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In the original publication, Page 3, Sect. 4.3, the first sentence was incorrectly published.

Nurses', respiratory therapists' (RTs), and physicians' concerns about oxygen weaning practices and pulse oximetry use in healthy children during inpatient admissions prompted this multidisciplinary evidence-based project. A nurse-led inter-professional team found lack of consistent oxygen weaning practices and lack of guidelines for nurses or RTs regarding pulse oximetry use with children admitted for acute respiratory illness. The team created and piloted evidence-based oxygen weaning and pulse oximetry protocols. After a 6 month pilot, children in the pilot had shorter length of stay, time on oxygen, and time on continuous pulse oximetry. Protocols improved patient outcomes and decreased associated charges.

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.

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.

HLA-A*33:01 is strongly associated with drug-induced liver injury (DILI) due to terbinafine and several other unrelated compounds

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). 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). Indigenous women were more likely to be socially disadvantaged (43 vs. 20 %, p

As the world's population ages, global health care systems will face the burden of chronic diseases and polypharmacy use among older adults. The traditional tasks of medication dispensing and provision of basic education by pharmacists have evolved to active engagement in direct patient care and collaborative team-based care. The care of older patients is an especially fitting mission for pharmacists, since the key to geriatric care often lies with management of chronic diseases and polypharmacy use, and preventing harmful consequences of both. Because most chronic conditions are treated with medications, pharmacists, with their extensive training in pharmacotherapy and pharmacokinetics, are in a unique and critical position in the management of them. Pharmacists have the expertise to detect, resolve, and prevent medication errors and drug-related problems, such as overtreatment, undertreatment, adverse drug events, and nonadherence. Pharmacists are also competent in critically reviewing and applying clinical guidelines to the care of individual patients, and in some instances confront the lack of data (common in older adults) to provide the best possible patient-centered care. The current review aimed to depict the evidence of geriatric pharmacy care, demonstrate current impact of pharmacists' interventions on older patients, survey the tools used by pharmacists to provide effective care, and explore their role in pharmacotherapy optimization in elders. The findings of the current review strongly support previous studies that showed positive impact of pharmacists' interventions on older patients' health-related outcomes. There is a clear role for pharmacists working directly or collaboratively to improve medication use and management in older populations. Therefore, in global health care systems, teams caring for elders should involve pharmacists to optimize pharmacotherapy.

Free to read on journal website (may need to create free account first) Objectives To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy. Design Prospective cohort study. Participants and setting Patients aged 70 years or older admitted to general medical units of 11 acute care hospitals in two Australian states between July 2005 and May 2010. All patients were assessed using the interRAI assessment system for acute care. Main outcome measures Measures of physical, cognitive and psychosocial functioning; and number of regular prescribed medications categorised into three groups: non-polypharmacy (0–4 drugs), polypharmacy (5–9 drugs) and hyperpolypharmacy (≥ 10 drugs). Results Of 1220 patients who were recruited for the study, medication records at admission were available for 1216. Mean age was 81.3 years (SD, 6.8 years), and 659 patients (54.2%) were women. For the 1187 patients with complete medication records on admission and discharge, there was a small but statistically significant increase in mean number of regular medications per day between admission and discharge (7.1 v 7.6), while the prevalence of medications such as statins (459 [38.7%] v 457 [38.5%] patients), opioid analgesics (155 [13.1%] v 166 [14.0%] patients), antipsychotics (59 [5.0%] v 65 [5.5%] patients) and benzodiazepines (122 [10.3%] v 135 [11.4%] patients) did not change significantly. Being in a higher polypharmacy category was significantly associated with increase in comorbidities (odds ratio [OR], 1.27; 95% CI, 1.20–1.34), presence of pain (OR, 1.31; 1.05–1.64), dyspnoea (OR, 1.64; 1.30–2.07) and dependence in terms of instrumental activities of daily living (OR, 1.70; 1.20–2.41). Hyperpolypharmacy was observed in 290/1216 patients (23.8%) at admission and 336/1187 patients (28.3%) on discharge, and the proportion of preventive medication in the hyperpolypharmacy category at both points in time remained high (1209/3371 [35.9%] at admission v 1508/4117 [36.6%] at discharge). Conclusions Polypharmacy is common among older people admitted to general medical units of Australian hospitals, with no clinically meaningful change to the number or classification (symptom control, prevention or both) of drugs made by treating physicians.

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.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.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%, P0.001). 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]).Improving the early diagnosis of cervical cancer in Indigenous women may increase cancer-specific survival in the year following diagnosis.

A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin concentrations by 10%. The assay was recalibrated by the manufacturer in 2010, but clinical outcomes of the underestimation were never measured. This is a pilot study to describe the prescribing behavior around out-of-range digoxin concentrations and to assess whether miscalibrated digoxin immunoassays contribute to clinically relevant effects, as measured by inappropriate alterations in digoxin doses. About 30,000 digoxin concentrations across the State Hospital system were obtained in 2 periods before and after recalibration of the digoxin assay. Digoxin concentration means were calculated and compared and were statistically significantly different. Subsequently, a single-centered retrospective review of 50 randomly chosen charts was undertaken to study the clinical implications of the underestimated concentrations. Mean digoxin concentrations for 2009 and 2011 were significantly different by 8.8% (confidence interval, 7.0%-10.6%). After recalculating the 2009 concentrations to their "corrected" values, there was a 16% increase in the number of concentrations within the range when compared with the 2011 concentrations (41.48% versus 48.04%). However, overall, this did not cause unnecessary dose changes in patients who were "borderline" or outside the therapeutic range when compared with controls (P = 0.10). The majority of decisions were based on the clinical impression rather than concentration alone (85.1% versus 14.9%), even when the concentration was outside the "therapeutic range." Although recalculating digoxin concentrations measured during 2009 to their corrected values produced a significant change in concentration and values inside and outside the range, this does not seem to have had an influence on patient treatment. Rather, clinicians tended to use the clinical impression to dose digoxin.

Cultivation of cannabis for medicinal or scientific purposes needs considered management before it is rolled out as a therapeutic good. Since the publication in the Journal last year of a perspective on cannabis that stated: “Australia is behind the times on the medicinal use of cannabis”, there appears to have been a palpable change in community attitudes around cannabis as medicine. This has occurred alongside anecdotal reports from people with intractable illnesses who have had symptomatic benefit with cannabis. Palliative care specialists have acknowledged a potential role for medicinal cannabis in their specialty. Internationally, the scene is also changing. For example, the Netherlands Office of Medicinal Cannabis enables dispensation through pharmacies after purchase from a contracted company, which also exports to other European countries. In the United States, 23 states and Washington, DC, have legalised marijuana in some form, mostly for medicinal purposes, since June 2015.

© La Trobe University 2018. 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.

Background: Medicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion. Case description: A cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12 g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission. Results: THC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ∼60 ng/mL. Evidence suggests that blood THC concentrations > 5 ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop < 5 ng/mL was 49 days after administration. Discussion: The unusual pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy Refereed/Peer-reviewed

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.

SummaryBackground Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Introduction: 5-Fluorouracil is a commonly prescribed antineoplastic drug. Historically, methods to determine this compound in biological fluids have been time consuming or not sensitive enough.

The issue of tailored dosing adjusted according to a range of patient-specific factors other than bodyweight or body surface area is of large and increasing clinical and financial concern. Even if it is known that dosing alterations are likely to be required for parameters such as body composition, gender and pharmacogenetics, the amount of dosing change is unknown. Thus, pharmacokinetically guided dosing is making a resurgence, particularly in areas of medicine where there are cost constraints or safety issues, such as in haematology medications. However, the evidence to support the behaviour is minimal, particularly when long-term outcomes are considered. In haematology, there are particular issues around efficacy, toxicity and overall cost. Newer targeted agents, such as the monoclonal antibody rituximab and the tyrosine kinase inhibitor imatinib, whilst clearly being highly effective, are dosed on a milligram per square metre (rituximab) or fixed dose basis (imatinib), regardless of body composition, tumour aspects or comorbidity. This review questions this practice and raises important clinical issues; specifically, the clinical potential for combined pharmacokinetically and pharmacodynamically guided dosing of new targeted agents in haematological malignancies. This pharmacokinetically and pharmacodynamically guided dosing is an emerging area of clinical pharmacology, driven predominantly by toxicity, efficacy and cost issues, but also because reasonable outcomes are being noted with more appropriately dosed older medications adjusted for patient-specific factors. Clinical trials to investigate the optimization of rituximab dose scheduling are required.

The use of recombinant human erythropoietin (rhEPO) to promote repair and minimize cardiac hypertrophy after myocardial infarction has had disappointing outcomes in clinical trials. We hypothesized that the beneficial non-hematopoietic effects of rhEPO against cardiac hypertrophy could be offset by the molecular changes initiated by rhEPO itself, leading to rhEPO resistance or maladaptive hypertrophy. This hypothesis was investigated using an isoproterenol-induced model of myocardial infarct and cardiac remodelling with emphasis on hypertrophy. In h9c2 cardiomyocytes, rhEPO decreased isoproterenol-induced hypertrophy, and the expression of the pro-fibrotic factors fibronectin, alpha smooth muscle actin and transforming growth factor beta-1 (TGF-β1). In contrast, by itself, rhEPO increased the expression of fibronectin and TGF-β1. Exogenous TGF-β1 induced a significant increase in hypertrophy, which was further potentiated by rhEPO. Exogenous fibronectin not only induced hypertrophy of cardiomyocytes, but also conferred resistance to rhEPO treatment. Based on these findings we propose that the outcome of rhEPO treatment for myocardial infarction is determined by the baseline concentrations of fibronectin and TGF-β1. If endogenous fibronectin or TGF-β levels are above a certain threshold, they could cause resistance to rhEPO therapy and enhancement of cardiac hypertrophy, respectively, leading to maladaptive hypertrophy.

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 (50 mm × 3 mm × 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.

The failure to reach target doses of heart failure drugs reported in the study by Greene et al. [(1)][1] has been observed in many audits. The relatively marginal benefit and increased risks of higher doses, particularly in combination therapy, may not convince some clinicians. Maximum approved

Cancer patients who have transitioned from curative intent chemotherapy or radiotherapy to palliative therapy have limited life expectancies. Due to this, medications for primary and secondary prevention or those with no short-term benefit are potentially inappropriate medicines in this patient group. These medications often have potentially harmful profiles, increasing the patient’s adverse drug events, pill burden, and medication costs. This review evaluates the most current evidence to assess the outcomes and potential methods used for identifying and ceasing potentially inappropriate medications (PIMs) in palliative cancer patients. A systematic review of the literature was conducted using the databases Ovid MEDLINE, PubMed, EMBASE, IPA, and CINAHL. Of the 51 articles examined in detail, three studies relating to cancer have been evaluated. In these retrospective and cross-sectional studies, the incidence of PIMs was shown in approximately 20 % of patients, although the studies were inconsistent. In addition, six studies were identified that demonstrated the evidence in other population groups; these studies have been selected to establish the evidence in large-scale retrospective studies, prospective cross-sectional studies, both demonstrating the prevalence of PIMs, as well as the outcomes of ceasing PIMs. There is evidence that PIMs are commonly prescribed in palliative care patients. There are no studies that have identified the impact of ceasing PIMS in this setting. Published tools and implemented strategies have focused on the elderly populations. Further research is warranted in establishing clear guidelines for the identification of PIMs in palliative cancer patients as well as interventional studies assessing the outcomes of ceasing PIMs in these patients.

The excitement surrounding the newly redefined concept of ‘Personalized medicine’ was ignited in the Wall Street Journal in 1999. This heralded a ‘New Era of Personalized Medicine’ to ‘target drugs for each unique genetic profile’ 1, spurred on by an era of apparently targeted therapies. Today, personalized medicine has been redefined to ‘Precision medicine’ to incorporate genomics and aimed at developing new targets, treatments and optimized therapy. Ideally, the clinician's concept of personalized medicine is about the right drug, dose, patient and time. Additionally it involves basic principles of pharmacological and clinical medicine. Although personalized medicine embodies the culture of clinical pharmacology, this Editorial alerts to the paradox that lack of the input of clinical pharmacology into personalized medicine has led to incomplete translation of genomic data into the optimal choice and application of cancer drugs and the funding decisions of public access to therapies.

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. Refereed/Peer-reviewed

Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Background: Overcrowding and prolonged length of stay in emergency departments (ED) are increasing problems in hospitals. Rapid availability of all laboratory results has an impact on clinical decision-making, admissions or discharge decisions and resource utilisation. Increasing number of our urinary drugs of abuse (DOA) screens had a turnaround time (TAT) of up to 33 days after the discharge of the patient. Materials and methods: Following an audit and a consultation period with clinicians using the service, a policy change was implemented to reduce the use of gas chromatography mass spectroscopy (GCMS): all requests would have a standard immunoassay (IA) test panel undertaken unless specifically they requested GCMS (including medico-legal) analysis. Results: Almost all of the clinicians interviewed had no understanding of the DOA screening or the difference in the information generated between a confirmatory GCMS urine toxicology screen and IA DOA panel. It appeared none of the patients surveyed in the audit would have had a different clinical decision made if a GCMS had not been undertaken. Post change audit showed only 4.3% of drug requests for IA also received a confirmatory GCMS testing. The estimated saving post change implementation was $127,000 (AU $) in test costs alone over a two year period. The TAT of GCMS results was reduced to 3–4 days. Conclusion: A laboratory-led behavioural change in test requesting is possible and sustainable provided the reason is clinically sound and accompanied by consultation and availability of advice by phone when requested on test requesting or interpretation.

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.

This article examines an embedded librarian program eight years after implementation in a large academic health center. Librarians were physically moved into the colleges of pharmacy, public health, and nursing. Statistics are reported as well as comments from the participating librarians and faculty members. Strong relationships have been built between librarians, faculty members, and students. Locating the librarians among faculty and students led to a better understanding of client needs and an increased awareness of librarian competencies and services resulting in partnerships and greater utilization of library services.

Objective. To conduct a systematic review of reports of pharmacy student research programs that describes the programs and resulting publications or presentations. Methods. To be eligible for the review, reports had to be in English and indicate that students were required to collect, analyze data, and report or present findings. The outcome variables were extramural posters/presentations and publications. Results. Database searches resulted in identification of 13 reports for 12 programs. Two-thirds were reports of projects required for a course or for graduation, and the remaining third were elective (participation was optional). Extramural posters resulted from 75% of the programs and publications from 67%. Conclusion. Although reporting on the outcomes of student research programs is limited, three-quarters of the programs indicated that extramural presentations, publications, or both resulted from student research. Additional research is needed to identify relevant outcomes of student research programs in pharmacy.

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.

From June 2005 to June 2014 the annual cost of the Pharmaceutical Benefits Scheme (PBS) rose from $6 billion to $9.15 billion. That is an increase of 52% or a growth rate of nearly 6% each year. At the same time the Highly Specialised Drugs and Section 100 programs of the PBS, which subsidise the most expensive drugs, increased by 200% or nearly 23% each year.1 This growth has been largely driven by the arrival of expensive biological therapies, antiviral therapies for HIV and hepatitis C, and a variety of small molecules used to inhibit growth in subsets of various cancers. In Australia, enzyme replacement therapy for lysosomal storage diseases, funded by the separate Life Saving Drugs Program, can cost more than $200 000 per person, per year, for life. However, this therapy is not funded in New Zealand for Fabry disease, the commonest lysosomal storage disease. In 2011 New Zealand paid less than half what Australia spent on medications per capita. This has been achieved by having a capped budget and competitive tendering.2 In Australia there is a need to consider the fourth arm of the National Medicines Policy which aims to provide a consistent and supportive environment for the industry.3 The challenges are many, including knowing whether taxpayers are receiving value for money, funding treatments for our expanding ageing population, predicting long-term outcomes and cost-effectiveness for highly expensive medicines with inadequate long-term trial data. There are also the challenges in justifying extremely costly drugs for a few patients with a rare disease, and finding the funding while not reallocating resources from other areas of health care. Many trials of costly drugs do not provide the information required to make a considered and accurate judgement of their value, particularly if registration or funding is based on phase II or observational data in small numbers of patients. Short-term surrogate end points for lifelong or life-threatening diseases also make the estimates of cost-effectiveness imprecise. For example, many expensive cancer therapies measure time to progression, but cannot quantify overall survival differences as patients in the control arm are often allowed to cross over to the active arm if the cancer progresses.4 Treatments for rare diseases are a great development, but are also difficult to assess because the trials cannot recruit enough patients for long enough to show clear clinical end points. What is the true return on investment? What is lost if a new costly drug is approved? Can one make a considered value judgement if the median survival benefit is a couple of months? A measure used in economic analysis is the quality-adjusted life-year (QALY). One QALY is one year of perfect health. QALYs can standardise the quality and quantity of life across diseases and populations. However they also have problems.5 They are a relatively generic measure seen by some clinicians as lacking the specificity that is required in daily practice. In addition, the weighting system used to compute the QALY is most often calibrated in terms of social preferences sometimes derived in healthy populations rather than patients. Thus there is a reasonably valid belief that the value attached to quality of life may be determined by economists making deductions on assumptions that are not relevant to seriously ill patients. Another challenge is to decide which patients will need treatment. Sofosbuvir is a new efficacious antiviral treatment for hepatitis C. However, it is very expensive, originally costing about US$84 000 for a 12-week course. Is it cost-effective to treat everyone when only a small percentage of patients with persistent hepatitis C infection will develop cirrhosis or hepatocellular cancer? The numbers in different studies vary – one cohort study in Germany followed 1980 women for 25 years. Overt cirrhosis developed in 0.5% and advanced fibrosis developed in 1.5%. Only one patient developed hepatocellular carcinoma.6 After 35 years cirrhosis had only developed in 14% who remained viraemic. Despite these concerns the company marketing sofosbuvir recouped its initial outlay of US$11 billion (to buy this drug from a biotechnology company) in its first year of sales.7 While there may be other benefits that are not yet studied or quantified, for example reduced infection risk and reduced general inflammatory symptoms such as fatigue, they come at a high price. Is it acceptable to delay treatment until the patent expires and generics become available? The benefits in terms of cost savings, and therefore the ability to make the drug available to wider populations as the evidence becomes available, could also be measurable. The pharmaceutical industry is among the most profitable industries in the world.7 While innovation and entrepreneurship must be encouraged, it is impossible to know exactly the cost to develop and bring a new drug to the market. Many breakthroughs have come from government-funded or university-funded basic research.7 ‘Big pharma’ then brings the product to market. In fact pharmaceutical companies’ spending on sales and marketing dwarfs their investment in research and development outlays. The way drugs are registered can influence their cost. Ranibizumab is approved for neovascular macular degeneration. However, it costs 40 times more than bevacizumab which is equally efficacious, but not approved for this indication.8 If only one supplier pays the Therapeutic Goods Administration (TGA) to evaluate an old, off-patent drug, it can charge a fortune if the drug is approved. For example, in 2003 thalidomide cost around $6 per capsule, but now costs approximately $30 per capsule. The Pharmaceutical Benefits Advisory Committee (PBAC) has access to independent pharmacoeconomic expertise to assess submissions for including a drug on the PBS. However, many costly drugs only have a role in Australian public hospitals, and state governments do not fund comprehensive pharmacoeconomic assessments or even clinical pharmacologists for formulary decisions. Deciding whether to add a drug to a hospital formulary is thus problematic, especially as the funding must come out of a capped hospital budget, and relativity assessments such as QALYs are unable to guide decisions. Decisions across Australia are therefore haphazard and access to drugs may be determined by where the patient lives and the quality of the assessment by hospital formulary committees. Drug companies are profit driven, while Australians are looking for the best value for money. What is the way forward? Patents for some expensive biological therapies have expired or will expire in the near future. Biosimilars are mimic molecules of these therapies and potentially offer significant cost savings. However, they are not identical and require careful evaluation before marketing. Guidelines for biosimilar products have been produced.9 There is often much uncertainty about value for money, so post-marketing surveillance is required to assess important clinical outcomes. Unfortunately drug companies are less likely to fund expensive definitive trials once the drug is marketed. Funding for independent assessment is required. Drugs that do not realise their initial promise should be considered for removal from the PBS. Cinacalcet was removed from the PBS after reassessment of its cost-effectiveness.10 The TGA and the PBS charge applicants significant assessment fees and the legal liability for the drug once marketed in Australia remains with the applicant. The TGA and PBS should waive these fees in special circumstances to allow submissions from learned societies. Such circumstances should be limited to older drugs where the indication for their use is cost-effective compared to other drugs and where robust evidence for efficacy and safety exists. This would expedite the listing of new indications for current drugs (currently used off label) and have older, off-patent drugs listed and available. In this setting the liability incurred should rest with the Commonwealth. This would allow, for example, bevacizumab to be used for neovascular macular degeneration and diabetic retinopathy. The cost of medicines may be influenced by factors such as international trade agreements, for example the Trans-Pacific Partnership.11 There may need to be safeguards for patients and taxpayers if such agreements affect access to affordable drugs or delay the availability of generic or biosimilar drugs.12 An electronic national formulary for all Australian hospitals could be beneficial. It could be funded by the Commonwealth and updated regularly by a national formulary committee similar in structure to the PBAC. This would improve decision making and allow uniform access to efficacious and cost-effective drugs for all Australians irrespective of where they live.

Individualised drug dosing has been shown to improve patient outcomes and reduce adverse drug events. One method of individualised medicine is the Bayesian approach, which uses prior information about how the population responds to therapy, to inform clinicians about how a specific individual is responding to their current therapy. This information is then used to make changes to the dose. Studies using a Bayesian approach to adjust drug dosing have shown that clinicians are able to achieve a therapeutic range quicker than standard practice. If concentration is related to a pharmacodynamic end-point, this means that the drug will be more effective, and the side-effects will be minimised. Unfortunately, the software options to assist with Bayesian dosing in Australia are limited. The aims of this article are to demystify the concepts of Bayesian dosing, set the context of the Bayesian approach using reference to other dosing strategies and discuss its benefits over current dosing methods for a number of drugs. The article is targeted to medical and pharmacy clinicians, and there is a practical clinical case to demonstrate how this method could be used in everyday clinical practice.

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. Refereed/Peer-reviewed

The attempt to speed up drug registration approvals could be detrimental for the appropriateness and safety of new medicines in Australia.

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.

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. Refereed/Peer-reviewed

Health-related quality of life (HRQoL) and associated factors were assessed among 155 Indigenous Australian adult cancer patients 6 months post-diagnosis. The Assessment of Quality of Life-4D Questionnaire was used to assess HRQoL. Differences in the median utility score among subgroups of interest were examined using nonparametric tests. Factors associated with excellent HRQoL were assessed through logistic regression. Participants’ mean age was 52 years (range 20–78), and the majority were female (60 %), unemployed (72 %), and recruited from outpatients clinics (64 %). Breast cancer (27 %) was the most common diagnosis. The median HRQoL score was 0.62; 14 % of participants reported excellent HRQoL (>0.90). After adjusting for age, admission status, and treatment, excellent HRQoL was more likely among participants of Torres Strait Islander origin [adjusted odds ratio (AOR) 3.68; 95 % CI 1.23–11.01], those living in regional areas (AOR 5.59; 95 % CI 1.42–22.06), and those whose main language spoken at home was not English (AOR 3.60; 95 % CI 1.08–11.99) and less likely among those reporting less contact with Indigenous people (AOR 0.23; 95 % CI 0.68–0.81). Assessing HRQoL is important to identifying and improving the length and quality of cancer survivorship, especially in groups that have significantly poorer cancer outcomes, such as Indigenous Australians. Acknowledging the study’s observational nature, we found HRQoL was lower than reported for other Australians, and we identified some socio-demographic factors that were associated with excellent HRQoL. Such assessments are an important component of identifying and evaluating appropriate interventions to improve the health and well-being of Indigenous cancer patients.

Purpose: Therapeutic drug monitoring (TDM) is being considered as a tool to individualise sunitinib treatment of gastrointestinal stromal tumours (GIST). Here, we used computer simulations to assess the expected impact of sunitinib TDM on the clinical outcome of patients with GIST. Methods: Monte Carlo simulations were performed in R, based on previously published pharmacokinetic–pharmacodynamic models. Clinical trials with dose-limiting toxicity and patient dropout were simulated to establish the study size required to obtain sufficient statistical power for comparison of TDM-guided and fixed dosing. Results: The simulations revealed that TDM might increase time to tumour progression by about 1–2 months (15–31 %) in eligible patients. However, the number of subjects required for a sufficient statistical power to quantify clinical benefit of TDM guided is likely to be prohibitively high (>1000). Conclusion: Although data from randomised clinical trials on the clinical impact of sunitinib TDM are lacking, our findings support implementation of sunitinib TDM in clinical practice. For rare cancers with well-defined exposure–response relationships, modelling and simulation might allow the optimisation of dosing strategies when clinical trials cannot be performed due to low number of patients. Refereed/Peer-reviewed

Warfarin is a very widely used therapy worldwide, despite newer oral anticoagulants that have become available in some countries during approximately the past 5 years. The reasons for the lower than expected uptake of the newer agents may include cost, excess bleeding risk with dabigatran or need for monitoring in some patients, lack of reversibility for several new anticoagulants, and the high cost of these reversal agents where they exist. The fact that new agents have not been embraced as widely as predicted may suggest that warfarin will remain the mainstay of oral anticoagulant therapy for the near future. Thus, there remains a need to continue research to dose warfarin more safely and effectively. The main complaint with warfarin is the large inter- and intrapatient variability noted in warfarin dosage requirements. Although some variability is related to factors such as gender and age, a large amount of variability is not accounted for; this is likely related to factors such as components of diet, concomitant therapies, and an individual’s bowel flora. To facilitate dosing, a number of algorithms have been made available to support warfarin use. However, such algorithms have usually been unable to take into account possible genetic factors that may contribute to pharmacokinetics and pharmacodynamics of warfarin therapy, thus eventually helping in predicting an individual’s loading and maintenance doses for safer anticoagulation. This chapter discusses the factors known to affect therapeutic anticoagulation with warfarin, including the pharmacogenetic polymorphisms in CYP2C9 and genetic polymorphisms in the C1 subunit of the vitamin K 2,3-epoxide reductase complex. Although pharmacogenomic testing per se is an exciting intellectual possibility, it does not predict all of the variation that is clinically relevant to be part of routine care. However, with more knowledge about the effects of dietary components and incorporation into a model with relevant clinical factors, the knowledge could be very useful in improving efficacy of warfarin therapy.

Background: Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of appropriateness. This study aims to evaluate the appropriateness of prescribing, and significance of omissions, from a doctor pharmacist collaborative prescribing model in an elective surgery pre admission clinic (PAC). Method: A modified version of the Medication Appropriate Index (MAI) was developed, piloted and subsequently used by an expert panel, comprised of a surgeon, anaesthetist, clinical pharmacologist, pharmacist, resident medical officer (RMO) and clinical nurse. The tool was used to rate the appropriateness of prescribing of medications, and the significance of omissions in a 5% sample (N=19) of the total cohort from a randomised, controlled two arm trial of doctor-pharmacist collaborative prescribing. Results: When reviewer assessments were combined, 32 out of 294 (10.9%) medications assessed for appropriateness in the control arm were classed as inappropriate, compared to 13 of 266 (4.9%) in the intervention arm. Out of 89 regular medications in the control arm, 25 (28%) were omitted from the medication charts, compared to 1 out of 55 (2%) in the intervention arm (p