinal Cannabis; 2014). Human use of cannabis is not novel; however, its medicalization offers a new pharmacotherapeutic frontier. Methods: The authors recently reported a systematic review of the contaminants of cannabis (National Academies of Sciences Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC; 2017). This article draws on the research limitations identified by that review and examines a collection of the relevant literature to provide an appreciation of the current evidence base. Results: The review explores the current status of cannabis in medical use, the drug development aspects that apply when taking a plant through to pill development, and the roles that therapeutic drug monitoring and pharmacovigilance have to guide practice until the drug development information on medicinal cannabis preparations is complete. Conclusions: A surge of public and clinical interest in the possible therapeutic applications of constituent cannabinoids has potentiated global legislative and policy reform. However, our understanding of its properties, optimized use, and harmful effects remains incomplete (Therapeutic Goods Administration. Guidance for the use of medicinal cannabis in Australia In: Department of Health Department, editor. Woden ACT Australian Government 2017; Dryburgh LM, Bolan NS, Grof CP, Galettis P, Schneider J, Lucas CJ, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Brit J Clin Pharm. 2018;84(11):2468¿2476). In particular, a comprehensive appreciation of its toxicity profile is lacking.
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2020 |
Harris BDW, Phan V, Perera V, Szyc A, Galettis P, Martin JH, et al., 'Inability of Current Dosing to Achieve Carboplatin Therapeutic Targets in People with Advanced Non-Small Cell Lung Cancer: Impact of Systemic Inflammation on Carboplatin Exposure and Clinical Outcomes', Clinical Pharmacokinetics, 59 1013-1026 (2020) [C1] Background: The presence of elevated systemic inflammation in people with advanced non-small cell lung cancer (NSCLC) is associated with significantly shorter survival following c... [more] Background: The presence of elevated systemic inflammation in people with advanced non-small cell lung cancer (NSCLC) is associated with significantly shorter survival following carboplatin-based chemotherapy. Objective: This study investigated whether novel factors, such as systemic inflammation [platelet¿lymphocyte ratio (PLR) and neutrophil¿lymphocyte ratio (NLR)], impact carboplatin pharmacokinetics and drug utilisation. The study also examined the ability of current and alternate dosing regimens to meet therapeutic targets. Methods: Seventy-two people with advanced NSCLC treated with carboplatin-based (460¿1050 mg) doublet chemotherapy were recruited and pharmacokinetic data (n = 61) were analysed using non-linear mixed modelling. Covariate analysis was performed to investigate the impact of standard and novel patient characteristics of carboplatin pharmacokinetics. A Monte Carlo simulation of 100,000 representative NSCLC patients evaluated the ability of the Calvert formula and novel dosing strategies to achieve the targeted therapeutic range. The associations between systemic inflammation and chemotherapy drug utilisation (cycles received, relative dose intensity (RDI) and second-line uptake) and clinical endpoints were also investigated in the pharmacokinetic cohort, and two independent cohorts of people with advanced NSCLC from the Chemotherapy Dosing in Cancer-Related Inflammation (CDCRI) database¿that were administered carboplatin¿paclitaxel (n = 37) or carboplatin¿gemcitabine (n = 358). Results: In all cohorts, 25¿53% of people had elevated systemic inflammation (NLR > 5 or PLR > 300). In the pharmacokinetic cohort, no patients achieved the desired therapeutic target of carboplatin. Carboplatin exposure was related to renal function, as estimated using the Cockcroft¿Gault formula, albumin and inflammation (NLR). In the pharmacokinetic cohort, increasing carboplatin area under the curve (AUC) correlated with greater reductions in red blood cells and haemoglobin. In this cohort, the average measured AUC of partial responders was 2.4¿mg·min/mL. Also in the pharmacokinetic cohort, only 12% of people with an NLR > 5 received four or more cycles of chemotherapy, compared with 62% of patients with an NLR = 5 (p < 0.001). For people in the CDCRI cohort receiving carboplatin¿gemcitabine, those with an NLR > 5 also received less cycles (four or more cycles, 41% vs. 60%; p < 0.01) as well as less second-line chemotherapy (46% vs. 60%; p = 0.02) compared with patients without inflammation. People in the pharmacokinetic cohort with an NLR > 5 had 12¿months less median survival compared with people with an NLR = 5 (6.5 vs. 18¿months; p = 0.08). Similarly, overall survival was significantly shortened in people in the CDCRI cohort receiving carboplatin¿gemcitabine with an NLR > 5 compared with those with an NLR = 5 (7 vs. 12¿months; p < 0.001), and Cox regression analysis showed a 1.5-fold (1.3¿2.1; p < 0.001) increased hazard of death associated with the increased systemic inflammation. Simulations of the newly developed model-based and Calvert dosing assessed the ability to reach this study¿s proposed actual target AUC of 2.2¿2.6¿mg·min/mL. These showed current Calvert dosing was predicted to result in substantial overexposure in patients with high systemic inflammation. The newly developed model showed equivalent levels of carboplatin therapeutic target achievement across the spectrum of inflammation observed in the lung cancer population. Conclusion: An alternate model-based dosing strategy for carboplatin was developed and is predicted to result in consistent drug exposure across the population and improve attainment of therapeutic targets. Further studies of this new model are warranted in people with advanced NSCLC.
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2020 |
Hayward KL, Valery PC, Patel PJ, Horsfall LU, Wright PL, Tallis CJ, et al., 'Effectiveness of patient-oriented education and medication management intervention in people with decompensated cirrhosis', Internal Medicine Journal, 50 1142-1146 (2020) [C1]
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2020 |
Martin JH, Hall W, Fitzcharles MA, Borgelt L, Crippa J, 'Ensuring access to safe, effective, and affordable cannabis-based medicines', British Journal of Clinical Pharmacology, 86 630-634 (2020) [C1]
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2020 |
Liu Z, Galettis P, Broyd SJ, van Hell H, Greenwood LM, de Krey P, et al., 'Model-based analysis on systemic availability of co-administered cannabinoids after controlled vaporised administration', Internal Medicine Journal, 50 846-853 (2020) [C1] Background: The most important two medicinal cannabinoids are ¿9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic ... [more] Background: The most important two medicinal cannabinoids are ¿9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic availability, lower individual variability and faster drug delivery. Although it is common THC is co-administered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. Aims: To investigate the influence of different doses of co-administered CBD on the systemic availability of THC, and to compare the availability of THC and CBD in a sample of frequent and infrequent cannabis users. Methods: The study used a randomised, double-blind, crossover placebo-controlled design. THC and/or CBD in ethanol was vaporised and inhaled. Plasma concentrations of THC and CBD were analysed. The THC data created in this study were pooled together with published THC pharmacokinetic data in order to cover all the phases of THC disposition. Population pharmacokinetic model of THC was developed based on the pooled data. The model of CBD was developed based on the data created in this study. Results: Population pharmacokinetic models of THC and CBD were developed. With concomitant inhalation of high-dose CBD, the systemic availability of THC decreased significantly. Frequent cannabis users appeared to have higher systemic availability of THC and CBD when high-dose CBD was administered. Conclusions: The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the ¿real-world¿ setting.
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2020 |
Patel J, Lucas CJ, Ryan J, Jenkins M, Martin JH, 'Vancomycin therapeutic drug monitoring in paediatrics', Journal of Paediatrics and Child Health, 56 563-570 (2020) [C1] Aim: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus ... [more] Aim: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration¿time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. Methods: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. Results: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05¿86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0¿39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. Conclusion: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.
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2020 |
de Witt A, Matthews V, Bailie R, Garvey G, Valery PC, Adams J, et al., 'Communication, collaboration and care coordination: The three-point guide to cancer care provision for aboriginal and Torres Strait Islander Australians', International Journal of Integrated Care, 20 1-16 (2020) [C1] Aim: To explore health professionals¿ perspectives on communication, continuity and between-service coordination for improving cancer care for Indigenous people in Queensland. Met... [more] Aim: To explore health professionals¿ perspectives on communication, continuity and between-service coordination for improving cancer care for Indigenous people in Queensland. Methods: Semi-structured interviews were conducted in a purposive sample of primary health care (PHC) services in Queensland with Indigenous and non-Indigenous health professionals who had experience caring for Indigenous cancer patients in the PHC and hospital setting. The World Health Organisation integrated people-centred health services framework was used to analyse the interview data. Results: Seventeen health staff from six Aboriginal Community Controlled Services and nine health professionals from one tertiary hospital participated in this study. PHC sites were in urban, regional and rural settings and the hospital was in a major city. Analysis of the data suggests that timely communication and information exchange, collaborative approaches, streamlined processes, flexible care delivery, and patient-centred care and support were crucial in improving the continuity and coordination of care between the PHC service and the treating hospital. Conclusion: Communication, collaboration and care coordination are integral in the provision of quality cancer care for Indigenous Australians. It is recommended that health policy and funding be designed to incorporate these aspects across services and settings as a strategy to improve cancer outcomes for Indigenous people in Queensland.
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2020 |
Valery PC, Bernardes CM, de Witt A, Martin J, Walpole E, Garvey G, et al., 'Are general practitioners getting the information they need from hospitals and specialists to provide quality cancer care for Indigenous Australians?', Internal Medicine Journal, 50 38-47 (2020) [C1] Background: Cancer care involves many different healthcare providers. Delayed or inaccurate communication between specialists and general practitioners (GP) may negatively affect ... [more] Background: Cancer care involves many different healthcare providers. Delayed or inaccurate communication between specialists and general practitioners (GP) may negatively affect care. Aim: To describe the pattern and variation of communication between primary healthcare (PHC) services and hospitals and specialists in relation to the patient's cancer care. Methods: A retrospective audit of clinical records of Indigenous Australians diagnosed with cancer during 2010¿2016 identified through 10 PHC services in Queensland is described. Poisson regression was used to model the dichotomous outcome availability of hospital discharge summary versus not. Results: A total of 138 patient records was audited; 115 of those patients visited the PHC service for cancer-related care after cancer diagnosis; 40.0% visited the service before a discharge summary was available, and 36.5% of the patients had no discharge summary in their medical notes. While most discharge summaries noted important information about the patient's cancer, 42.4% lacked details regarding the discharge medications regimen. Conclusions: Deficits in communication and information transfer between specialists and GP may adversely affect patient care. Indigenous Australians are a relatively disadvantaged group that experience poor health outcomes and relatively poor access to care. The low proportion of discharge summaries noting discharge medication regimen is of concern among Indigenous Australians with cancer who have high comorbidity burden and low health literacy. Our findings provide an insight into some of the factors associated with quality of cancer care, and may provide guidance for focus areas for further research and improvement efforts.
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2020 |
O'Hara K, Martin JH, Schneider JJ, 'Barriers and Challenges in Performing Pharmacokinetic Studies to Inform Dosing in the Neonatal Population.', Pharmacy (Basel, Switzerland), 8 1-6 (2020) [C1]
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2020 |
Koyanagi M, Anning R, Loewenthal M, Martin JH, 'Vancomycin: Audit of American guideline-based intermittent dose administration with focus on overweight patients', British Journal of Clinical Pharmacology, 86 958-965 (2020) [C1] Aims: Vancomycin dosing and monitoring recommendations are poorly adhered to in many institutions internationally, with concerns of treatment failure and propelling antibiotic res... [more] Aims: Vancomycin dosing and monitoring recommendations are poorly adhered to in many institutions internationally, with concerns of treatment failure and propelling antibiotic resistance. The primary aim of this study was to audit the rate of adherence to American guidelines, with particular interest in loading dose administration. The secondary aims were (i) to determine whether or not guideline adherence results in therapeutic concentrations across body mass index (BMI) groups and (ii) to determine whether or not this was in turn associated with morbidity and hospital mortality. Method: Data were collected in a single tertiary hospital on all patients who had two or more serum vancomycin concentrations measured. Result: In total, 107 patients met the inclusion criteria. Overall, 38.3% of patients were commenced on guideline adherent vancomycin doses, and 28.3% of overweight patients received an adherent first dose compared to 51.1% of non-overweight people (difference 23%, 95% CI 4% to 41%, P = 0.024). Overweight patients were more frequently underdosed compared to non-overweight patients (P = 0.039). The frequency and proportion of underdosing increased with BMI. Overweight patients spent a smaller fraction of their course within the therapeutic range, although the difference was not statistically significant (difference 7.7%; 95% CI 4% to 19.4%; P = 0.195). The overweight group had longer hospital length of stay (LOS), higher mortality and more treatment failures. Conclusion: Adherence to guideline-based prescription is poor, particularly in overweight patients. Patients who are initially underdosed have fewer therapeutic vancomycin days, regardless of BMI. Overweight patients have increased hospital LOS, hospital mortality and treatment failure.
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2020 |
Valery PC, Bernardes CM, de Witt A, Martin J, Walpole E, Garvey G, et al., 'Patterns of primary health care service use of Indigenous Australians diagnosed with cancer', Supportive Care in Cancer, 28 317-327 (2020) [C1] Purpose: The role of general practitioners in cancer care has expanded in recent years. However, little is known about utilization of primary health care (PHC) services by patient... [more] Purpose: The role of general practitioners in cancer care has expanded in recent years. However, little is known about utilization of primary health care (PHC) services by patients with cancer, particularly among socio-economically disadvantaged groups. We describe utilization of PHC services by patients with cancer, and the nature of the care provided. The study focuses on a disadvantaged group in Australia, namely Indigenous Australians. Methods: A retrospective audit of clinical records in ten PHC services in Queensland, Australia. Demographic and clinical data of Indigenous Australians diagnosed with cancer during 2010¿2016 were abstracted from patient¿s medical records at the PHC services. The rates of cancer-related visits were calculated using person years at risk as a denominator. Results: A total of 138 patients¿ records were audited. During 12¿months following the cancer diagnosis, patients visited the PHC service on average 5.95 times per year. Frequency of visits were relatively high in remote areas and among socioeconomic disadvantaged patients (IRR = 1.87, 95%CI 1.61¿2.17; IRR = 1.79, 95%CI 1.45¿2.21, respectively). Over 80% of visits were for seeking attention for symptoms, wound care, and emotional or social support. Patients who did not undergo surgery, had greater comorbidity, received chemotherapy and/or radiotherapy, and male gender had significantly greater rate of visits than their counterparts. Conclusion: The frequency of utilization of PHC services, especially by patients with comorbidities, and the range of reasons for attendance highlights the important role of PHC services in providing cancer care. The reliance on PHC services, particularly by patients in remote and disadvantaged communities, has important implications for appropriate resourcing and support for services in these locations.
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2019 |
Nicoletti P, Aithal GP, Chamberlain TC, Coulthard S, Alshabeeb M, Grove JI, et al., 'Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles', Clinical Pharmacology and Therapeutics, 106 245-253 (2019) [C1] Some patients prescribed flucloxacillin (~¿0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolida... [more] Some patients prescribed flucloxacillin (~¿0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA-B*57:01 was the major risk factor (allelic odds ratio (OR)¿=¿36.62; P¿=¿2.67¿×¿10-97). HLA-B*57:03 also showed an association (OR¿=¿79.21; P¿=¿1.2¿×¿10-6). Within the HLA-B protein sequence, imputation showed valine97, common to HLA-B*57:01 and HLA-B*57:03, had the largest effect (OR¿=¿38.1; P¿=¿9.7¿×¿10-97). We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n¿=¿6) or amoxicillin (n¿=¿15) and no significant non-HLA signals for any penicillin-related DILI.
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2019 |
Dimmitt SB, Stampfer HG, Martin JH, Ferner RE, 'Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50', British Journal of Clinical Pharmacology, 85 2218-2227 (2019) [C1] Antihypertensive drugs have usually been approved at doses near the top of their respective dose¿response curves. Efficacy plateaus but adverse drug reactions (ADRs), such as fall... [more] Antihypertensive drugs have usually been approved at doses near the top of their respective dose¿response curves. Efficacy plateaus but adverse drug reactions (ADRs), such as falls, cerebral or renal ischaemia, increase as dose is increased, especially in older patients with comorbidities. ADRs reduce adherence and may be difficult to ascertain reliably. Higher doses have generally not been shown to reduce total mortality, which provides a summary of efficacy and safety. Weight loss and other lifestyle measures are essential and may be sufficient treatment in many young and low risk patients. Most antihypertensive drug lower systolic blood pressure by around 10 mmHg, which reduces stroke and heart failure by about a quarter. Clinical trials have not been designed to demonstrate specific blood pressure treatment thresholds and targets, which are mostly extrapolated from epidemiology. Mean population oral effective dose 50 may be the most appropriate dose at which to commence antihypertensive drugs. The dose can then be titrated up if greater efficacy is demonstrated, or lowered if ADRs develop. Lower dose combination therapy may best balance benefit and harms with fewer ADRs and additive, potentially synergistic, efficacy.
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2019 |
O Hara K, Schneider JJ, Jones AL, Wright IMR, Martin JH, Galettis P, 'Development of an UHPLC-MS/MS method for remifentanil quantification in a small plasma volume', Journal of Liquid Chromatography and Related Technologies, 42 521-527 (2019) [C1] Remifentanil is a short acting opioid currently used in anesthesia and as an analgesic. This paper describes a simple, fast HPLC-MS/MS methodology that allows detection of remifen... [more] Remifentanil is a short acting opioid currently used in anesthesia and as an analgesic. This paper describes a simple, fast HPLC-MS/MS methodology that allows detection of remifentanil in low volume plasma samples. Acetonitrile protein precipitation is used for sample extraction and clean up. The assay has a lower limit of detection of 0.25 ng/mL and a 3 min run time.
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2019 |
Cirulli ET, Nicoletti P, Abramson K, Andrade RJ, Bjornsson ES, Chalasani N, et al., 'A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury', Gastroenterology, 156 1707-1716.e2 (2019) [C1] Background & Aims: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with s... [more] Background & Aims: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. Methods: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. Results: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28¿1.62; P = 1.2 × 10¿9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09¿1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32¿1.98; P = 4.0 × 10¿6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21¿1.56; P = 1.5 × 10¿6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
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2019 |
Falconer N, Barras M, Martin J, Cottrell N, 'Defining and classifying terminology for medication harm: a call for consensus', European Journal of Clinical Pharmacology, 75 137-145 (2019) [C1] Purpose: The multiplicity in terms and definitions of medication-related harm has been a long-standing challenge for health researchers, clinicians, and regulatory bodies. The pur... [more] Purpose: The multiplicity in terms and definitions of medication-related harm has been a long-standing challenge for health researchers, clinicians, and regulatory bodies. The purpose of this narrative review was to report the diversity of terms; compare definitions, classifications, and models describing medication harm; and suggest which may be useful in both clinical practice and the research setting. Methods: A narrative review of key studies defining and/or classifying medication harm terminology was undertaken. Results: This review found that numerous terms are used to describe medication harm, and that there is a lack of consistency in current definitions, classifications, and applications. This lack of consistency applied across clinical jurisdictions and regulatory terminologies. A number of limitations in current definitions and classifications were identified. These included the exclusion of key types of medication harm events, ambiguous wording, and a lack of clarity and consensus on subclassifications. In general, there was some overlap in key models from the literature and these were presented to describe similarities and differences. Conclusion: Without uniformity quantifying, comparing, combining, or extrapolating medication harm data, such as a rate of harm in a specific population, is a challenge for those involved in medication safety and pharmacovigilance. There is a pressing need for further discussion and international consensus on this topic. Adoption of standard descriptors by practitioner groups, regulatory and policy organisations would foster quality improvement and patient safety.
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2019 |
Hayward KL, Patel PJ, Valery PC, Horsfall LU, Li CY, Wright PL, et al., 'Medication-Related Problems in Outpatients With Decompensated Cirrhosis: Opportunities for Harm Prevention', HEPATOLOGY COMMUNICATIONS, 3 620-631 (2019) [C1]
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2019 |
Liu Z, Cheng J, Powell E, Macdonald G, Fawcett J, Lynch S, Martin J, 'Weight-based tacrolimus trough concentrations post liver transplant', Internal Medicine Journal, 49 79-83 (2019) [C1] Background: Tacrolimus is one of the most widely used liver transplant medications. With the increasing number of obese patients requiring liver transplants, knowledge of the effe... [more] Background: Tacrolimus is one of the most widely used liver transplant medications. With the increasing number of obese patients requiring liver transplants, knowledge of the effect of body size affecting post-transplant outcomes, for example drug exposure is increasingly required. Aims: (i) To investigate whether patient body size (i.e. total bodyweight) affects trough plasma concentrations of tacrolimus when a standard mg/kg dosing regimen is used; and (ii) to investigate whether obese patients have different numbers of plasma concentrations outside the therapeutic range compared to non-obese patients in the first months after liver transplant. Methods: Using a transplant database, data tacrolimus concentrations were available for 69 patients. Tacrolimus was initially dosed at a standard 0.1 mg/kg/day after liver transplant, and adjusted to maintain a target trough concentration. Trough blood samples, phenotypic and outcome variables were analysed. Results: Trough concentrations were similar between obese and non-obese patients (P > 0.05) at each sampling day. At day 7 post-transplant, 85.7% and 79.5% of the observed plasma concentrations were outside the recommended therapeutic range for obese and non-obese patients respectively, at day 30, 52.9% and 57.4%, and at 6 months, 18.7% and 27.5%. Conclusion: In the first week post-transplant, tacrolimus trough concentrations after standard mg/kg dosing post liver transplant appear to be corrected by total bodyweight. Obese patients have a similar number of trough plasma concentrations outside the therapeutic range compared to non-obese patients.
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2019 |
Williams M, Martin J, Galettis P, 'A validated method for the detection of synthetic cannabinoids in oral fluid', Journal of Analytical Toxicology, 43 10-17 (2019) [C1] Workplace drug testing in Australia is governed by two standards AS/NZS 4308:2008 for testing in urine and AS 4760:2006 for oral fluid. These standards are prescriptive and descri... [more] Workplace drug testing in Australia is governed by two standards AS/NZS 4308:2008 for testing in urine and AS 4760:2006 for oral fluid. These standards are prescriptive and describe the drugs tested, procedures for analysis and collection devices. However, the drugs listed are not exhaustive and workers may consume novel psychoactive substances without detection. Here we present a validated method for the detection and quantitation of 19 synthetic cannabinoids in oral fluid. These drugs are AM2233, JWH-200, AB-005, AB-FUBINACA, AB-PINACA, AB-CHMINACA, AM2201, RCS-4, JWH-250, STS-135, JWH-73, XLR-11, JWH-251, JWH-18, JWH-122, JWH-19, UR-144, JWH-20 and AKB-48. The sample volume is 100 µL and is subject to a rapid, simple, protein precipitation step prior to centrifugation and injection into the LC-MS/MS system. Chromatographic separation was achieved in 4 min on a Kinetex Biphenyl column (50 mm × 3 mm × 2.6 µm) using 0.1% formic acid in water and acetonitrile as the mobile phase. The method was validated with a limit of detection (1 ng/mL) limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (90.5-112.5% of the target concentration) and precision (3-14.7%). This method provides for the rapid detection of synthetic cannabinoids in oral fluid which is readily applicable to a routine laboratory.
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2019 |
Bernardes CM, Beesley V, Martin J, Sabesan S, Baade P, Meiklejohn JA, et al., 'Unmet supportive care needs among people with cancer: A cross-cultural comparison between Indigenous and Non-Indigenous Australians', EUROPEAN JOURNAL OF CANCER CARE, 28 (2019) [C1]
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2019 |
Lucas CJ, Dimmitt SB, Martin JH, 'Optimising low-dose methotrexate for rheumatoid arthritis A review', British Journal of Clinical Pharmacology, 85 2228-2234 (2019) [C1] Methotrexate at low doses (5¿25¿mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of va... [more] Methotrexate at low doses (5¿25¿mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of variability in concentrations of active polyglutamate metabolites, associated with clinical efficacy and toxicity. Prescribing remains heterogeneous across population groups, disease states and regimens. This review examines current knowledge of dose¿response of oral methotrexate in the setting of rheumatoid arthritis, and how this could help inform dosage regimens.
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2019 |
Martin JH, Dimmitt S, 'The rationale of dose response curves in selecting cancer drug dosing', British Journal of Clinical Pharmacology, 85 2198-2204 (2019) [C1] Drug development for cancer chemotherapy has an interesting history. A mix of serendipity, animal, cell line, and standard pharmacological principles of dose, dose-response, dose-... [more] Drug development for cancer chemotherapy has an interesting history. A mix of serendipity, animal, cell line, and standard pharmacological principles of dose, dose-response, dose-concentration, dose intensity and combination therapies have been used to develop optimal dosing schedules. However in practice, significant gaps in the translation of preclinical to clinical dosing schedules persist, and clinical development has instead moved to new drug development. A older chemotherapies are still the backbone of most solid tumour schedules, therapeutic drug monitoring has emerged as a method for optimising the dose for individual patients.
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2019 |
Frazer A, Rowland J, Mudge A, Barras M, Martin J, Donovan P, 'Systematic review of interventions to improve safety and quality of anticoagulant prescribing for therapeutic indications for hospital inpatients.', European journal of clinical pharmacology, 75 1645-1657 (2019) [C1]
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2019 |
Solowij N, Broyd S, Greenwood LM, van Hell H, Martelozzo D, Rueb K, et al., 'A randomised controlled trial of vaporised Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, ¿ 9 -tetrahydrocannabin... [more] Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, ¿ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400¿mg); THC alone (8¿mg) vs THC combined with low (4¿mg) or high (400¿mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p <.0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users. Trial registration: ISRCTN Registry Identifier: ISRCTN24109245.
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2018 |
Solowij N, Galettis P, Broyd SJ, de Krey P, Martin JH, 'Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to Patients in a Hospital Setting', Drugs in R and D, 18 41-44 (2018) [C1] Background: In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and s... [more] Background: In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and surrounding patients. Different modes of administration also provide different yet potentially significant issues. One route that has become of clinical interest owing to the rapid onset of action and patient control of the inhaled amount (via breath timing and depth) is that of vaporisation of cannabinoid products. Although requiring a registered therapeutic device for administration, this is a relatively safe method of intrapulmonary administration that may be particularly useful for patients with difficulty swallowing, and for those in whom higher concentrations of cannabinoids are needed quickly. A particular concern expressed to researchers undertaking clinical trials in the hospital is that other patients, nurses, and clinical or research staff may be exposed to second-hand vapours in the course of administering vaporised products to patients. Objective: The objective of this study was to take samples from two research staff involved in administering vaporised ¿9-tetrahydrocannabinol to participants in a clinical trial, to examine and quantitate cannabinoid presence. Methods: Blood samples from two research staff were taken during the exposure period for three participants (cannabis users) over the course of approximately 2.5¿h and analysed using tandem mass spectrometry. Results: Blood samples taken over a vaporised period revealed exposure below the limit of detection for ¿9-tetrahydrocannabinol and two metabolites, using tandem mass spectrometry analytical methods. Conclusions: These results are reassuring for hospital and clinical trial practices with staff administering vaporised cannabinoid products, and helpful to ethics committees wishing to quantify risk.
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2018 |
Bernardes CM, Martin J, Cole P, Kitchener T, Cowburn G, Garvey G, et al., 'Lessons learned from a pilot study of an Indigenous patient navigator intervention in Queensland, Australia', European Journal of Cancer Care, 27 (2018) [C1]
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2018 |
Martin JH, Schneider J, Lucas CJ, Galettis P, 'Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction?', Clinical Pharmacokinetics, 57 539-545 (2018) [C1] Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics r... [more] Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation. Significant recent interest has thus been shown in understanding these pathways to guide the development of agents that inhibit the natural catabolism of endogenous cannabinoids to modify pain and appetite, and to synthesise antagonists for the treatment of disease such as obesity. This research is concurrent with the renewed clinical interest in exogenous cannabinoids and their use in disease. However, the complex pharmacology and physiological effects of exogenous cannabinoids, either as individual components or in combination, as extracts or via administration of the whole plant in humans, are less well known. Yet as with all other therapeutics, including those derived from plants, knowledge of the pharmacokinetics and dynamics of the complete plant, the individual chemical molecules and their synthetic versions, including formulations and excipients is a standard part of drug development. This article covers the key pharmacological knowledge required to guide further exploration of the toxicity and efficacy of different cannabinoids and their formulations in blinded placebo-controlled studies.
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2018 |
He W, Martin JH, Shaw PN, Lu X, Walpole ET, Dimeski G, 'A Simple and Sensitive LC-MS/MS Method for the Simultaneous Determination of Cyclophosphamide and Dexorubicin Concentrations in Human Plasma', CURRENT PHARMACEUTICAL ANALYSIS, 14 53-59 (2018) [C1]
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2018 |
Solowij N, Broyd SJ, Beale C, Prick J-A, Greenwood L-M, van Hell H, et al., 'Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.', Cannabis Cannabinoid Res, 3 21-34 (2018) [C1]
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2018 |
Liu Z, Martin JH, 'Gaps in predicting clinical doses for cannabinoids therapy: Overview of issues for pharmacokinetics and pharmacodynamics modelling.', British journal of clinical pharmacology, 84 2483-2487 (2018) [C1]
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2018 |
McGee M, Whitehead N, Martin J, Collins N, 'Drug-associated pulmonary arterial hypertension.', Clinical toxicology (Philadelphia, Pa.), 56 801-809 (2018) [C1]
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2018 |
Tam L, Garvey G, Meiklejohn J, Martin J, Adams J, Walpole E, et al., 'Exploring positive survivorship experiences of indigenous Australian cancer patients', International Journal of Environmental Research and Public Health, 15 (2018) [C1]
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2018 |
Patel J, Lucas CJ, Margalit M, Martin JH, 'Laxative Use in Inpatients on Oxycodone/Naloxone Prolonged Release and Oxycodone Prolonged Release for Cancer and Non-cancer Pain', Journal of Pain and Palliative Care Pharmacotherapy, 32 116-123 (2018) [C1] Objective: To examine the laxative prescriptions in hospital inpatients with cancer and non-cancer pain on oxycodone compared to oxycodone plus naloxone combination. Design: Retro... [more] Objective: To examine the laxative prescriptions in hospital inpatients with cancer and non-cancer pain on oxycodone compared to oxycodone plus naloxone combination. Design: Retrospective case note review. Setting: A palliative care inpatient unit and a general medical ward in a large tertiary referral hospital. Participants: Eighty-four patients receiving oxycodone or combination oxycodone/naloxone on general medical (45 patients) and palliative care wards (39 patients). Main outcome measures: The primary recorded outcomes were regular opioid dose (milligrams per day) and number of prescribed laxatives (type, doses, and frequency per day). Results: Sixty-three (75%) patients in the study were on at least one laxative. In the general medicine inpatients, those on combined oxycodone/naloxone received on average 3.7 laxative doses per day compared to the oxycodone patients receiving 1.6 doses a day. In the palliative medicine population, both groups received a similar number of laxatives, despite the oxycodone/naloxone patients being on lower opioid doses. Conclusion: This retrospective study of hospital inpatients with cancer and non-cancer pain found that laxative use was not reduced in those on combined oxycodone/naloxone compared to oxycodone alone, suggesting that despite the interpretations of the clinical trials in the phase IV setting, the addition of naloxone had no effect on reducing laxative use.
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2018 |
Linger M, Martin J, 'Pharmacovigilance and expedited drug approvals.', Australian prescriber, 41 50-53 (2018) [C1]
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2018 |
Beale C, Broyd SJ, Chye Y, Suo C, Schira M, Galettis P, et al., 'Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.', Cannabis and cannabinoid research, 3 94-107 (2018) [C1]
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2018 |
Meiklejohn JA, Arley B, Bailie R, Adams J, Garvey G, Martin JH, et al., 'Community-identified recommendations to enhance cancer survivorship for Aboriginal and Torres Strait Islander people', Australian Journal of Primary Health, 24 233-240 (2018) [C1] Indigenous Australians diagnosed with cancer experience higher mortality and lower survival rates compared to non-Indigenous Australians. Reasons are multifaceted and complex. Kno... [more] Indigenous Australians diagnosed with cancer experience higher mortality and lower survival rates compared to non-Indigenous Australians. Reasons are multifaceted and complex. Knowledge about Indigenous cancer survivors' perspectives of positive cancer survivorship is a gap in research evidence. The study explored cancer survivorship perspectives of Indigenous cancer survivors, their support people and healthcare workers with a view to developing recommendations for cancer survivorship. Indigenous Australians who completed cancer treatment in the previous 6 months to 5 years, their support people and primary healthcare workers were recruited from primary healthcare centres and a large tertiary Queensland hospital. Semi-structured interviews and focus groups were conducted with written and informed consent obtained prior. Participants emphasised key action areas and recommendations to enhance cancer survivorship, namely: establishing a community cancer advocate and peer support program, availability and use of a cancer-specific Indigenous primary healthcare worker and hospital-based Indigenous patient navigator, as well as adoption of question prompt lists and cancer survivorship care plans. Existing research suggests significant benefits from implementing the key recommendations identified in this study. Greater support and commitment across health sectors and funding bodies is needed to promote institutional change and health system development.
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2018 |
Martin JH, Bonomo Y, Reynolds ADB, 'Compassion and evidence in prescribing cannabinoids: a perspective from the Royal Australasian College of Physicians', Medical Journal of Australia, 208 107-109 (2018) [C1]
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2018 |
Liu Z, Martin J, Orme L, Seddon B, Desai J, Nicholls W, et al., 'Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood', Cancer Chemotherapy and Pharmacology, 82 887-898 (2018) [C1]
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2018 |
Martin J, Linger M, 'Automated adverse drug reaction detection', AUSTRALIAN PRESCRIBER, 41 138-138 (2018)
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2018 |
Dryburgh LM, Bolan NS, Grof CPL, Galettis P, Schneider J, Lucas CJ, Martin JH, 'Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects.', British journal of clinical pharmacology, 84 2468-2476 (2018) [C1]
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2017 |
Lucas CJ, Patel J, Martin JH, 'Predicting drug interactions in addiction treatment', Internal Medicine Journal, 47 872-878 (2017) [C1] It is not uncommon to be treating people with addiction who also have significant other health problems, including heart, renal or liver failure, diabetes and vascular disease. Th... [more] It is not uncommon to be treating people with addiction who also have significant other health problems, including heart, renal or liver failure, diabetes and vascular disease. These conditions require regular medications to be taken. This can be a problem for people living with addiction and difficult social circumstances affecting compliance, among other issues. Our perspective provides a summary of general pharmacological factors affecting medicine taking in people with addiction problems, to provide a guide for hospital doctors in this setting.
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2017 |
'Hepatology Clinical', Journal of Gastroenterology and Hepatology, 32 87-115 (2017)
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2017 |
Valery PC, Clark PJ, McPhail SM, Rahman T, Hayward K, Martin J, et al., 'Exploratory study into the unmet supportive needs of people diagnosed with cirrhosis in Queensland, Australia', INTERNAL MEDICINE JOURNAL, 47 429-435 (2017) [C1]
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2017 |
Meiklejohn JA, Garvey G, Bailie R, Walpole E, Adams J, Williamson D, et al., 'Follow-up cancer care: perspectives of Aboriginal and Torres Strait Islander cancer survivors', Supportive Care in Cancer, 25 1597-1605 (2017) [C1] Purpose: The purpose of this study was to explore Indigenous Australian cancer survivors¿ perspectives of follow-up cancer care and management. Methods: This is a qualitative stud... [more] Purpose: The purpose of this study was to explore Indigenous Australian cancer survivors¿ perspectives of follow-up cancer care and management. Methods: This is a qualitative study employing individual interviews with 21 Indigenous cancer survivors (13 females, 8 males) recruited from a rural primary health service and large tertiary hospital in Brisbane, Queensland. Yarning methods were used to conduct semi-structured interviews. Yarning is a culturally appropriate, informal conversational process emphasising the importance of storytelling. Results: Findings describe a range of ways in which follow-up cancer care is experienced with four major categories elucidated, namely: links to tertiary health services, links to primary health services, communication between tertiary and primary health services, and lost in transition. Both positive and negative experiences were described; however, the importance of timely and informative discharge information, continuity of care, good communication between tertiary and primary health services, and strong therapeutic relationships were salient issues raised by participants. Conclusions: These findings highlight the importance of establishing strong therapeutic relationships between patients and tertiary and primary health professionals. Also important for survivorship is provision of discharge summaries or care plans at discharge for survivors and general practitioners as well as access to a range of allied health services. Alternative means for follow-up could be investigated for regional and rural survivors to facilitate convenient and cost-effective follow-up care. Finally, provision of responsive and flexible follow-up care to cater for the diverse range of needs and preferences of cancer survivors is required. A patient navigator available across the cancer continuum could go some way to addressing this.
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2017 |
Hayward KL, Horsfall LU, Ruffin BJ, Cottrell WN, Chachay VS, Irvine KM, et al., 'Optimising care of patients with chronic disease: patient-oriented education may improve disease knowledge and self-management', Internal Medicine Journal, 47 952-955 (2017) [C1]
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2017 |
Dimmitt SB, Martin JH, 'Lipid and other management to improve arterial disease and survival in end stage renal disease', Expert Opinion on Pharmacotherapy, 18 343-349 (2017) [C1] Introduction: Arterial disease is common in advancing renal failure, culminating in myocardial infarction with cardiac failure, strokes and peripheral and renal artery disease. At... [more] Introduction: Arterial disease is common in advancing renal failure, culminating in myocardial infarction with cardiac failure, strokes and peripheral and renal artery disease. Attention to cardiac and arterial disease may slow deterioration of renal function. Management of risk factors can reduce these sequelae. Areas covered: Modifiable risk factors for arterial disease and relevant pharmacotherapies. Expert opinion: Cardiovascular disease is the biggest killer in renal failure. Statins are viewed as essential in symptomatic coronary disease and have been shown in non-renal patients to improve survival after myocardial infarction. Cochrane recommends statins in renal failure but not in end stage renal disease or transplant patients. Large well powered clinical trials focussed specifically on renal patients failed to demonstrate cardiovascular outcome or mortality benefits of statins when compared to placebo. Other lipid lowering pharmacotherapies are weaker and adverse effects may account for the absence of net clinical benefit in non-renal patients in published clinical trials. Patients should be started on a statin after myocardial infarction, regardless of lipid levels, but the risk of adverse effects in advanced renal failure with its comorbidities predicates employing only essential doses. Optimal antihypertensive and antithrombotic pharmacotherapy are also priorities.
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2017 |
Hollingworth SA, Ostino R, David MC, Martin JH, Tett SE, 'Ezetimibe: Use, costs, and adverse events in Australia', Cardiovascular Therapeutics, 35 40-46 (2017) [C1]
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2017 |
Head RJ, Fay MF, Cosgrove L, Y C Fung K, Rundle-Thiele D, Martin JH, 'Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma', Cancer Biology and Therapy, 18 917-926 (2017) [C1] Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this m... [more] Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O6-methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.
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2017 |
de Witt A, Cunningham FC, Bailie R, Bernardes CM, Matthews V, Arley B, et al., 'Identification of Australian Aboriginal and Torres Strait Islander Cancer Patients in the Primary Health Care Setting', FRONTIERS IN PUBLIC HEALTH, 5 1-8 (2017) [C1]
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2017 |
Hayward KL, Valery PC, Martin JH, Karmakar A, Patel PJ, Horsfall LU, et al., 'Medication beliefs predict medication adherence in ambulatory patients with decompensated cirrhosis', World Journal of Gastroenterology, 23 7321-7331 (2017) [C1] Aim: To investigate the impact of medication beliefs, illness perceptions and quality of life on medication adherence in people with decompensated cirrhosis. Methods: One hundred ... [more] Aim: To investigate the impact of medication beliefs, illness perceptions and quality of life on medication adherence in people with decompensated cirrhosis. Methods: One hundred adults with decompensated cirrhosis completed a structured questionnaire when they attended for routine outpatient hepatology review. Measures of self-reported medication adherence (Morisky Medication Adherence Scale), beliefs surrounding medications (Beliefs about Medicines Questionnaire), perceptions of illness and medicines (Brief Illness Perception Questionnaire), and quality of life (Chronic Liver Disease Questionnaire) were examined. Clinical data were obtained via patient history and review of medical records. Least absolute shrinkage and selection operator and stepwise backwards regression techniques were used to construct the multivariable logistic regression model. Statistical significance was set at alpha = 0.05. Results: Medicat ion adherence was "High" in 42% of participants, "Medium" in 37%, and "Low" in 21%. Compared to patients with "High" adherence, those with "Medium" or "Low" adherence were more likely to report difficulty affording their medications (P < 0.001), lower perception of treatment helpfulness (P = 0.003) and stronger medication concerns relative to medication necessity beliefs (P = 0.003). People with "Low" adherence also experienced greater symptom burden and poorer quality of life, including more frequent abdominal pain (P = 0.023), shortness of breath (P = 0.030), and emotional disturbances (P = 0.050). Multivariable analysis identified having stronger medication concerns relative to necessity beliefs (Necessity-Concerns Differential = 5, OR = 3.66, 95%CI: 1.18-11.40) and more frequent shortness of breath (shortness of breath score = 3, OR = 3.87, 95%CI: 1.22-12.25) as independent predictors of "Low" adherence. Conclusion: The association between "Low" adherence and patients having strong concerns or doubting the necessity or helpfulness of their medications should be explored further given the clinical relevance.
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2017 |
Williams M, Martin J, Galettis P, 'A validated method for the detection of 32 bath salts in oral fluid', Journal of Analytical Toxicology, 41 659-669 (2017) [C1] Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tes... [more] Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tested, devices used and testing methodology followed by the testing agency. However, they are not comprehensive and for many years workers have been able to consume novel psychoactive substances to avoid detection and without consequences. Here, we present a validated method for the detection of 32 Synthetic Stimulant and Hallucogenic drugs, commonly sold as bath salts, in oral fluid. These drugs are cathinone, ephedrone, methylone, flephedrone, MDA, PMA, methedrone, TMA, MDMA, butylone, mephedrone, MDEA, MEC, pentedrone, MBDB, MTA, Alpha-PVP, MPBP, 2C-B, MDPV, DOB, 2C-T-2, TFMPP, DOET, 2C-T-7, naphyrone, MDAI, FMA, DMA, 25C-NBOMe, 25B-NBOMe and 25T4-NBOMe. Sample preparation was undertaken using a simple protein precipitation in acetonitrile. Chromatographic separation was achieved in 7.5 min on a Kinetex F5 column (50mm × 3mm × 2.6 µm) using 0.1% formic acid in water and acetonitrile as the mobile phases. The method was validated with limit of detection (1 ng/mL), limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (85.3-108.4% of the target concentration) and precision (1.9-14%). This method was applied to 12 samples previously submitted for routine testing and two were found to contain 2-CB and DOB (5 and 4 ng/mL) and, MPBP and TFMPP (both at 4 ng/mL). This method provides for the rapid detection of a large number of compounds in oral fluid which is readily applicable to routine testing laboratories.
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2017 |
Donagher J, Martin JH, Barras MA, 'Individualised medicine: why we need Bayesian dosing.', Intern Med J, 47 593-600 (2017) [C1]
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2017 |
Dimmitt S, Stampfer H, Martin JH, 'When less is more efficacy with less toxicity at the ED50', British Journal of Clinical Pharmacology, 83 1365-1368 (2017) [C1]
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2017 |
Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, et al., 'Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study', Gastroenterology, 152 1078-1089 (2017) [C1]
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2017 |
Kim HY, Martin JH, Mclachlan AJ, Boddy AV, 'Precision dosing of targeted anticancer drugs-challenges in the real world', Translational Cancer Research, 6 S1500-S1511 (2017) [C1] The prerequisites for the successful implementation of therapeutic drug monitoring (TDM) include high inter-subject variation, low inter-occasion variation, narrow therapeutic ind... [more] The prerequisites for the successful implementation of therapeutic drug monitoring (TDM) include high inter-subject variation, low inter-occasion variation, narrow therapeutic index and a strong link between plasma drug concentrations and clinical effects. The degree to which targeted anticancer drugs meet these criteria is not the only consideration in implementing precision dosing. Methodological, logistical, funding and cultural barriers also provide challenges to the successful implementation of approaches to individualised therapy. This review considers the barriers to the routine use of TDM, using examples from both conventional (cytotoxic) anticancer, but also considering more recent data and examples more relevant to chronic, oral administration of targeted therapies. Based on these examples and the associated principles for the implementation of precision dosing, proposals may be made for a more rational, real-world approach to the best use of precision medicines.
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2017 |
Mitrev N, Vande Casteele N, Seow CH, Andrews JM, Connor SJ, Moore GT, et al., 'Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.', Alimentary pharmacology & therapeutics, 46 137-143 (2017) [C1]
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2017 |
Lucas CJ, Martin JH, 'Pharmacokinetic-Guided Dosing of New Oral Cancer Agents', Journal of Clinical Pharmacology, 57 S78-S98 (2017) [C1] Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-age... [more] Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese¿even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area¿guided dosing, therapeutic drug monitoring or pharmacokinetic-guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size¿based dosing or ¿one dose fits all¿ is used. This review will focus predominantly on the rationale for pharmacokinetic-guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.
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2016 |
Luckett T, Phillips J, Lintzeris N, Allsop D, Lee J, Solowij N, et al., 'Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation', Internal Medicine Journal, 46 1269-1275 (2016) [C1] Background: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. Aims: To explore the preferences, attitudes and beliefs of patie... [more] Background: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. Aims: To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer. Methods: A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were =18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns. Results: There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial. Conclusion: Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.
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2016 |
Skinner TR, Scott IA, Martin JH, 'Diagnostic errors in older patients: A systematic review of incidence and potential causes in seven prevalent diseases', International Journal of General Medicine, 9 137-146 (2016) [C1] Background: Misdiagnosis, either over-or underdiagnosis, exposes older patients to increased risk of inappropriate or omitted investigations and treatments, psychological distress... [more] Background: Misdiagnosis, either over-or underdiagnosis, exposes older patients to increased risk of inappropriate or omitted investigations and treatments, psychological distress, and financial burden. Objective: To evaluate the frequency and nature of diagnostic errors in 16 conditions prevalent in older patients by undertaking a systematic literature review. Data sources and study selection: Cohort studies, cross-sectional studies, or systematic reviews of such studies published in Medline between September 1993 and May 2014 were searched using key search terms of ¿diagnostic error¿, ¿misdiagnosis¿, ¿accuracy¿, ¿validity¿, or ¿diagnosis¿ and terms relating to each disease. Data synthesis: A total of 938 articles were retrieved. Diagnostic error rates of >10% for both over-and underdiagnosis were seen in chronic obstructive pulmonary disease, dementia, Parkinson¿s disease, heart failure, stroke/transient ischemic attack, and acute myocardial infarction. Diabetes was overdiagnosed in <5% of cases. Conclusion: Over-and underdiagnosis are common in older patients. Explanations for overdiagnosis include subjective diagnostic criteria and the use of criteria not validated in older patients. Underdiagnosis was associated with long preclinical phases of disease or lack of sensitive diagnostic criteria. Factors that predispose to misdiagnosis in older patients must be emphasized in education and clinical guidelines.
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2016 |
Meiklejohn JA, Mimery A, Martin JH, Bailie R, Garvey G, Walpole ET, et al., 'The role of the GP in follow-up cancer care: a systematic literature review', Journal of Cancer Survivorship, 10 990-1011 (2016) [C1] Purpose: The purpose of the present study is to explore the role of the general practitioners, family physicians and primary care physicians (GP) in the provision of follow-up can... [more] Purpose: The purpose of the present study is to explore the role of the general practitioners, family physicians and primary care physicians (GP) in the provision of follow-up cancer care. Methods: PubMed, MEDLINE and CINAHL were systematically searched for primary research focussing on the role of the GP from the perspective of GPs and patients. Data were extracted using a standardised form and synthesised using a qualitative descriptive approach. Results: The initial search generated 6487 articles: 25 quantitative and 33 qualitative articles were included. Articles focused on patients¿ and GPs¿ perspectives of the GP role in follow-up cancer care. Some studies reported on the current role of the GP, barriers and enablers to GP involvement from the perspective of the GP and suggestions for future GP roles. Variations in guidelines and practice of follow-up cancer care in the primary health care sector exist. However, GPs and patients across the included studies supported a greater GP role in follow-up cancer care. This included greater support for care coordination, screening, diagnosis and management of physical and psychological effects of cancer and its treatment, symptom and pain relief, health promotion, palliative care and continuing normal general health care provision. Conclusion: While there are variations in guidelines and practice of follow-up cancer care in the primary health care sector, GPs and patients across the reviewed studies supported a greater role by the GP. Implications for Cancer Survivors: Greater GP role in cancer care could improve the quality of patient care for cancer survivors. Better communication between the tertiary sector and GP across the cancer phases would enable clear delineation of roles.
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2016 |
Lucas C, Byles J, Martin JH, 'Medicines optimisation in older people: Taking age and sex into account', Maturitas, 93 114-120 (2016) [C1] There are a number of complex and seemingly ignored issues around prescribing safely and effectively for older people, particularly for very old women. These issues include polyph... [more] There are a number of complex and seemingly ignored issues around prescribing safely and effectively for older people, particularly for very old women. These issues include polypharmacy, possible compliance issues and communication barriers between patient, specialists and general practitioners (GPs). There are specific pharmacokinetic (PK) and pharmacodynamic (PD) parameters that change in older age generally, and in women more specifically, which if ignored are likely to cause symptoms and to impair quality of life when drug dosage is unchanged. These changed PK and PD parameters are not all-or-nothing processes, but a continuum across age, sex and comorbidity. Very old people also have less ¿reserve¿ when drugs are used in ¿standard' doses, are more likely to have multiple concurrent therapies, and the risk of adverse effects of drugs in this group is very high. Doctors need to consider these issues when providing therapy for this group, or when trying to unravel the complex prescribing cascade here. This review outlines general principles to consider when prescribing for older people, focusing on age- and sex-related changes in both PK and PD processes.
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2016 |
Meiklejohn JA, Adams J, Valery PC, Walpole ET, Martin JH, Williams HM, Garvey G, 'Health professional's perspectives of the barriers and enablers to cancer care for Indigenous Australians', European Journal of Cancer Care, 25 254-261 (2016) [C1] To investigate health professionals' perspectives about factors that impede or facilitate cancer care for Indigenous people. Semi-structured interviews with 22 health profess... [more] To investigate health professionals' perspectives about factors that impede or facilitate cancer care for Indigenous people. Semi-structured interviews with 22 health professionals involved in Indigenous cancer care. Data were interpreted using an inductive thematic analysis approach. Participants presented their perspectives on a number of barriers and enablers to Indigenous cancer care. Barriers were related to challenges with communication, the health system and coordination of care, issues around individual and community priorities and views of cancer treatment and health professional judgement. Enablers to cancer care were related to the importance of trust and rapport as well as health care system and support factors. The findings highlighted the need for recording of Indigenous status in medical records and a coordinated approach to the provision of evidence-based and culturally appropriate cancer care. This could go some way to improving Indigenous patient's engagement with tertiary cancer care services.
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2016 |
Linger MW, van Driel ML, Hollingworth SA, Martin JH, 'Off-label use of tumour necrosis factor-alpha inhibitors and anakinra at an Australian tertiary hospital', Internal Medicine Journal, 46 1386-1391 (2016) [C1] Background: Tumour necrosis factor-alpha inhibitors (anti-TNFa) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammato... [more] Background: Tumour necrosis factor-alpha inhibitors (anti-TNFa) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammatory diseases. In Australia, they are registered for the treatment of several rheumatological, gastroenterological and dermatological indications. Despite increasing observational evidence for their use in off-label indications, there is a paucity of outcome research from the Australian hospital sector. Aims: To describe the off-label use of anti-TNFa and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making. Methods: We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFa or anakinra at the Royal Brisbane and Women's Hospital from mid-2010 to mid-2014, linking demographic, phenotypic, pathology and outcome data with these drugs. Results: Off-label use was identified in 10 patients. The most frequent indications were sarcoidosis and dermatological conditions. Three patients required sequential therapy with a second anti-TNFa (total responses = 13). Complete response occurred in 46%, partial response in 38% and primary non-response in 8%. Response was unable to be determined in 8%. We recorded 14 adverse events (infections most common). Conclusion: This study suggests that anti-TNFa may be beneficial for some off-label indications (e.g. sarcoidosis). However, the observational design of this study (and pre-existing research) limits the ability to infer causality and generalise results. We propose the creation of a mandatory drug register to monitor off-label use. Whilst comparative efficacy cannot be established without a matched placebo arm, a register would enable some reporting on effectiveness in rare diseases and identify infrequent but serious adverse events.
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2016 |
McDougall DAJ, Martin J, Playford EG, Green B, 'Determination of a suitable voriconazole pharmacokinetic model for personalised dosing', Journal of Pharmacokinetics and Pharmacodynamics, 43 165-177 (2016) [C1] Model based personalised dosing (MBPD) is a sophisticated form of individualised therapy, where a population pharmacokinetic (PK) or pharmacodynamic model is utilised to estimate ... [more] Model based personalised dosing (MBPD) is a sophisticated form of individualised therapy, where a population pharmacokinetic (PK) or pharmacodynamic model is utilised to estimate the dose required to reach a target exposure or effect. The choice of which model to implement in MBPD is a subjective decision. By choosing one model, information from the remaining models is ignored, as well as the rest of the literature base. This manuscript describes a methodology to develop a ¿hybrid¿ model for voriconazole that incorporated information from prior models in a biologically plausible manner. Voriconazole is a triazole antifungal with difficult to predict PK, although it does have a defined exposure¿response relationship. Nine population PK models of voriconazole were identified from the literature. The models differed significantly in structural components. The hybrid model contained a two-compartment disposition model with mixed linear and nonlinear time-dependent clearance. The parameters for the hybrid model were determined using simulation techniques. Validation of the hybrid model was assessed via visual predictive checks, which indicated the majority of the variability in the literature models was captured by the hybrid model. The predictive performance was assessed using four different sampling strategies of limited concentrations from ten richly PK sampled subjects to predict future concentrations. Overall, the hybrid model predicted future concentrations with good precision. Further prospective and retrospective validation of the hybrid model is required before it could be used in clinical practice.
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2016 |
Martin JH, Henry D, Gray J, Day R, Bochner F, Ferro A, et al., 'Achieving the World Health Organization's vision for clinical pharmacology.', Br J Clin Pharmacol, 81 223-227 (2016) [C1]
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2016 |
Moore SP, Soerjomataram I, Green AC, Garvey G, Martin J, Valery PC, 'Breast cancer diagnosis, patterns of care and burden of disease in Queensland, Australia (1998 2004): does being Indigenous make a difference?', International Journal of Public Health, 61 435-442 (2016) [C1] Objectives: We compared patterns of care, comorbidity, disability-adjusted life-years (DALYs) and survival in Indigenous and non-Indigenous women with breast cancer in Queensland,... [more] Objectives: We compared patterns of care, comorbidity, disability-adjusted life-years (DALYs) and survival in Indigenous and non-Indigenous women with breast cancer in Queensland, Australia (1998¿2004). Methods: A cohort study of Indigenous (n¿=¿110) and non-Indigenous women (n¿=¿105), frequency matched on age and remoteness. We used Pearson¿s Chi-squared analysis to compare proportions, hazard models to assess survival differences and calculated disability-adjusted life years (DALYs). Results: Indigenous women were more likely to be socially disadvantaged (43 vs. 20¿%, p¿<¿0.01) have comorbidity (42 vs. 18¿% p¿<¿0.01), and have regional spread or distant metastasis (metastasis, 51 vs. 36¿%, p¿=¿0.02) than non-Indigenous women; there was no difference in treatment patterns. More Indigenous women died in the follow-up period (p¿=¿0.01). DALY¿s were 469 and 665 per 100,000 for Indigenous and non-Indigenous women, respectively, with a larger proportion of the burden attributed to premature death among the former (63 vs. 59¿%). Conclusions: Indigenous women with breast cancer received comparable treatment to their non-Indigenous counterparts. The higher proportion of DALYs related to early death in Indigenous women suggests higher fatality with breast cancer in this group. Later stage at diagnosis and higher comorbidity presence among Indigenous women reinforce the need for early detection and improved management of co-existing disease.
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2016 |
McDougall DAJ, Martin J, Playford EG, Green B, 'The Impact of Model-Misspecification on Model Based Personalised Dosing', AAPS Journal, 18 1244-1253 (2016) [C1] Model Based Personalised Dosing (MBPD) requires a population pharmacokinetic (PK) or pharmacodynamic model to determine the optimal dose of medication for an individual. Often sev... [more] Model Based Personalised Dosing (MBPD) requires a population pharmacokinetic (PK) or pharmacodynamic model to determine the optimal dose of medication for an individual. Often several models are published, and the decision of which model is implemented in MBPD may have a large impact on its clinical utility. As quoted by Box, ¿all models are wrong, the practical question is how wrong can they be and still be useful¿. Voriconzole, a triazole antifungal and the example used in this manuscript, currently has nine population PK models published. To assess the impact of model-misspecification on MBPD, five structurally mis-specified models for voriconazole were developed. Intensive plasma concentrations were simulated for 100 virtual subjects. The dose adjustments required to reach a target exposure were determined by using the empirical Bayes estimates of the PK parameters under each of the mis-specified models. The predicted plasma concentrations and the probability of clinical outcomes, upon following the dose recommendations, were determined. Models that did not contain non-linear clearance performed poorly, with a median dose recommendation 155¿310¿mg higher than appropriate doses, when only one plasma concentration was available. Removal of body weight and CYP2C9 genotype as covariates had no clinically significant impact on outcomes. In summary, the removal of important structural components, such as non-linear clearance in the case of voriconazole, had a large impact on the clinical utility of MBPD. The removal of patient covariates, even highly influential covariates such as CYP2C9 genotype for voriconazole, had no clinical impact.
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2016 |
Garvey G, Cunningham J, He VY, Janda M, Baade P, Sabesan S, et al., 'Health-related quality of life among Indigenous Australians diagnosed with cancer', QUALITY OF LIFE RESEARCH, 25 1999-2008 (2016) [C1]
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2016 |
Petrie S, Barras M, Lust K, Fagermo N, Allen J, Martin JH, 'Evaluation of therapeutic enoxaparin in a pregnant population at a tertiary hospital', Internal Medicine Journal, 46 826-833 (2016) [C1] Background: Therapeutic anticoagulation with enoxaparin in pregnancy is complex due to varying pharmacokinetics and the increasing prevalence of obesity. There is limited evidence... [more] Background: Therapeutic anticoagulation with enoxaparin in pregnancy is complex due to varying pharmacokinetics and the increasing prevalence of obesity. There is limited evidence to support current dosing and monitoring strategies of enoxaparin in this population. Aim: To describe the current practice in therapeutic anticoagulation in the pregnant population at a tertiary institution. Methods: A retrospective study of pregnant women on therapeutic enoxaparin between January 2007 and December 2011. Results: Forty-four pregnant women requiring therapeutic anticoagulation were identified and divided into two groups, monitored with anti-factor Xa (AXA) concentrations and unmonitored. Fifty-five percent of monitored women were initiated on the recommended 1 mg/kg twice a day (bd) enoxaparin dose-strategy. Eighty-two percent of women were monitored; however, there was variability regarding the timing, frequency and subsequent dose adjustments from monitoring. Overall, as pregnancies progressed, there was both increasing dose adjustments and increasing frequency of monitoring. Fourteen women had a BMI over 30 kg/m2, and 13 of these women were monitored. Nine monitored obese women required doses less than 1 mg/kg/bd to maintain a therapeutic AXA level. Management appeared to be individualised. There were small numbers of toxicity events. Conclusion: Variation exists in dosing and monitoring practices for therapeutic enoxaparin in the pregnant population. Dosing obese patients using 1 mg/kg twice daily can lead to toxic AXA concentrations, and dose reductions are required to maintain a therapeutic range. A larger prospective study reviewing dose, AXA concentrations and outcome data is necessary to make dosing recommendations in this group.
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2016 |
Martin J, Bonomo YA, 'Medicinal cannabis in Australia: the missing links', MEDICAL JOURNAL OF AUSTRALIA, 204 371-373 (2016) [C1]
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2016 |
Hayward KL, Valery PC, Cottrell WN, Irvine KM, Horsfall LU, Tallis CJ, et al., 'Prevalence of medication discrepancies in patients with cirrhosis: a pilot study.', BMC gastroenterology, 16 114 (2016) [C1]
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2016 |
Rundle-Thiele D, Head R, Cosgrove L, Martin JH, 'Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma', British Journal of Clinical Pharmacology, 81 199-209 (2016) [C1] Glioblastoma is a brain neoplasm with limited 5-year survival rates. Developments of new treatment regimens that improve patient survival in patients with glioblastoma are needed.... [more] Glioblastoma is a brain neoplasm with limited 5-year survival rates. Developments of new treatment regimens that improve patient survival in patients with glioblastoma are needed. It is likely that a number of existing drugs used in other conditions have potential anticancer effects that offer significant survival benefit to glioblastoma patients. Identification of such drugs could provide a novel treatment paradigm.
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2016 |
Hayward KL, Powell EE, Irvine KM, Martin JH, 'Can paracetamol (acetaminophen) be administered to patients with liver impairment?', British Journal of Clinical Pharmacology, 81 210-222 (2016) [C1] Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulmin... [more] Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed.
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2016 |
Goulooze SC, Galettis P, Boddy AV, Martin JH, 'Monte Carlo simulations of the clinical benefits from therapeutic drug monitoring of sunitinib in patients with gastrointestinal stromal tumours', CANCER CHEMOTHERAPY AND PHARMACOLOGY, 78 209-216 (2016) [C1]
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2016 |
Ward MB, Reuter SE, Martin JH, 'How Optimal are Optimal Sampling Times for Tyrosine Kinase Inhibitors in Cancer? Practical Considerations', Clinical Pharmacokinetics, 55 1171-1177 (2016) [C1] Tyrosine kinase inhibitors have been marketed as a fixed dose, ¿one size fits all¿ treatment strategy. Physicians have also been interested in this method of dosing, knowing the c... [more] Tyrosine kinase inhibitors have been marketed as a fixed dose, ¿one size fits all¿ treatment strategy. Physicians have also been interested in this method of dosing, knowing the complex planning of other current cancer therapies administered on a mg/m2 or mg/kg basis and subsequent occurrence of dosing error or concern for underdosing. The ¿simple and safe¿ strategy of a single dose of tyrosine kinase inhibitor for cancer has thus been widely adopted. However, the benefits purported to exist in the clinical trials do not appear to be borne out in clinical practice, particularly in solid tumours. In order to investigate whether pharmacokinetic variability is a contributor to the variable outcomes, pharmacokinetic targets to enable individualisation of tyrosine kinase inhibitor administration are now emerging. Evidence suggests there is not a clear relationship of a single dose to maximum plasma concentration (Cmax), steady-state trough concentration (Ctrough) or area under the curve (AUC). Furthermore, a significant number of questions remain related to the specific timing and frequency of sample collection required to achieve optimal outcomes. This article reviews the wide variability in the literature on this topic, specifically the different pharmacokinetic targets of the same drug for different cancers, for different states of cancer, and changing pharmacokinetic parameters over a treatment interval in cancer. It appears the optimal sampling times to enable appropriate dose recommendations across patients and diseases may vary, and are not always trough concentrations at steady state. Importantly, the need to be pragmatic in a clinical setting is paramount. Lastly, international collaborations to increase sample size are highly recommended to ensure enough patients are sampled to be sure of a clinical benefit from this concentration-directed methodology.
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2016 |
Leung J, Martin J, McLaughlin D, 'Rural-urban disparities in stage of breast cancer at diagnosis in Australian women', The Australian journal of rural health, 24 326-332 (2016) [C1] OBJECTIVE: To examine urban-rural differences and individual risk factors for a late stage of breast cancer at diagnosis in Australian women.... [more] OBJECTIVE: To examine urban-rural differences and individual risk factors for a late stage of breast cancer at diagnosis in Australian women.
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2016 |
Reuter SE, Martin JH, 'Pharmacokinetics of Cannabis in Cancer Cachexia-Anorexia Syndrome', Clinical Pharmacokinetics, 55 807-812 (2016) [C1] Anorexia can affect up to 90¿% of people with advanced cancer. It is a complex symptom associated with changes in taste, lack of hunger at mealtimes and lack of food enjoyment. As... [more] Anorexia can affect up to 90¿% of people with advanced cancer. It is a complex symptom associated with changes in taste, lack of hunger at mealtimes and lack of food enjoyment. Associated weight loss is part of the physical decline that occurs as cancer worsens. Weight loss can also occur from cachexia, the increased metabolism of energy due to raised inflammatory cytokines, liver metastases and other factors seen in several advanced cancers. Independent of anorexia, although frequently associated (where it is referred to as the cachexia-anorexia syndrome), it accounts for a significant amount of morbidity and deaths in people with cancer. In particular, quality of life for the patient and the family is significantly affected with this syndrome as it causes anxiety and distress. Therefore, it is important that research into therapies is undertaken, particularly focusing on an understanding of the pharmacokinetic properties of compounds in this cachexic population. Cannabinoids are one such group of therapies that have received a large amount of media focus recently. However, there appears to be a lack on rigorous pharmacokinetic data of these complex and varied compounds in the cachexic population. Similarly, there is a lack of pharmacokinetic data in any population group for the non- tetrahydrocannabinol (THC) and cannabidiol (CBD) cannabinoids (often due to the lack of analytical standards for quantification). This review will thus examine the pharmacokinetics of major cannabinoids i.e. THC and CBD in a cancer population. Overall, based on the current literature, evidence for the use of cannabinoids for the treatment of cancer-related cachexia-anorexia syndrome remains equivocal. A high-quality, rigorous, phase I/II study to elicit pharmacokinetic dose¿concentration and concentration¿response data, with a clinically acceptable mode of delivery to reduce intrapatient variability and enable more consistent bioavailability is needed in this population.
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2015 |
O'Hara K, Wright IMR, Schneider JJ, Jones AL, Martin JH, 'Pharmacokinetics in neonatal prescribing: Evidence base, paradigms and the future', British Journal of Clinical Pharmacology, 80 1281-1288 (2015) [C1] Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing inform... [more] Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients.
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2015 |
Martin JH, Ferro A, 'From an evolutionary perspective, all 'new' antimicrobial targets are old: Time to think outside the box', British Journal of Clinical Pharmacology, 79 165-167 (2015) [C3]
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2015 |
Lim AE, Tate JR, Clarke D, Norris RL, Morris RG, Martin JH, 'Clinical Consequences of a Miscalibrated Digoxin Immunoassay', THERAPEUTIC DRUG MONITORING, 37 104-109 (2015) [C1]
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2015 |
Diaz A, Moore SP, Martin JH, Green AC, Garvey G, Valery PC, 'Factors associated with cancer-specific and overall survival among indigenous and non-indigenous gynecologic cancer patients in Queensland, Australia: A matched cohort study', International Journal of Gynecological Cancer, 25 542-547 (2015) [C1] Objective: Aboriginal and Torres Strait Islander women have a higher mortality rate due to gynecologic cancer compared with non-Indigenous women. For cervical cancer, Australian I... [more] Objective: Aboriginal and Torres Strait Islander women have a higher mortality rate due to gynecologic cancer compared with non-Indigenous women. For cervical cancer, Australian Indigenous women are less likely to survive 5 years following diagnoses than non-Indigenous women. This study investigates the factors associated with gynecologic cancer treatment and survival among Queensland indigenous and non-Indigenous women. Methods: Australian Indigenous women diagnosed with uterine, cervical, ovarian, or other gynecologic cancers during 1998-2004 in the public hospital system were included. They were frequency matched on age (±5 years), residential remoteness, and cancer type to a random sample of non-Indigenous women. One- and 5-year cancer-specific survival was examined according to Indigenous status using Cox proportional hazards regression. Results: Indigenous women (n = 137) compared with non-Indigenous women (n = 120) were less likely to be diagnosed with localized disease (49% vs 65%, P = 0.02) and had more comorbidities (52% vs 21%, P < 0.001). Indigenous women were less likely to receive any cancer treatment compared with non-Indigenous women (91% vs 98%, P = 0.01), although when excluding those with metastatic cancer, there was no significant difference in uptake of treatment (95% vs 91%, respectively, P = 0.31). Among those who did undergo treatment, there was no difference in time to treatment (median difference 0.5 days, P = 0.98). Gynecologic cancer-specific survival differences between Indigenous and non-Indigenous women were most prominent in the first year following diagnosis (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.06-3.38) and were no longer significant 5 years after diagnosis (HR, 1.47 [95% CI, 0.97-2.25]). For cervical cancer, crude 1-year survival was poorer for Indigenous women compared with non-Indigenous women (HR, 2.46 [95% CI, 1.03-5.90]), but was no different when adjusted for stage and treatment of cancer (HR, 1.00 [95% CI, 0.45-2.24]). Conclusions: Improving the early diagnosis of cervical cancer in Indigenous women may increase cancer-specific survival in the year following diagnosis.
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2015 |
Lindsay J, Dooley M, Martin J, Fay M, Kearney A, Khatun M, Barras M, 'The development and evaluation of an oncological palliative care deprescribing guideline: the 'OncPal deprescribing guideline'', SUPPORTIVE CARE IN CANCER, 23 71-78 (2015) [C1]
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2015 |
Liu X, Vitetta L, Kostner K, Crompton D, Williams G, Brown WJ, et al., 'The effects of tai chi in centrally obese adults with depression symptoms', Evidence-based Complementary and Alternative Medicine, 2015 (2015) [C1] This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevate... [more] This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevated depression symptoms. In total, 213 participants were randomized to a 24-week Tai Chi intervention program or a wait-list control group. Assessments were conducted at baseline and 12 and 24 weeks. Outcomes were severity of depression, anxiety, and stress symptoms, leg strength, central obesity, and other measures of metabolic symptom. There were statistically significant between-group differences in favor of the Tai Chi group in depression (mean difference = -5.6 units, P < 0.001), anxiety (-2.3 units, P < 0.01), and stress (-3.6 units, P < 0.001) symptom scores and leg strength (1.1 units, P < 0.001) at 12 weeks. These changes were further improved or maintained in the Tai Chi group relative to the control group during the second 12 weeks of follow-up. Tai Chi appears to be beneficial for reducing severity of depression, anxiety, and stress and leg strength in centrally obese people with depression symptoms. More studies with longer follow-up are needed to confirm the findings. This trial is registered with ACTRN12613000010796.
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2015 |
Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al., 'Global surveillance of cancer survival 1995-2009: Analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)', The Lancet, 385 977-1010 (2015) Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as ... [more] Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. Interpretation International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. Funding Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).
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2015 |
Fay M, Head R, Martin J, 'Where is the radiobiology and pharmacology research to improve outcomes in glioblastoma?', Journal of Neuro-Oncology, (2015) [C1] Personalized medicine has been helpful for drug development in diseases with single and relatively stable gene mutations. The benefit for complex solid tumours with heterogeneous ... [more] Personalized medicine has been helpful for drug development in diseases with single and relatively stable gene mutations. The benefit for complex solid tumours with heterogeneous and changing genetic profiles is less clear. Whether it is efficient to continue diverting resources from combined biological and pharmacological approaches to trial new and existing genetic ¿targeted therapies¿ for brain tumours is unknown but of developing concern in resource constrained environments.
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2015 |
Valery PC, Powell E, Moses N, Volk ML, McPhail SM, Clark PJ, Martin J, 'Systematic review: unmet supportive care needs in people diagnosed with chronic liver disease', BMJ OPEN, 5 (2015) [C1]
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2015 |
Rundle-Thiele D, Day B, Stringer B, Fay M, Martin J, Jeffree RL, et al., 'Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: Importance of analytical method', Journal of Medical Radiation Sciences, 62 92-98 (2015) [C1] Introduction: Accurate knowledge of O6-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this t... [more] Introduction: Accurate knowledge of O6-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. Methods: We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. Results: A strong trend between a measure of 'minimum ADC' and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the 'low ADC' component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). Conclusion: This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.
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2015 |
Scott IA, Hilmer SN, Reeve E, Potter K, Couteur DL, Rigby D, et al., 'Reducing inappropriate polypharmacy: The process of deprescribing', JAMA Internal Medicine, 175 827-834 (2015) [C1] Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single mo... [more] Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.
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2015 |
Hosein AN, Lim YC, Day B, Stringer B, Rose S, Head R, et al., 'The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells', Journal of Neuro-Oncology, 122 263-271 (2015) [C1] Glioblastoma multiforme (GBM) has nearly uniformly fatal with a median survival of less than 2¿years. While there have not been any novel anti-GBM therapeutics approved for many y... [more] Glioblastoma multiforme (GBM) has nearly uniformly fatal with a median survival of less than 2¿years. While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients. This pre-clinical study aimed to determine the potential clinical utility of VPA in the treatment of GBM. Primary GBM cells were treated with VPA as a monotherapy and in combination with temozolomide and irradiation. At clinically achievable concentrations, VPA was shown to be effective as a monotherapy agent in the five primary lines tested. VPA was then used as a sensitizing agent to in vitro radiation and showed significant augmentation of in vitro irradiation therapy. In addition, when VPA, radiation and temozolomide were combined an additive, rather than synergistic effect was noted. Gene expression profiling demonstrated close clustering of triple treated cells with VPA mono-treated cells while untreated cells clustered closer with TMZ-irradiation dual treated cells. These microarray data suggest a dominant role of VPA at the gene expression level when combining these different treatment options. Moreover, in an in vivo tumor transplantation model, we were able to demonstrate an increase in animal survival when cells were pre-treated with irradiation-VPA and when triple treated. These findings provide a significant rationale for the investigation of VPA in the treatment of GBM patients.
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2015 |
Hubbard RE, Peel NM, Scott IA, Martin JH, Smith A, Pillans PI, et al., 'Polypharmacy among inpatients aged 70 years or older in Australia', MEDICAL JOURNAL OF AUSTRALIA, 202 373-+ (2015) [C1]
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2015 |
Martin JH, Phillips E, Thomas D, Somogyi AA, 'Adding the 'medicines' back into personalized medicine to improve cancer treatment outcomes', British Journal of Clinical Pharmacology, 80 929-931 (2015) [C3]
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2014 |
Williams MM, Taylor PJ, Page CB, Martin JH, 'Clinical research in synthetic cannabinoids - do we need a national approach?', Med J Aust, 201 317-319 (2014) [C3]
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2014 |
Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, et al., 'Resveratrol Does Not Benefit Patients With Nonalcoholic Fatty Liver Disease', Clinical Gastroenterology and Hepatology, 12 2092-2103.e6 (2014) [C1] Background & Aims: Nonalcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin ... [more] Background & Aims: Nonalcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism. We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD. Methods: Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane, Australia from 2011 through 2012. They were randomly assigned to groups given 3000 mg resveratrol (n= 10) or placebo (n= 10) daily for 8 weeks. Outcomes included insulin resistance (assessed by the euglycemic-hyperinsulinemic clamp), hepatic steatosis, and abdominal fat distribution (assessed by magnetic resonance spectroscopy and imaging). Plasma markers of inflammation, as well as metabolic, hepatic, and antioxidant function, were measured; transcription of target genes was measured in peripheral blood mononuclear cells. Resveratrol pharmacokinetics and safety were assessed. Results: Eight-week administration of resveratrol did not reduce insulin resistance, steatosis, or abdominal fat distribution when compared with baseline. No change was observed in plasma lipids or antioxidant activity. Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group. Resveratrol did not significantly alter transcription of NQO1, PTP1B, IL6, or HO1 in peripheral blood mononuclear cells. Resveratrol was well-tolerated. Conclusions: Eight weeks administration of resveratrol did not significantly improve any features of NAFLD, compared with placebo, but it increased hepatic stress, based on observed increases in levels of liver enzymes. Further studies are needed to determine whether agents that are purported to mimic calorie restriction, such as resveratrol, are safe and effective for complications of obesity. Clinical trials registration no: ACTRN12612001135808.
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2014 |
Hollingworth SA, Ostini R, Michael D, Martin J, Susan T, 'Use of Ezetimibe in Australia', PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, 23 130-131 (2014)
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2014 |
Theile DE, Scott IA, Martin JH, Gavrilidis A, 'Enabling the success of academic health science centres in Australia: where is the leadership?', The Medical journal of Australia, 201 636-638 (2014) [C3]
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2014 |
Leung J, McKenzie S, Martin J, McLaughlin D, 'Effect of rurality on screening for breast cancer: a systematic review and meta-analysis comparing mammography', Rural and remote health, 14 2730 (2014) INTRODUCTION: The lower breast cancer survival rate observed among rural women may be related to differences in screening access and utilization. We evaluated existing evidence fo... [more] INTRODUCTION: The lower breast cancer survival rate observed among rural women may be related to differences in screening access and utilization. We evaluated existing evidence for rural and urban differences in mammography service use in adult women.
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2014 |
Fay MF, Martin JH, Rose S, 'New imaging techniques for more effective treatment in glioblastoma', Internal Medicine Journal, 44 5-6 (2014) [C3]
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2014 |
Martin JH, Coombes I, 'Mortality from common drug interactions systems, knowledge and clinical reasoning to optimise prescribing', Internal Medicine Journal, 44 621-624 (2014) [C3]
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2013 |
Forbes MP, Raj AS, Martin J, Lampe G, Powell EE, 'Khat-associated hepatitis', Medical Journal of Australia, 199 498-499 (2013)
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2013 |
Putt MT, Udy AA, Jarrett P, Martin J, Hennig S, Salmon N, et al., 'Phenytoin loading doses in adult critical care patients: Does current practice achieve adequate drug levels?', Anaesthesia and Intensive Care, 41 602-609 (2013) Phenytoin is regularly employed in the critically ill for prophylaxis against or treatment of seizure disorders. No prior studies have examined current dosing practices in an Aust... [more] Phenytoin is regularly employed in the critically ill for prophylaxis against or treatment of seizure disorders. No prior studies have examined current dosing practices in an Australasian intensive care unit (ICU) setting. The aims of this study were to: a) describe the adequacy of contemporary dosing in respect to free and total serum phenytoin concentrations; b) identify factors associated with therapeutic drug concentrations; and c) examine the accuracy of predictive equations that estimate free concentrations in this setting. All patients receiving a loading dose of phenytoin in a tertiary-level ICU were eligible for enrolment; 53 patients were enrolled in the study. Serum samples to determine free and total phenytoin concentrations (measured by high performance liquid chromatography) were then drawn prior to the following dose. Free concentrations below the recommended target (<1 mg/l) were considered as suboptimal. The most common indication for phenytoin loading was traumatic brain injury (49%) and the mean administered dose was 14.5 (3.66) mg/kg. Twenty-six patients (49%) had suboptimal trough free concentrations, although this subgroup was significantly heavier and therefore received a lower per kilogram dose (12.8 [3.1] vs 16.3 [3.4] mg/kg, P=0.001). In multivariate analysis, larger weight adjusted doses (P=0.018), higher albumin concentration (P=0.034) and receiving phenytoin for an indication other than seizure (P=0.035), were associated with a greater likelihood of adequate concentrations. In conclusion, phenytoin dosing remains complex in critically ill patients, although lower per kilogram loading doses are strongly associated with free concentrations below the desired target.
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2013 |
Lucas C, Martin J, 'Smoking and drug interactions', Australian Prescriber, 36 102-104 (2013) When patients enter hospital they may have to stop smoking abruptly if the hospital has a 'no smoking' policy. Abrupt smoking cessation can affect the metabolism of drug... [more] When patients enter hospital they may have to stop smoking abruptly if the hospital has a 'no smoking' policy. Abrupt smoking cessation can affect the metabolism of drugs. Cigarette smoking induces the activity of human cytochromes P450 (CYP) 1A2 and 2B6. These enzymes metabolise several clinically important drugs, including clozapine, olanzapine and methadone. Decreased CYP1A2 activity after smoking cessation increases the risk of adverse drug reactions, with reports of increased toxicity from clozapine and olanzapine. Predicting the required dose reduction of drugs metabolised by CYP1A2 after smoking cessation is challenging. Therapeutic drug monitoring should be used when possible. Nicotine replacement therapy does not influence CYP1A2 activity.
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2013 |
Thomas C, Martin J, Devic C, Bräuer-Krisch E, Diserbo M, Thariat J, Foray N, 'Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response', International Journal of Radiation Biology, 89 813-822 (2013) [C1] Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) ce... [more] Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) cells. Methods: Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with 60Co ¿-rays at 0.0025-500 mGy.min-1. Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min-1 with 75 kV X-rays only. Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (tHRSmax and tIRRmax) were independent of dose-rate. The tHRSmax and tIRRmax values were 23 ± 5 s and 66 ± 7 s (mean ± standard error of the mean [SEM], n = 7), in agreement with literature data. Repair data show that tHRSmax may correspond to exposure time during which NHEJ is deficient while tIRRmax may correspond to exposure time during which NHEJ is complete. Conclusion: HRS response may be maximal if exposure times are shorter than tHRSmax irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed. © 2013 Informa UK, Ltd.
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2013 |
Hubbard RE, Peel NM, Scott IA, Martin JH, Pillans P, Gray LC, 'Polypharmacy among older inpatients in Australia', AUSTRALASIAN JOURNAL ON AGEING, 32 24-24 (2013)
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Show 327 more journal articles |
Conference (101 outputs)
Year | Citation | Altmetrics | Link | |||||
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2023 |
Martin JH, Head R, 'Drug Repurposing in Chemoresistance', Drug Repurposing in Chemoresistance
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2022 |
Dimmitt SB, Kennedy MC, Stampfer HG, Martin JH, 'MARGINAL BENEFITS OF STATINS IN ASYMPTOMATIC PATIENTS - FIRST DO NO HARM', INTERNAL MEDICINE JOURNAL (2022)
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2022 |
Glewis S, Lingaratnam S, Krishnasamy M, Martin J, Tie J, Alexander M, Michael M, 'Pharmacogenetic testing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1) based chemotherapies in routine clinical care: Perspectives of medical oncologists and oncology pharmacists', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2022)
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2020 |
Weller SR, Martin JH, 'On strongly unimodal third-order SISO linear systems with applications to pharmacokinetics', 1st Virtual IFAC World Congress (IFAC-V 2020), Online (2020) [E1]
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2015 |
Aithal GP, Nicoletti P, Bjornsson E, Lucena MI, Andrade RJ, Grove J, et al., 'HLA-A*33:01 is strongly associated with drug-induced liver injury (DILI) due to terbinafine and several other unrelated compounds', HEPATOLOGY (2015) [E3]
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2015 |
Diaz A, Moore SP, Martin JH, Green AC, Garvey G, Valery PC, 'Comorbidities amongst Indigenous Cancer Patients: Impact on Treatment and Survival.', INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Anchorage, AK (2015)
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2015 |
Diaz A, Moore SP, Martin JH, Green AC, Coory M, Garvey G, Valery PC, 'Early Diagnosis and Improved Treatment Uptake in the First Year may Reduce Survival Disparities between Aboriginal and Torres Strait Islander and other Australian Women Diagnosed with Gynaecological Cancer', INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Anchorage, AK (2015)
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2015 |
Fay M, Sakoff J, Martin J, Rose S, Crozier S, Boyd A, et al., 'EPHA2 ANTIBODY INCREASES SENSITIVITY OF U87 GLIOBLASTOMA CELLS TO IRRADIATION', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
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2015 |
Goulooze S, Martin J, 'MONTE-CARLO SIMULATIONS OF THE CLINICAL BENEFITS FROM THERAPEUTIC DRUG MONITORING OF SUNITINIB IN PATIENTS WITH GASTROINTESTINAL STROMAL TUMOURS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
|
|||||||
2015 |
Garg M, Galettis P, Goulooze S, Clingan P, Ranson M, Sakoff J, et al., 'THERAPEUTIC DRUG MONITORING FOR CANCER PATIENTS RECEIVING CHEMOTHERAPY', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
|
|||||||
2014 |
Tam L, Meiklejohn J, Garvey G, Martin J, Adams J, Walpole E, et al., 'SUPPORTING ABORIGINAL AND TORRES STRAIT ISLANDER PEOPLE DIAGNOSED WITH CANCER TO NAVIGATE THE HEALTHCARE SYSTEM', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
|
|||||||
2014 |
Linda N, Cheng M, Protani M, Martin J, Fay M, 'RELATIONSHIP BETWEEN OBESE WOMEN WITH BREAST CANCER, THEIR SOCIOECONOMIC STATUS AND COMORBIDITIES', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
|
|||||||
2014 |
Cheng M, Linda N, Protani M, Carroll J, Fay M, Martin J, 'OBESITY A RISK FACTOR FOR CHEMOTHERAPY DOSE REDUCTION IN BREAST CANCER: A MULTI-CENTERED APPROACH', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
|
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Show 98 more conferences |
Preprint (1 outputs)
Year | Citation | Altmetrics | Link | |||||
---|---|---|---|---|---|---|---|---|
2023 |
Matthews B, Wong-Brown M, Liu D, Yee C, Dickson K-A, Schneider J, et al., 'Drug repurposing screen targeting PARP identifies cytotoxic activity of efavirenz in high-grade serous ovarian cancer (2023)
|
Grants and Funding
Summary
Number of grants | 66 |
---|---|
Total funding | $22,704,051 |
Click on a grant title below to expand the full details for that specific grant.
20232 grants / $43,620
Cannabidiol may protect the brain against the harmful effects of marijuana $30,500
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Doctor Peter Galettis, Professor Jennifer Martin, Professor Murat Yucel, Professor Nadia Solowij |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2201296 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
An open label pilot study investigating the in vivo detection of tetrahydrocannabinol (THC) in cannabidiol (CBD) dominant cannabinoid medications$13,120
Funding body: Mater Research Limited
Funding body | Mater Research Limited |
---|---|
Project Team | Doctor Peter Galettis, Professor Phillip Good, Doctor Taylan Gurgenci, Professor Janet Hardy, Professor Jennifer Martin, Doctor Russell Richard |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2300007 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20211 grants / $36,750
An open label study to evaluate the safety, tolerability, and pharmacokinetics of a medicinal cannabinoid oil formulation in chronic non-cancer pain patients$36,750
Funding body: St Vincents Hospital (Melbourne) Limited
Funding body | St Vincents Hospital (Melbourne) Limited |
---|---|
Project Team | Doctor Peter Galettis, Professor Jennifer Martin |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2021 |
Funding Finish | 2021 |
GNo | G2100769 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20206 grants / $3,136,929
Australian Program for Drug Repurposing for Ovarian Cancer Treatment$2,736,499
Funding body: Department of Health and Aged Care
Funding body | Department of Health and Aged Care |
---|---|
Project Team | Professor Nikola Bowden, Professor Jennifer Martin, Doctor Michelle Brown, Associate Professor Deborah Marsh, Associate Professor Deborah Marsh, Caroline Ford, Dr David Thomas, Dr David Thomas, Emeritus Professor Richard Head, Ms Penny Reeves, Ms Gill Stannard |
Scheme | MRFF - EPCDR - Ovarian Cancer |
Role | Investigator |
Funding Start | 2020 |
Funding Finish | 2025 |
GNo | G2000012 |
Type Of Funding | C1300 - Aust Competitive - Medical Research Future Fund |
Category | 1300 |
UON | Y |
Growing the medicinal cannabis industry – precision farming to pharmaceuticals$145,600
Funding body: Department of Industry, Innovation and Science
Funding body | Department of Industry, Innovation and Science |
---|---|
Project Team | Professor Jennifer Martin, Doctor Peter Galettis |
Scheme | Cooperative Research Centres (CRC) Projects |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G1901122 |
Type Of Funding | CRC - Cooperative Research Centre |
Category | 4CRC |
UON | Y |
NSW Cannabis Medicines Advisory Service research projects$128,021
Funding body: Hunter New England Local Health District
Funding body | Hunter New England Local Health District |
---|---|
Project Team | Ms Myfanwy Graham, Professor Jennifer Martin, Associate Professor Jenny Schneider, Doctor Catherine Lucas |
Scheme | Research Funding |
Role | Investigator |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G2001016 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
A phase I/II double-blind, randomised controlled trial assessing effect of medicinal cannabis on quality of life and symptom control in advanced cancer” (RESONANCE) Study$52,800
Funding body: Olivia Newton-John Cancer Research Institute
Funding body | Olivia Newton-John Cancer Research Institute |
---|---|
Project Team | Professor Jennifer Martin, Doctor Peter Galettis, Dr Aron Wong |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G2000938 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
The feasibility and acceptability of using fingerprick blood sampling to monitor blood immunosuppressant concentrations in renal transplant recipients.$45,455
Funding body: Kidney Health Australia
Funding body | Kidney Health Australia |
---|---|
Project Team | Associate Professor Jenny Schneider, Doctor Peter Galettis, Professor Jennifer Martin, Doctor Paul Trevillian, Dr Frank Reimann |
Scheme | Medical and Scientific Research Grant |
Role | Investigator |
Funding Start | 2020 |
Funding Finish | 2021 |
GNo | G2000174 |
Type Of Funding | C1700 - Aust Competitive - Other |
Category | 1700 |
UON | Y |
Research Funding for Treatment of alcohol dependence with an mTOR inhibitor (TAMI) Study$28,554
Funding body: Hunter New England Local Health District
Funding body | Hunter New England Local Health District |
---|---|
Project Team | Conjoint Professor Adrian Dunlop, Doctor Amanda Brown, Professor Chris Dayas, Dr MADELEINE Hinwood, Professor Jennifer Martin |
Scheme | Research Funding |
Role | Investigator |
Funding Start | 2020 |
Funding Finish | 2023 |
GNo | G2000584 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
20194 grants / $293,806
Early phase high throughput studies of cannabinoids using new understandings of glioblastoma biology, radiobiology and pharmacology$190,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Jennifer Martin, Doctor Michael Fay, Doctor James Lynam, Doctor Catherine Lucas, Doctor Peter Galettis, Professor Nikola Bowden, Associate Professor Jenny Schneider, Associate Professor Paul Tooney, Doctor Ross Norris, Doctor Moira Graves |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2019 |
Funding Finish | 2021 |
GNo | G1900511 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
Repurposing existing drugs to overcome ovarian cancer chemoresistance$67,806
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Nikola Bowden, Doctor Michelle Brown, Professor Jennifer Martin, Emeritus Professor Richard Head |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2019 |
Funding Finish | 2019 |
GNo | G1901179 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
Repurposing drugs into effective cancer treatments$25,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Jennifer Martin, Professor Nikola Bowden, Emeritus Professor Richard Head |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2019 |
Funding Finish | 2020 |
GNo | G1901341 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
Feasibility of monitoring immunosuppressant drugs using dried blood spot technology$11,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Jenny Schneider, Doctor Peter Galettis, Professor Jennifer Martin, Dr Frank Reimann |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2019 |
Funding Finish | 2020 |
GNo | G1901318 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20184 grants / $6,450,707
The NSW Clinical Cannabis Medicines Program$4,443,754
Funding body: NSW Ministry of Health
Funding body | NSW Ministry of Health |
---|---|
Project Team | Professor Jennifer Martin, Associate Professor Jenny Schneider, Doctor Peter Galettis, Doctor Catherine Lucas |
Scheme | Research Funds |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2020 |
GNo | G1701636 |
Type Of Funding | C2300 – Aust StateTerritoryLocal – Own Purpose |
Category | 2300 |
UON | Y |
PREDICT — Pathway of Research to Evaluation of Dose-Individualised Cancer Therapy: Development of a national individualised cancer dosing program to both generate evidence and implement existing evi$1,961,953
Funding body: Cancer Council NSW
Funding body | Cancer Council NSW |
---|---|
Project Team | Professor Jennifer Martin, Conjoint Professor Stephen Ackland, Professor Howard Gurney, Professor Paul de Souza, Dr Stephanie Reuter Lange, Doctor Peter Galettis, Professor Alan Boddy, Professor Michael Michael, Professor Paul Scuffham |
Scheme | Pathways to a Cancer-Free Future |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2022 |
GNo | G1701238 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
HMRI Award for Research Excellence$25,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Research Excellence Award |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | G1900121 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
A simple fingerprick and blood test to optimize chemotherapy dosing in oesophageal cancer$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Jenny Schneider, Doctor Peter Galettis, Professor Jennifer Martin, Conjoint Professor Stephen Ackland, Doctor Catherine Lucas |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | G1800190 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20178 grants / $3,066,892
Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE): Quality and safety in the implementation of medicinal cannabis use in the community$2,596,199
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Jennifer Martin, Professor Nadia Solowij, Professor Jane Gunn, Associate Professor Nicholas Lintzeris, Professor Xu-Feng Huang, Professor Kathy Eagar, Kathy Eager, Professor Nanthi Bolan, Professor Paul Scuffham, Associate Professor Yvonne Bonomo, Doctor Amirali Popat, Professor Nanthi Bolan |
Scheme | Centres of Research Excellence - Centres of Clinical Research Excellence (CRE) |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2022 |
GNo | G1601347 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
Feasibility of minimally invasive, reliable and reproducible blood sampling techniques for chemotherapy dose optimisation in breast cancer$200,000
Funding body: National Breast Cancer Foundation
Funding body | National Breast Cancer Foundation |
---|---|
Project Team | Professor Jennifer Martin, Associate Professor Jenny Schneider, Conjoint Professor Stephen Ackland |
Scheme | Pilot Study Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2018 |
GNo | G1600810 |
Type Of Funding | Aust Competitive - Non Commonwealth |
Category | 1NS |
UON | Y |
SDVCRI Research Support for NHMRC CRE$169,715
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Internal Research Support |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2022 |
GNo | G1800751 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
NSW PhD Scholarships Program 2017 - Berling$40,000
Funding body: NSW Ministry of Health
Funding body | NSW Ministry of Health |
---|---|
Project Team | Professor Jennifer Martin, Conjoint Professor Ian Whyte, Dr Ingrid Berling |
Scheme | PhD Scholarships Program |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2018 |
GNo | G1700886 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
Defining and predicting clinical toxicity in GBM patients undergoing temozolomide-radiation treatment: A multivariate study$25,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Doctor James Lynam, Doctor Jennette Sakoff, Professor Jennifer Martin, Doctor Lisa Lincz, Doctor Michael Fay, Doctor Peter Galettis |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700586 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
Use of prochlorperazine to enable efficacy of targeted therapies in head and neck cancer$23,252
Funding body: Calvary Mater Newcastle
Funding body | Calvary Mater Newcastle |
---|---|
Project Team | Professor Jennifer Martin, Conjoint Professor Stephen Ackland |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700472 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
Australian Centre for Cannabinoid Clinical and Research Excellence Education and Policy.$9,999
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Linkage Pilot Research Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2018 |
GNo | G1701190 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
Analysis of qualitative data from interviews with Indigenous cancer patients$2,727
Funding body: QIMR Berghofer Medical Research Institute
Funding body | QIMR Berghofer Medical Research Institute |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Small Research Consultancy |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700817 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20167 grants / $107,936
Analysis of Cannabinoids$25,000
Funding body: University of Wollongong
Funding body | University of Wollongong |
---|---|
Project Team | Professor Jennifer Martin, Doctor Peter Galettis |
Scheme | Research Consultancy |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | G1601398 |
Type Of Funding | Scheme excluded from IGS |
Category | EXCL |
UON | Y |
Research Consultancy – Australian Cancer Research Fund consumable for PK$23,300
Funding body: University of Queensland
Funding body | University of Queensland |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Small Research Consultancy |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | G1600683 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
Profiling Human Cardiac Stem Cells$21,745
Funding body: John Hunter Hospital Charitable Trust
Funding body | John Hunter Hospital Charitable Trust |
---|---|
Project Team | Professor Andrew Boyle, Professor Jennifer Martin |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | G1600704 |
Type Of Funding | Other Public Sector - State |
Category | 2OPS |
UON | Y |
Use of prochlorperazine to enable efficacy of targeted therapies in head and neck cancer (Equipment component).$13,252
Funding body: Calvary Mater Newcastle
Funding body | Calvary Mater Newcastle |
---|---|
Project Team | Jennifer Martin and Stephen Ackland |
Scheme | Coalfields Equipment Fund |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Other Public Sector - Local |
Category | 2OPL |
UON | N |
Use of prochlorperazine to enable efficacy of targeted therapies in head and neck cancer (Equipment component)$10,000
Funding body: Calvary Mater Newcastle
Funding body | Calvary Mater Newcastle |
---|---|
Project Team | Jennifer Martin and Stephen Ackland |
Scheme | HCRA Clinical Cancer Fund |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Other Public Sector - Local |
Category | 2OPL |
UON | N |
Use of prochlorperazine to enable efficacy of targeted therapies in head and neck cancer.$7,706
Funding body: Calvary Mater Newcastle 2016-2017 round of Research Grants
Funding body | Calvary Mater Newcastle 2016-2017 round of Research Grants |
---|---|
Project Team | Jennifer Martin and Stephen Ackland |
Scheme | James Lawrie Grant Scheme |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Other Public Sector - Local |
Category | 2OPL |
UON | N |
Effect of body size on chemotheraphy dose and blood concentrations in cancer$6,933
Funding body: Metro South Health
Funding body | Metro South Health |
---|---|
Project Team | Professor Jennifer Martin |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | G1601272 |
Type Of Funding | Other Public Sector - State |
Category | 2OPS |
UON | Y |
20151 grants / $500,000
High resolution fourier transform mass spectrometry platform for the discovery of novel cancer biomarkers and drug targets using label-free and isobaric-tagged approaches for quantitative proteomics.$500,000
Funding body: Cancer Institute NSW
Funding body | Cancer Institute NSW |
---|---|
Project Team | Professor Xu Dong Zhang, Professor Matt Dun, Professor Jennifer Martin, Professor Hubert Hondermarck, Distinguished Emeritus Professor John Aitken, Associate Professor Nikki Verrills, Professor Pradeep Tanwar, Professor Rodney Scott, Professor Maria Kavallaris, Dr Darren Saunders |
Scheme | Research Equipment Grant |
Role | Investigator |
Funding Start | 2015 |
Funding Finish | 2016 |
GNo | G1500599 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
20142 grants / $266,651
Targeting existing therapies with innovative technology platforms to improve survival in brain cancer$200,000
Funding body: Cancer Council Queensland
Funding body | Cancer Council Queensland |
---|---|
Scheme | Project grant |
Role | Investigator |
Funding Start | 2014 |
Funding Finish | 2014 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Effect of obesity on exposure to breast cancer chemotherapy: still a need to 'cap' the dose?$66,651
Funding body: University of Queensland
Funding body | University of Queensland |
---|---|
Project Team | Professor Jennifer Martin, Doctor Peter Galettis |
Scheme | Research Project |
Role | Lead |
Funding Start | 2014 |
Funding Finish | 2016 |
GNo | G1601146 |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | Y |
20134 grants / $685,596
Improving systems and quality of cancer care in Aboriginal and Torres Strait Islander primary health care settings$640,096
Funding body: National Health & Medical Research Council
Funding body | National Health & Medical Research Council |
---|---|
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
University of Queensland Post Doctoral Scholarship for Women$37,500
Funding body: The University of Queensland
Funding body | The University of Queensland |
---|---|
Scheme | Scholarship |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
The clinical pharmacology of valproate$6,000
Funding body: Deutsche Akademische Austauschdienst
Funding body | Deutsche Akademische Austauschdienst |
---|---|
Scheme | Discovery project |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Clinical assessment of a predictive pharmacokinetic program for individualised vancomycin dosing in paediatrics$2,000
Funding body: Mater Hospitals, Brisbane
Funding body | Mater Hospitals, Brisbane |
---|---|
Scheme | Discovery project |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2013 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20129 grants / $3,146,502
The diamantina individualised oncology care centre$2,000,000
Funding body: Australian Cancer Research Foundation
Funding body | Australian Cancer Research Foundation |
---|---|
Project Team | M. Brown |
Scheme | Cancer Research Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Improving systems and quality of cancer care in Aboriginal and Torres Strait Islander primary health care settings$617,502
Funding body: National Health & Medical Research Council
Funding body | National Health & Medical Research Council |
---|---|
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | N |
Effect of body size on chemotherapy dose and blood concentrations in cancer$150,000
Funding body: Princess Alexandra Hospital and District Health Service, QLD
Funding body | Princess Alexandra Hospital and District Health Service, QLD |
---|---|
Scheme | Early Career Fellowship |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
The effect of valproate on surrogate markers of prognosis in glioblastoma multiforme$105,000
Funding body: Royal Brisbane Hospital
Funding body | Royal Brisbane Hospital |
---|---|
Project Team | M. Fay; I. Jeffree; A. Boyd; S. Rose; S. Robertson |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Indigenous community 'champion' project$79,000
Funding body: Cure Cancer Australia Foundation
Funding body | Cure Cancer Australia Foundation |
---|---|
Project Team | Valery, P; Garvey, G; Walpole, E. |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Establishment of primary human liver cell isolation: a necessary model to understand hepatic disease$75,000
Funding body: Princess Alexandra Hospital and District Health Service, QLD
Funding body | Princess Alexandra Hospital and District Health Service, QLD |
---|---|
Project Team | Elizabeth Powell |
Scheme | Foundation grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Effect of obesity on concentrations of breast cancer drugs and survival$75,000
Funding body: Princess Alexandra Hospital and District Health Service, QLD
Funding body | Princess Alexandra Hospital and District Health Service, QLD |
---|---|
Scheme | Foundation grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Are modern methods for aminoglycoside monitoring superior to existing approaches? a randomised controlled trial$35,000
Funding body: Royal Brisbane Hospital
Funding body | Royal Brisbane Hospital |
---|---|
Project Team | M. Barris, I. Coombes, J. Roberts, D. Paterson |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Optimising pain management with fentanyl in patients with cancer$10,000
Funding body: Griffith Health Institute
Funding body | Griffith Health Institute |
---|---|
Scheme | MBOD Project Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20112 grants / $766,814
A comparative study: patterns of care, comorbidities and quality of life of Indigenous and non-Indigenous people with lung, head & neck, breast or gynaecological cancers$691,814
Funding body: National Health & Medical Research Council
Funding body | National Health & Medical Research Council |
---|---|
Scheme | Discovery project |
Role | Investigator |
Funding Start | 2011 |
Funding Finish | 2013 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
A new prescribing technology for older patients$75,000
Funding body: Princess Alexandra Hospital and District Health Service, QLD
Funding body | Princess Alexandra Hospital and District Health Service, QLD |
---|---|
Project Team | Ian Scott, Len Gray |
Scheme | Foundation grant |
Role | Investigator |
Funding Start | 2011 |
Funding Finish | 2011 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20102 grants / $1,779,000
Health workforce Australia capital agreement$1,100,000
Funding body: Redlands / QEII Hospital
Funding body | Redlands / QEII Hospital |
---|---|
Scheme | Discovery project |
Role | Lead |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Patterns of care, comorbidities and quality of life in Indigenous people with cancer$679,000
Funding body: National Health & Medical Research Council
Funding body | National Health & Medical Research Council |
---|---|
Scheme | Project Grant |
Role | Lead |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20092 grants / $74,848
Non-invasive cardiac imaging in the detection and assessment of subclinical diabetic heart disease$54,848
Funding body: National Heart Foundation of Australia
Funding body | National Heart Foundation of Australia |
---|---|
Project Team | C. Jellis |
Scheme | NSW Cardiovascular Research Network (CVRN) Research Development Project Grant |
Role | Investigator |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Relationship between obesity, chemotherapy dose and outcome in women with node positive breast cancer $20,000
Funding body: RBWH Clinical School, Faculty of Health Sciences, University of Queensland (Australia)
Funding body | RBWH Clinical School, Faculty of Health Sciences, University of Queensland (Australia) |
---|---|
Scheme | Discovery project |
Role | Lead |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20082 grants / $40,000
The risk of cardiovascular disease post allogeneic bone marrow transplant: role of the peripheral blood mononuclear cell$30,000
Funding body: Clive & Vera Ramaciotti
Funding body | Clive & Vera Ramaciotti |
---|---|
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2008 |
Funding Finish | 2008 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Free phenytoin in severley unwell hospitalised populations$10,000
Funding body: Pathology Queensland
Funding body | Pathology Queensland |
---|---|
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2008 |
Funding Finish | 2008 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20071 grants / $40,000
Melbourne University Inter-faculty and Cross-disciplinary Steering Comittee Grant$40,000
Funding body: The University of Melbourne
Funding body | The University of Melbourne |
---|---|
Project Team | Professor J. Prioetto |
Scheme | UMOSG Grant |
Role | Investigator |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20063 grants / $2,105,000
NHMRC Clinical Centre for Research and Excellence in Clinical Science in Diabetes$2,000,000
Funding body: National Health & Medical Research Council
Funding body | National Health & Medical Research Council |
---|---|
Project Team | Prof. J. Best |
Scheme | Discovery project |
Role | Investigator |
Funding Start | 2006 |
Funding Finish | 2006 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
Investigation of peripheral blood monocyte and adipose tissue macrophage function in obese subjects undertaking bariatric surgery$55,000
Funding body: Pfizer (USA)
Funding body | Pfizer (USA) |
---|---|
Scheme | Award |
Role | Lead |
Funding Start | 2006 |
Funding Finish | 2006 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
The role of the macrophage in Type 2 diabetes$50,000
Funding body: Royal Australasian College of Physicians
Funding body | Royal Australasian College of Physicians |
---|---|
Scheme | Research Establishment Award |
Role | Lead |
Funding Start | 2006 |
Funding Finish | 2006 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20052 grants / $82,000
Melbourne University Early Career Grant$74,000
Funding body: The University of Melbourne Early Career Researcher Grant
Funding body | The University of Melbourne Early Career Researcher Grant |
---|---|
Scheme | The internal grant of the University of Melbourne |
Role | Lead |
Funding Start | 2005 |
Funding Finish | 2006 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
The role of the macrophage in the pathophysiology of diabetic and hypertensive cardiorenal disease$8,000
Funding body: St Vincent's Hospital Sydney
Funding body | St Vincent's Hospital Sydney |
---|---|
Scheme | Pilot Projects |
Role | Lead |
Funding Start | 2005 |
Funding Finish | 2005 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20032 grants / $16,000
Australasian College of Clinical and Experimental Pharmacologists and Toxicologists Travel Prize$10,000
Funding body: Australasian College of Clinical and Experimental Pharmacologists and Toxicologists
Funding body | Australasian College of Clinical and Experimental Pharmacologists and Toxicologists |
---|---|
Scheme | Travel Grant |
Role | Lead |
Funding Start | 2003 |
Funding Finish | 2003 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
CSANZ Travelling Fellowship$6,000
Funding body: Cardiac Society of Australia and NewZealand
Funding body | Cardiac Society of Australia and NewZealand |
---|---|
Scheme | Travelling Fellowship |
Role | Lead |
Funding Start | 2003 |
Funding Finish | 2003 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
20011 grants / $55,000
Cardio Vascular Lipid (CVL) Research Grant$55,000
Funding body: National Heart Foundation of Australia
Funding body | National Heart Foundation of Australia |
---|---|
Scheme | Research Grant |
Role | Lead |
Funding Start | 2001 |
Funding Finish | 2001 |
GNo | |
Type Of Funding | Not Known |
Category | UNKN |
UON | N |
19991 grants / $10,000
Cytochrome P450 2C9 genotype as a predictor for risk of peptic ulcer formation and complications with non-steroidal anti-inflammatory drugs$10,000
Funding body: Christchurch Medical Research Foundation
Funding body | Christchurch Medical Research Foundation |
---|---|
Scheme | Discovery Project |
Role | Investigator |
Funding Start | 1999 |
Funding Finish | 1999 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2023 | PhD | Dosing of 5-Fluorouracil in Colorectal Cancer | PhD (Medicine), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2022 | PhD | Australian Patient Centred Clinical Model For Improved Health Outcomes Using Cannabidiol – PACIFIC Study | PhD (Clinical Pharm), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2021 | PhD | Over-Prescription of Opioid Analgesics on Discharge after Common General Surgical Procedures | PhD (Surgical Science), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2012 | PhD | Helping students structure knowledge for clinical use in PBL | Pharmacology, University of Queensland | Consultant Supervisor |
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2020 | PhD |
New Analytical Techniques for Determining Pharmacokinetics of Drugs in Neonates PhD now complete |
PhD (Clinical Pharm), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2019 | PhD | QT Prolongation in Mental Health Patients: Contributory Factors and Clinical Significance | PhD (Clinical Pharm), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2019 | PhD | Development of Methods for the Detection of Novel Psychoactive Substances in Oral Fluid | PhD (Clinical Pharm), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2019 | PhD | How pharmacometrics can assist in the personalised dosing of Voriconazole. | Pharmacology, University of Queensland | Co-Supervisor |
2019 | PhD |
Dosing paracetemol in patients with chronic liver disease PhD completed and awarded (UQ) |
Pharmacology, The University of Queensland | Principal Supervisor |
2018 | PhD | Metabolic profiling of plasma and urine in obese population using non-targeted LCMSMS. | Pharmacology, University of Queensland | Co-Supervisor |
2017 | Masters | Flucloxacillin concentrations and outcomes in MRSA septicaemia | Pharmacology, UNSW | Co-Supervisor |
2016 | Masters | Pharmacovigilance of immunology medications | Pharmacology, University of Queensland | Co-Supervisor |
2016 | Masters |
Combined pharmacogenetics and kinetics in hematology First class Honours, runner up for the British Journal of Clinical Pharmacology researcher prize 2016. |
Pharmacology, University of Queensland | Co-Supervisor |
2014 | PhD | Combined effect of diabetes and obesity on survival in cancer | Pharmacology, University of Queensland | Co-Supervisor |
2014 | PhD | Disparities in breast cancer stage at diagnosis in urban and rural adult women: a systematic review and meta-analysis | Epidemiology, The University of Queensland | Co-Supervisor |
2014 | PhD | Effect of obesity on mortality in breast cancer | Pharmacology, University of Queensland | Principal Supervisor |
2014 | PhD | The role of resveratrol, a polyphenolic compound found in red grape skin, in the management of non-alcoholic fatty liver disease | Pharmacology, University of Queensland | Co-Supervisor |
2013 | Honours | Weight based tacrolimus trough concentrations post liver transplant | Pharmacology, The University of Queensland | Principal Supervisor |
2012 | Honours | Relationship of body size to immunosuppressant concentrations and outcomes in liver transplant recipients | Pharmacology, The University of Queensland | Principal Supervisor |
2012 | PhD | Association of Imaging Markers of Myocardial Fibrosis With Metabolic and Functional Disturbances in Early Diabetic Cardiomyopathy | Internal Medicine, University of Queensland | Co-Supervisor |
2011 | Honours | Descriptive study on body size and chemotherapy dose and clinical outcome in a Queensland tertiary Hospital | Pharmacology, The University of Queensland | Principal Supervisor |
2011 | Honours | Effect of changing digoxin instruments and calibration on clinical decision making | Pharmacology, The University of Queensland | Principal Supervisor |
2011 | Honours | Appropriateness of first dose of gentamicin therapy in obese people with sepsis | Pharmacology, The University of Queensland | Principal Supervisor |
2011 | Honours | Descriptive study on body size and chemotherapy dose and clinical outcome in a Queensland tertiary Hospital | Pharmacology, The University of Queensland | Principal Supervisor |
2011 | Honours | Are our obese women with breast cancer receiving suboptimal therapy due to inappropriate estimations of body size | Pharmacology, The University of Queensland | Principal Supervisor |
2009 | PhD | Adiponectin- role in modulating postprandial inflammatory, oxidative and cardiovascular stress | Internal Medicine, University of Queensland | Co-Supervisor |
2009 | Honours | Effect of TDM service on gentamicin dosing | Pharmacology, The University of Melbourne | Principal Supervisor |
2007 | Honours | Tubulointerstitial injury in advanced experimental diabetic nephropathy | Pharmacology, The University of Melbourne | Co-Supervisor |
Research Collaborations
The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.
Country | Count of Publications | |
---|---|---|
Australia | 346 | |
United States | 39 | |
United Kingdom | 38 | |
Canada | 15 | |
China | 15 | |
More... |
News
News • 16 Oct 2020
Professor Jennifer Martin inducted into Australian Academy of Health and Medical Sciences
Professor Jennifer Martin (FRACP, PhD) is being inducted into the Australian Academy of Health and Medical Sciences as a Fellow this week in recognition of her contribution made to health and medical research in Australia, in the area of clinical pharmacology research and education and clinical medicine.
News • 24 Jan 2020
Sharing knowledge in Stockholm
On a recent trip to Europe, Professor Jennifer Martin had the opportunity to present on her medicinal cannabis research to Professor Claes Hultling and the team at The Spinalis Foundation and The Karolinska Institute.
News • 30 Oct 2019
University of Newcastle part of ground-breaking NSW study to grow medicinal cannabis industry
The NSW Government is investing in pioneering research into the medicinal cannabis industry, with Minister for Agriculture, Adam Marshall unveiling a new $10 million study from a top-secret cannabis research facility in regional NSW, last week.
News • 2 May 2019
Australia building the evidence base on medical cannabinoids
News • 15 Nov 2018
Million dollar award night for Hunter medical researchers
Young researchers scooped the pool at the 2018 HMRI Awards Night as more than 30 new grants exceeding $1 million in total, along with three major annual awards, were announced for vital health and medical research projects.
News • 2 Aug 2018
Yes we cannabis?
News • 28 Mar 2018
$1.96 million to personalise cancer treatment and change patient lives
University of Newcastle’s (UON) Professor Jennifer Martin has received $1.96 million in Cancer Council NSW research funding to develop a personalised chemotherapy dosing system for cancer patients to improve quality of life, reduce side effects and increase chance of survival.
News • 23 Nov 2017
NSW Government provides additional $3m to medicinal cannabis research
The NSW Government has announced it will provide more than $3m in funding for medicinal cannabis research to the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), based at the University of Newcastle (UON).
News • 11 Oct 2017
UON researchers shine in 2017 NHMRC funding
University of Newcastle researchers have secured more than $6 million in the latest round of National Health and Medical Research Council (NHMRC) funding, including almost $2.5 million for a world-first research centre to test the effectiveness and safety around medicinal applications of a range of cannabinoids.
News • 24 Feb 2017
ABC News: Who can get medical marijuana
This ABC News analysis explores the impact of the Federal Government's February 2017 approval of the importation of medicinal marijuana.
News • 30 May 2016
More to do before medicinal cannabis rollout
While there has been significant progress towards the mainstream use of medicinal cannabis over the past year, there are a number of missing links that need to be examined before it is rolled out as a therapeutic good, according to the authors of a Perspective published online today by the Medical Journal of Australia.
News • 23 Feb 2016
ABC 7.30: Potentially deadly and illegal synthetic drugs still available over the counter
Professor Jenny Martin and Michelle Williams are researchers in Clinical Phamacology and Toxicology at the University of Newcastle. They were recently featured on ABC's 7.30 explaining the dangers of illegal synthetic drugs, some of the surprising ingredients, and why one dose can be fatal.
News • 28 Jul 2015
University of Newcastle researchers commence Medical Cannabis Trials
University of Newcastle researchers will undertake critical research as part of Australia's first medical cannabis trial, announced this morning by Premier Mike Baird and Minister for Medical Research Pru Goward.
Professor Jennifer Martin
Position
Chair of Clinical Pharmacology
School of Medicine and Public Health
School of Medicine and Public Health
College of Health, Medicine and Wellbeing
Contact Details
jen.martin@newcastle.edu.au | |
Phone | (02) 4042 0851 |
Fax | (02) 4960 2088 |
Office
Building | Hunter Medical Research Institute (HMRI) |
---|---|
Location | HMRI 3 West Lot 1 Kookaburra Circuit New Lambton Heights NSW 2305 , |