ORCID Profile
0000-0002-8614-0199
Current Organisation
University of Newcastle Faculty of Health
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Publisher: Springer Science and Business Media LLC
Date: 16-04-2016
DOI: 10.1007/S40262-016-0394-3
Abstract: 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/m(2) 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 in idualisation of tyrosine kinase inhibitor administration are now emerging. Evidence suggests there is not a clear relationship of a single dose to maximum plasma concentration (C max), steady-state trough concentration (C trough) or area under the curve (AUC). Furthermore, a significant number of questions remain related to the specific timing and frequency of s le 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 s ling 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 s le size are highly recommended to ensure enough patients are s led to be sure of a clinical benefit from this concentration-directed methodology.
Publisher: Springer Science and Business Media LLC
Date: 2003
DOI: 10.2165/00002018-200326010-00002
Abstract: The present review outlines the clinical relevance of pharmacokinetic drug interactions within the HMG-CoA reductase inhibitor class. These interactions can result in markedly increased or decreased plasma concentrations of some drugs within this class. However, the relationship between altered plasma concentrations and adverse effects or toxicity may not be linear. It is likely that other variables affect this concentration-effect relationship including: rapid changes in the concentration, concomitant lipid-lowering therapy or host genetic factors that code for different forms or amounts of metabolising enzymes and drug receptors. It is not currently possible to predict which patients will manifest clinically important drug-drug interactions, nor what concentration of an HMG-CoA reductase inhibitor will cause rhabdomyolysis. Thus, until prescribers have better scientific information from which to develop a 'therapeutic range' for each agent, caution should be exercised. In particular, patients taking a CYP3A4-metabolised agent, e.g. atorvastatin, simvastatin and lovastatin, should not be started on a CYP3A4 inhibitor or inducer without close monitoring.
Publisher: Therapeutic Guidelines Limited
Date: 02-2016
Publisher: Baishideng Publishing Group Inc.
Date: 28-08-2008
Publisher: Wiley
Date: 31-10-2023
DOI: 10.1111/CTS.13664
Publisher: MDPI AG
Date: 25-09-2022
DOI: 10.3390/PH15101186
Abstract: The global burden of cancer necessitates rapid and ongoing development of effective cancer therapies. One promising approach in this context is the repurposing of existing non-cancer drugs for cancer indications. A key to this approach is selecting the cellular targets against which to identify novel repurposed drugs for pre-clinical analysis. Protein kinases are highly sought-after anticancer drug targets since dysregulation of kinases is the hallmark of cancer. To identify potential kinase-targeted drug candidates from the existing portfolio of non-cancer therapeutics, we used combined in silico and in vitro approaches, including ligand-based 3D screening followed by biochemical and cellular assessments. This strategy revealed that the anti-viral drug rilpivirine is an Aurora A kinase inhibitor. In view of previous findings implicating Aurora A kinase in abnormal cell cycle regulation, we also examined the influence of rilpivirine on the growth of T47D breast cancer cells. Herein, we detail the identification of rilpivirine as an Aurora A kinase inhibitor, its molecular basis of inhibitory activity towards this kinase, and its Aurora A-mediated anticancer mechanisms in T47D cells. Our results illustrate the value of integrated in silico and in vitro screening strategies in identifying repurposed drug candidates and provide a scientific basis for further exploring the potential anticancer properties of the anti-viral drug rilpivirine.
Publisher: Wiley
Date: 04-2015
DOI: 10.5694/MJA13.00172
Abstract: To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy. Prospective cohort study. 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. 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). 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). 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.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1007/S11136-016-1233-6
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2014
Publisher: Springer Singapore
Date: 04-05-2017
Publisher: Wiley
Date: 13-12-2016
Abstract: To analyze the subsidized use and reported adverse events of ezetimibe, used to lower cholesterol, in Australia over the 11 years following its inclusion on the Pharmaceutical Benefits Scheme (PBS) in 2004. Pharmacoepidemiological analysis of dispensed prescriptions from Medicare Australia. Adverse event data were obtained from the Therapeutic Goods Administration. Use was measured by the defined daily dose (DDD) per 1000 population per day for each calendar year. Adverse events were counted by organ class system. Total ezetimibe use rose to 8.46 DDD/1000 population/d in the 11 years to 2015. Ezetimibe as a sole active ingredient was the most commonly dispensed formulation followed by the two combination products containing ezetimibe and 40 mg or 80 mg simvastatin. The average yearly increase in utilization was 19% with a 24% annual increase in costs to government (2006-2015) to $169.0 million in 2015. There were substantial differences in ezetimibe use between states, with no relationship to deaths from ischaemic heart disease (IHD) in each jurisdiction. The major reported adverse events were musculoskeletal and connective tissue disorders and gastrointestinal disorders. Ezetimibe use has increased rapidly in Australia since receiving public subsidy. Although the indications for subsidy are very restricted, there appears to have been widespread use, not explained by differential geographical IHD death rates. Latest guidelines still question the value of ezetimibe, so further discussion about whether the public spending on this medication for any potential improvement in population health outcomes is justified.
Publisher: Wiley
Date: 13-11-2020
DOI: 10.1111/JPC.14683
Abstract: 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. 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. 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. 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.
Publisher: Wiley
Date: 06-2010
Publisher: Wiley
Date: 20-04-2022
DOI: 10.1111/EPI.17247
Abstract: Rett syndrome (RTT), commonly caused by methyl‐CpG‐binding protein 2 ( MECP2 ) pathogenic variants, has many comorbidities. Fifty to ninety percent of children with RTT have epilepsy, which is often drug‐resistant. Cannabi arin (CBDV), a non‐hallucinogenic phytocannabinoid, has shown benefit in MECP2 animal models. This phase 1 trial assessed the safety and tolerability of CBDV in female children with RTT and drug‐resistant epilepsy, as well as the effect on mean monthly seizure frequency (MMSF), the electroencephalogram (EEG), and non‐epilepsy comorbid symptoms. Five female children with drug‐resistant epilepsy and a pathogenic MECP2 variant were enrolled. Baseline clinical and laboratory assessments, including monthly seizure frequency, were recorded. CBDV oral solution (50 mg/ml) was prescribed and titrated to 10 mg/kg/day. Data collected included pharmacokinetics, seizure type and frequency, adverse events, EEG, and responses to the Rett Syndrome Behaviour Questionnaire and Rett Syndrome Symptom Severity Index, and were compared to baseline data. All five children reached the maximum CBDV dose of 10 mg/kg/day and had a reduction in MMSF (median = 79% reduction). Three children had MMSF reduction 75%. This corresponded to an overall reduction in seizure frequency from 32 to 7.2 seizures per month. Ninety‐one percent of adverse events were mild or moderate, and none required drug withdrawal. Sixty‐two percent were judged to be unrelated to CBDV. Thirty‐one percent of adverse events were identified as possibly related, of which nearly all were mild, and the remainder were later assessed as RTT symptoms. Hypersomnolence and drooling were identified as related to CBDV. No serious adverse events reported were related to CBDV. No significant change was noted in EEG or non‐epilepsy‐related symptoms of RTT. A dose of 10 mg/kg/day of CBDV is safe and well tolerated in a pediatric RTT cohort and suggests improved seizure control in children with MECP2 ‐related RTT.
Publisher: Springer Science and Business Media LLC
Date: 19-01-2019
DOI: 10.1007/S00406-019-00978-2
Abstract: Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ
Publisher: Wiley
Date: 2019
DOI: 10.1111/IMJ.14043
Abstract: 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 ex le drug exposure is increasingly required. (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. 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 s les, phenotypic and outcome variables were analysed. Trough concentrations were similar between obese and non-obese patients (P > 0.05) at each s ling 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%. 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.
Publisher: Wiley
Date: 22-01-2020
DOI: 10.1111/BCP.14205
Publisher: Wiley
Date: 20-01-2015
DOI: 10.1111/BCP.12385
Publisher: Elsevier BV
Date: 09-2016
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.CGH.2014.02.024
Abstract: 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. 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 cl ), 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. 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. 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.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.WHI.2013.11.005
Abstract: We identified breast screening patterns over time and patterns among women residing in rural and urban areas by sociodemographic factors. This study employs a longitudinal design over 9 years from 2001 on 11,200 women aged 50 to 55 from the Australian Longitudinal Study on Women's Health. Area of residence was defined in accordance with the accessibility remoteness index of Australia Plus. Breast screening measures included mammography utilization, clinical breast examinations (CBE), and breast self-examinations (BSE). Most women had a mammogram in the past 2 years in combination with CBE or BSE or both. Despite poorer access to mammography services, women residing in rural areas had similar mammography screening rates to their urban counterparts. Women residing in rural areas were less likely to have CBEs, but more likely to conduct BSEs. The breast screening behaviors were generally consistent over time. The poorer breast cancer survival among rural women is unlikely to be explained by differences in mammography service use. A substantial proportion of the population may be experiencing overscreening by conducting all three types of breast screening.
Publisher: Wiley
Date: 2014
DOI: 10.1111/IMJ.12331
Publisher: Wiley
Date: 27-10-2021
DOI: 10.1002/PRP2.866
Publisher: Wiley
Date: 09-06-2011
Publisher: Wiley
Date: 15-07-2022
DOI: 10.1002/PRP2.988
Publisher: Wiley
Date: 23-06-2020
DOI: 10.1002/PRP2.620
Publisher: Wiley
Date: 26-10-2023
DOI: 10.1002/PRP2.1147
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.MATURITAS.2016.06.021
Abstract: 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.
Publisher: Elsevier BV
Date: 2020
Publisher: Elsevier
Date: 2007
Publisher: Wiley
Date: 18-11-2021
DOI: 10.1111/BCP.14551
Publisher: BMJ
Date: 08-04-2015
Publisher: Hindawi Limited
Date: 17-05-2017
DOI: 10.1111/ECC.12714
Abstract: Indigenous patient navigator (IPN) programmes show promise in addressing barriers to cancer care and facilitation of patient self-efficacy. The purpose of this paper is to describe and reflect upon the experience of training an IPN and implementation of the intervention in the Australian context with Indigenous cancer patients. Randomised clinical trial might provide the best available evaluation measure of an intervention but caution should be taken in the implementation process. Socio-cultural aspects and training can affect the conduct of this type of intervention. We report here five issues needing consideration prior to implementing such intervention. Specifically: (1) recognition of the collective bonds within Indigenous community and understanding by IPN of the degree of personal assistance perceived as not intrusive by the patient (2) conduct ongoing evaluation of the different role of an IPN involved in this intervention care provider vs. researcher. (3) meaningful engagement develops from a trusting/collaborative relationship between research team and study site staff which may not occur in the study time frame (4) existing skills as well as training provided may not translate in the IPN understanding and aligning with the study objectives/research values (5) recruitment of participants requires innovative and highly flexible strategies to be successful.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2014
DOI: 10.1007/S12032-014-0881-Z
Abstract: The purpose of this study was to compare toxicity rates and types between obese and non-obese women during adjuvant chemotherapy for breast cancer, adjusting for regimen type and received dose. We conducted a retrospective cohort study of 537 women receiving chemotherapy, initially treated between 2007 and 2010 at two tertiary hospitals in Brisbane, Australia. Demographic, chemotherapy and toxicity data were extracted from patient charts and analyzed using multivariate logistic regression. Three hundred and seventy-four women were eligible for inclusion. Obese women (body mass index (BMI) > 30 kg/m(2) mean age 52.58 ± 9.49) were older than non-obese women (BMI ≤ 29.9 kg/m(2) mean age 50.19 ± 11.15, P = 0.05) and had more comorbidities (P < 0.01). After adjustment for potential confounders, obesity was not statistically related to chemotherapy-related admission risk (OR 1.27 95 % CI 0.78-2.09) or febrile neutropenia risk (OR 0.56 95% CI 0.28-1.21). However, obese women received chemotherapy with proportionally lower mean relative dose intensity than non-obese women (94 vs. 97% of reference dose, P = 0.03). Eighteen (15.8%) obese and zero non-obese women (P < 0.01) had their chemotherapy dose capped at an arbitrary body surface area. Compared with non-obese women, obese women receive different chemotherapy regimens and relatively lower chemotherapy doses. There was no significant evidence of increased toxicity among obese women with either full or adjusted chemotherapy doses. Full body surface areas-based dosing appears to be tolerated as well in obese as in lean women.
Publisher: Elsevier
Date: 2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
Publisher: Authorea, Inc.
Date: 27-09-2023
Publisher: Springer Science and Business Media LLC
Date: 02-05-2020
DOI: 10.1007/S00520-019-04821-1
Abstract: 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. 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. 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. 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.
Publisher: Bentham Science Publishers Ltd.
Date: 14-06-2017
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.ANNONC.2019.10.019
Abstract: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. ACTRN12609000665235.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2018
DOI: 10.1007/S00228-018-2567-5
Abstract: 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 ersity of terms compare definitions, classifications, and models describing medication harm and suggest which may be useful in both clinical practice and the research setting. A narrative review of key studies defining and/or classifying medication harm terminology was undertaken. 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. 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.
Publisher: Wiley
Date: 12-2009
Publisher: Therapeutic Guidelines Limited
Date: 06-2016
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/IMJ.13412
Abstract: In idualised drug dosing has been shown to improve patient outcomes and reduce adverse drug events. One method of in idualised medicine is the Bayesian approach, which uses prior information about how the population responds to therapy, to inform clinicians about how a specific in idual 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.
Publisher: Springer Science and Business Media LLC
Date: 10-2008
DOI: 10.1007/S11883-008-0058-3
Abstract: Despite many post hoc analyses of cardiovascular databases in recent years suggesting a benefit of statins in the prevention and treatment of congestive heart failure (HF), a prospective study of statin therapy on two clinically relevant end points--HF morbidity and survival--had not been reported until 2007. However, a large-scale prospective trial, Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA), has just reported its primary results. These results somewhat surprisingly show no survival benefit in a group of patients with ischemic systolic HF given low-dose rosuvastatin. In addition to this uncertainty generated by the results of CORONA, there remains additional uncertainty in the existing, predominantly retrospective data on statins because of the potential bias in study designs, use of post hoc subgroup analyses, and lack of mechanistic data. This review critically evaluates the recent literature in this area.
Publisher: Wiley
Date: 21-03-2021
DOI: 10.1002/PRP2.757
Abstract: 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 in idual dosing and the potential of therapeutic drug monitoring (TDM) to carry out this in idualization. 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.
Publisher: Informa UK Limited
Date: 09-11-2022
DOI: 10.1080/17512433.2022.2142114
Abstract: In light of the widespread use of non-prescribed and prescribed cannabidiol, the use of cannabidiol with other medications is likely, and this may result in drug interactions. We aimed to ascertain if clinical guidance could be provided on the dose range at which cannabidiol drug interactions are likely to occur with concurrently prescribed medicines. Literature searches were conducted in Embase, MEDLINE, and PubMed from database inception to January 2022 using Emtree and MeSH terms. Reference list screening yielded further studies. Using currently available data, likely drug interactions of which prescribers of cannabidiol need to be aware, at the doses likely to cause clinically significant interactions, and drug dosing changes that may be needed are highlighted. We have provided an overview of evidence-based pharmacokinetic predictions and general guidance about the dose range at which clinically relevant cannabidiol drug interactions are likely. For an in idual patient, there are inherent limitations in providing clinical guidance due to gaps in specific drug dose-response data and knowledge of in idual pharmacokinetic profiles, including different co-morbidities, and concurrent medicines. Clinician awareness of cannabinoid pharmacology, along with clinical and therapeutic drug monitoring, are current best practice approaches to manage cannabinoid drug interactions.
Publisher: Wiley
Date: 09-2020
DOI: 10.1111/IMJ.14986
Publisher: Elsevier BV
Date: 09-2002
DOI: 10.1016/S1043-6618(02)00092-0
Abstract: Blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients post-myocardial infarction as well as in chronic heart failure and hypertension. ACE inhibitors also have a well-established place in the treatment of diabetic nephropathy. Angiotensin receptor blockers (ARBs) have been developed to produce a more complete blockade of the actions of angiotensin II as compared to other drug classes, as well as an improved side effect profile. This article provides an overview of the place of ARBs in general and of the ARB valsartan in particular, and draws comparisons to ACE inhibitors in the treatment of cardiovascular diseases.
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/BCP.13695
Publisher: Springer Science and Business Media LLC
Date: 24-08-2012
DOI: 10.1007/S10549-012-2213-3
Abstract: The purpose of this study is to provide more definite evidence regarding the role of dose modification of chemotherapy in obese women with breast cancer by systematically reviewing current literature regarding chemotherapy-induced toxicity rates in obese and non-obese women with early-stage breast cancer. A systematic search of Pubmed and EMBASE was conducted to identify original studies investigating chemotherapy-induced toxicity in obese women receiving adjuvant chemotherapy treatment for breast cancer. Ten studies were identified. We noted low rates of adjustment for confounders such as prophylactic hematopoietic growth factor use and empirical dose reductions. Seven studies found reduced toxicity in obese compared to non-obese women. Of four studies, where dose capping was precluded or statistically adjusted for, three found reduced toxicity in obese women. These outcomes include less febrile neutropenia (body mass index (BMI) >23.6 odds ratio (OR) 4.4 95 % confidence interval (CI) 1.65-12.01), fewer hospital admissions (BMI >35 OR 0.61, 95 % CI 0.38-0.97), and fewer neutropenic events (BMI >25 OR 0.49 95 % CI 0.37-0.66). Only a single study reported higher rates of toxicity in obese women, but this study had significant methodological issues. As a conclusion, we observed that obese patients tolerate chemotherapy better than lean patients. However, this may be confounded by poorly specified dose capping practices and the use of hematopoietic growth factors. Further research should focus on improved documentation of body size, of dose, and of use of growth factors, and analysis of how these affect recurrence rates, toxicity, and survival.
Publisher: Wiley
Date: 23-11-2015
DOI: 10.1111/BCP.12803
Publisher: Wiley
Date: 22-07-2013
DOI: 10.1111/ACER.12143
Abstract: A reliable biomarker is required in hepatology clinics for detection and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin (CDT) increases with sustained heavy alcohol consumption and is the most specific biomarker of ethanol (EtOH) consumption. Recent introduction of a standardized method for measuring CDT has improved its clinical application. This study was designed to determine whether alcohol-independent factors influence CDT levels in patients with chronic liver disease (CLD). The relationship between serum %CDT and self-reported history of alcohol consumption was examined in 254 patients referred for evaluation of liver disease. CDT analysis was performed on serum collected at time of liver biopsy. CDT levels were not affected by severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had a %CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on review of their medical records and clinical results. Conversely, not all acknowledged heavy drinkers had %CDT >1.7. Heavy drinkers with a body mass index (BMI) in the overweight or obese range had significantly lower %CDT than lean heavy drinkers. This persisted even when lean body weight was used as an approximation of the EtOH volume of distribution. An elevated BMI reduces the diagnostic utility of CDT at higher alcohol intake in subjects with CLD using the standardized method. In a hepatology outpatient setting, this assay is likely to be useful to confirm suspicion of heavy drinking in subjects who are not overweight, but cannot reliably identify moderate drinkers or heavy drinkers who are overweight.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2017
DOI: 10.1007/S00520-016-3563-X
Abstract: The purpose of this study was to explore Indigenous Australian cancer survivors' perspectives of follow-up cancer care and management.. This is a qualitative study employing in idual 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. 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. 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 erse 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.
Publisher: Wiley
Date: 25-12-2016
DOI: 10.1111/BCP.12802
Publisher: Wiley
Date: 10-2010
Publisher: Springer Science and Business Media LLC
Date: 07-02-2020
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.2147/IJGM.S96741
Publisher: Wiley
Date: 02-2022
DOI: 10.1002/PRP2.922
Abstract: Why a systems analysis view of this pandemic? The current pandemic has inflicted almost unimaginable grief, sorrow, loss, and terror at a global scale. One of the great ironies with the COVID‐19 pandemic, particularly early on, is counter intuitive. The speed at which specialized basic and clinical sciences described the details of the damage to humans in COVID‐19 disease has been impressive. Equally, the development of vaccines in an amazingly short time interval has been extraordinary. However, what has been less well understood has been the fundamental elements that underpin the progression of COVID‐19 in an in idual and in populations. We have used systems analysis approaches with human physiology and pharmacology to explore the fundamental underpinnings of COVID‐19 disease. Pharmacology powerfully captures the thermodynamic characteristics of molecular binding with an exogenous entity such as a virus and its consequences on the living processes well described by human physiology. Thus, we have documented the passage of SARS‐CoV‐2 from infection of a single cell to species jump, to tropism, variant emergence and widespread population infection. During the course of this review, the recurrent observation was the efficiency and simplicity of one critical function of this virus. The lethality of SARS‐CoV‐2 is due primarily to its ability to possess and use a variable surface for binding to a specific human target with high affinity. This binding liberates Gibbs free energy (GFE) such that it satisfies the criteria for thermodynamic spontaneity. Its binding is the prelude to human host cellular entry and replication by the appropriation of host cell constituent molecules that have been produced with a prior energy investment by the host cell. It is also a binding that permits viral tropism to lead to high levels of distribution across populations with newly formed virions. This thermodynamic spontaneity is repeated endlessly as infection of a single host cell spreads to bystander cells, to tissues, to humans in close proximity and then to global populations. The principal antagonism of this process comes from SARS‐CoV‐2 itself, with its relentless changing of its viral surface configuration, associated with the inevitable emergence of variants better configured to resist immune sequestration and importantly with a greater affinity for the host target and higher infectivity. The great value of this physiological and pharmacological perspective is that it reveals the fundamental thermodynamic underpinnings of SARS‐CoV‐2 infection.
Publisher: Wiley
Date: 07-2019
DOI: 10.1111/IMJ.14415
Abstract: The most important two medicinal cannabinoids are Δ 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 s le of frequent and infrequent cannabis users. 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. 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. 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.
Publisher: MDPI AG
Date: 05-02-2020
Abstract: A number of barriers and challenges must be overcome in order to conduct the pharmacokinetic studies that are urgently needed to inform the selection and dosing of medication in neonates. However, overcoming these barriers can be difficult. This review outlines the common barriers researchers are confronted with, including issues with ethics approval and consent, study design for pharmacokinetic studies and the ability to measure the drug concentrations in the blood s les obtained. Strategies to overcome these challenges are also proposed.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2022
Publisher: Springer Science and Business Media LLC
Date: 07-2014
DOI: 10.1007/S00520-014-2322-0
Abstract: Current data suggests that potentially inappropriate medicines (PIMs) are common in palliative cancer patients however, there is a lack of criteria to assist clinicians in identifying PIMs in these patients. The aims of this study were to design and validate a deprescribing guideline for palliative cancer patients and to undertake a descriptive analysis of the identified PIMs. This prospective, non-interventional cohort study consisted of four major stages: developing an 'OncPal Deprescribing Guideline' from current evidence, the prospective recruitment of consecutive palliative cancer inpatients with an estimated <6-month prognosis, the assessment of all medications to identify PIMs using both a panel of medical experts without access to the guideline as well as a Clinical Pharmacist independently using the OncPal Deprescribing Guideline and the evaluation of the guideline by testing concordance. Descriptive data on the incidence of PIMs identified were also assessed. A total of 61 patients were recruited. The OncPal Deprescribing Guideline matched 94% of 617 medicines to the expert panel with a Kappa value of 0.83 [95% CI (0.76, 0.89)] demonstrating an 'outstanding' concordance. Forty-three (70%) patients were taking at least one PIM, with 21.4% of the total medicines assessed identified as PIMs. The medication-associated cost per patient/month was AUD$26.71. A guideline to assist in the de-escalation of inappropriate medications in palliative cancer patients was developed from current literature. The OncPal Deprescribing Guideline was successfully validated, demonstrating statistically significant concordance with an expert panel. We found that the incidence of PIMs was high in our patient group, demonstrating the potential benefits for the OncPal Deprescribing Guideline in clinical practice.
Publisher: Informa UK Limited
Date: 06-02-2017
DOI: 10.1080/14656566.2017.1285905
Abstract: 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.
Publisher: Wiley
Date: 18-11-2021
DOI: 10.1002/HPJA.556
Abstract: 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. 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. 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. The implementation of recommendations outlined in the OCP framework may help with improving cancer care continuity for Indigenous patients with cancer. 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.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2008
DOI: 10.1007/S10552-008-9249-Z
Abstract: The association between diabetes and cancer incidence has been well documented, but relatively little research has been undertaken on the potential influence of diabetes on cancer survival and the research that is available has produced inconsistent results. Because Indigenous Australians have a high prevalence of diabetes, we assessed survival, stratified by diabetes, among Indigenous Australian cancer patients. We also assessed survival, stratified by diabetes, amongst a cohort of non-Indigenous Australian cancer patients. All-cause survival and cancer-specific survival in diabetic versus non-diabetic cancer patients were assessed in Indigenous and non-Indigenous cohorts separately, using proportional hazards models. Indigenous cancer patients with diabetes (n = 140) had an overall survival disadvantage compared to Indigenous cancer patients without diabetes (n = 675) with all-cause Hazard Ratio (HR) = 1.4 (95% CI 1.1-1.8) adjusted for age, sex, and cancer site. After further adjustment to take into account the greater number of non-cancer deaths and co-morbidities in Indigenous cancer patients with diabetes, and their later stage at cancer diagnosis with less cancer treatment, there was no residual difference in cancer-specific survival compared to Indigenous cancer patients without diabetes (cancer-specific HR = 1.0, 95% CI 0.8, 1.3). Fewer non-Indigenous cancer patients had diabetes (n = 52) and they showed no differences in survival compared to their counterparts without diabetes. The poorer survival of Indigenous Australian cancer patients with diabetes was due to more non-cancer deaths, later stage at cancer diagnosis, less cancer treatment, and more co-morbidities than Indigenous Australian cancer patients without diabetes. In contrast, diabetes did not appear to affect survival in non-Indigenous Australians with cancer, either because there were too few to detect a moderate deleterious effect or because there was no association. Understanding the relation between diabetes and cancer treatment and survival is important because both diabetes and cancer are relatively common diseases, increasingly likely to co-exist.
Publisher: Wiley
Date: 07-2014
DOI: 10.1111/IMJ.12473
Publisher: Springer Science and Business Media LLC
Date: 11-09-2019
DOI: 10.1007/S00228-019-02752-8
Abstract: Anticoagulation-associated adverse drug events are common in hospitalised patients and result in morbidity, mortality, increased length of hospital stay and higher costs of care. Many are preventable. We reviewed the literature to identify and assess interventions intended to improve safety or quality anticoagulant prescribing. A systematic search of EMBASE, MEDLINE, the Cochrane Library, Pretty Darn Quick-Evidence and Health Systems Evidence was undertaken to identify controlled studies assessing system-level interventions to improve prescribing of oral or parenteral therapeutic anticoagulation for any indication in hospitalised adults. Data were extracted for safety and quality outcomes, with studies grouped by intervention type for meta-analysis and narrative review. Of 10,640 records screened, 19 trials evaluating 12,742 participants were included for analysis. No study specifically evaluated prescribing of low molecular weight heparins (LMWHs) or direct acting oral anticoagulants (DOACs). Our findings suggest that physician-led anticoagulation consultation services may reduce bleeding rates in high-risk patients. On meta-analysis, decision supported warfarin dosing resulted in higher proportion of time with international normalised ratio in therapeutic range (p = 0.0007). Studies of other clinical decision support systems and heparin monitoring systems did not demonstrate improved safety, and quality findings were inconsistent. Systematic education and feedback programs were not efficacious. There is currently insufficient high-quality evidence to recommend any reviewed intervention, though several warrant closer evaluation. Adequately powered controlled trials assessing safety outcomes and evidence-based quality markers in high-risk patient groups and studies of interventions to improve safety of LMWH and DOAC prescribing are needed.
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA16.00763
Publisher: Hindawi Limited
Date: 15-05-2001
DOI: 10.1111/ECC.13080
Abstract: This study describes and compares the unmet supportive care needs between Indigenous and Non-Indigenous people with cancer. Data from two cross-sectional supportive care needs studies were matched in a 1:1 ratio for Indigenous (n = 125) and Non-Indigenous (n = 125) Australian adults diagnosed with cancer. Descriptive statistics were used to compare type and prevalence of 24 need items measured by the SCNS-SF34 and SCNAT-IP. A higher proportion of Non-Indigenous participants compared to Indigenous participants reported having any moderate-to-high level of unmet needs (70% vs. 54%, p = 0.013) and the difference was consistently observed across non-matched characteristics. While concerns for caregivers, fear of recurrence and pain were central needs for both Indigenous participants and Non-Indigenous participants, there were some key differences in the specific unmet needs between groups. Physical issues including doing usual daily activities and dealing with fatigue were the top priorities for Non-Indigenous people, while money worries, dealing with psychological issues such as how to keep their spirit strong or hope about their future appeared to be priorities for Indigenous people. Variations in the unmet supportive care needs between Indigenous and Non-Indigenous people with cancer may guide health professionals to target specific needs when preparing care plans.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2010
DOI: 10.1161/CIRCIMAGING.109.934273
Abstract: Limitations in the predictive value of negative exercise echocardiography in type 2 diabetes mellitus has been linked to a reduced end-systolic pressure-volume response (ESPVR). We sought whether abnormal ESPVR reflected subclinical diabetic heart disease by examining the association between the ESPVR and markers of myocardial dysfunction and to establish if the change (Δ) or peak systolic blood pressure/end-systolic left ventricular volume ratio (SP/ESV) is a better marker of contractile reserve in type 2 diabetes mellitus. Resting and exercise echocardiography was performed in 167 apparently healthy patients with type 2 diabetes mellitus (97 men age, 55±10 years) without ischemia, other cardiac disease, or noncardiac complications of diabetes. Standard echocardiographic and color tissue Doppler measures (early diastolic tissue velocity, strain, and strain rate) were acquired at baseline and peak stress in apical long-axis views. Calibrated integrated backscatter was calculated from a resting parasternal long-axis view. ΔSP/ESV was calculated as [(peak stress SP/ESV)−(rest SP/ESV)]. The 83 subjects who demonstrated a ΔSP/ESV ≤12 mm Hg/mL/m 2 after exercise were older and had lower peak heart rate, resting diastolic and stress systolic tissue velocity, stress ejection fraction, and exercise capacity than the remainder. There was no significant association between ΔSP/ESV and metabolic derangement or echocardiographic measures of deformation or backscatter. Change in Sm and stress ejection fraction were independent correlates of ΔSP/ESV. ΔSP/ESV ratio is associated with established features of subclinical diabetic heart disease as well as determinants of contractile reserve (peak hemodynamic response and stress systolic function). Peak ESPVR is poorly associated with markers of myocardial dysfunction.
Publisher: Frontiers Media SA
Date: 25-10-2022
Publisher: Mary Ann Liebert Inc
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 11-09-2018
DOI: 10.1007/S00280-018-3683-8
Abstract: For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics. The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4). Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.
Publisher: AMPCo
Date: 22-08-2019
DOI: 10.5694/MJA2.50324
Publisher: MDPI AG
Date: 15-01-2018
Publisher: Mary Ann Liebert Inc
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 16-12-2015
DOI: 10.1007/S10928-015-9462-9
Abstract: Model based personalised dosing (MBPD) is a sophisticated form of in idualised 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 s ling strategies of limited concentrations from ten richly PK s led 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-03-2019
DOI: 10.1002/HEP4.1334
Abstract: People with decompensated cirrhosis are often prescribed a complex regimen of therapeutic and prophylactic medications. In other chronic diseases, polypharmacy increases the risk of medication misadventure and medication‐related problems (MRPs), with associated increased morbidity, mortality, and health care costs. This study examined MRPs in a cohort of ambulatory patients with a history of decompensated cirrhosis who were enrolled in a randomized controlled trial of a pharmacist‐led, patient‐oriented medication education intervention and assessed the association between MRPs and patient outcomes. A total of 375 MRPs were identified among 57 intervention patients (median, 6.0 interquartile range, 3.5‐8.0 per patient maximum 17). Nonadherence (31.5%) and indication issues (29.1%) were the most prevalent MRP types. The risk of potential harm associated with MRPs was low in 18.9% of instances, medium in 33.1%, and high in 48.0%, as categorized by a clinician panel using a risk matrix tool. Patients had a greater incidence rate of high‐risk MRPs if they had a higher Child‐Pugh score (incidence rate ratio [IRR], 1.31 95% confidence interval [CI], 1.09‐1.56) greater comorbidity burden (IRR, 1.15 95% CI, 1.02‐1.29) and were taking more medications (IRR, 1.12 95% CI, 1.04‐1.22). A total of 221 MRPs (58.9%) were resolved following pharmacist intervention. A greater proportion of high‐risk MRPs were resolved compared to those of low and medium risk (68.9% versus 49.7% P 0.001). During the 12‐month follow‐up period, intervention patients had a lower incidence rate of unplanned admissions compared to usual care (IRR, 0.52 95% CI, 0.30‐0.92). Conclusion : High‐risk MRPs are prevalent among adults with decompensated cirrhosis. Pharmacist intervention facilitated identification and resolution of high‐risk MRPs and was associated with reduced incidence rate of unplanned hospital admissions in this group.
Publisher: American Chemical Society (ACS)
Date: 03-02-2016
Abstract: The development of nonprecious-metal-based electrocatalysts with high oxygen reduction reaction (ORR) activity, low cost, and good durability in both alkaline and acidic media is very important for application of full cells. Herein, we developed a facile and economical strategy to obtain porous core-shell Fe3C embedded nitrogen-doped carbon nanofibers (Fe3C@NCNF-X, where X denotes pyrolysis temperature) by electrospinning of polyvinylidene fluoride (PVDF) and FeCl3 mixture, chemical vapor phase polymerization of pyrrole, and followed by pyrolysis of composite nanofibers at high temperatures. Note that the FeCl3 and polypyrrole acts as precursor for Fe3C core and N-doped carbon shell, respectively. Moreover, PVDF not only plays a role as carbon resources, but also provides porous structures due to hydrogen fluoride exposure originated from thermal decomposition of PVDF. The resultant Fe3C@NCNF-X catalysts, particularly Fe3C@NCNF-900, showed efficient electrocatalytic performance for ORR in both alkaline and acidic solutions, which are attributed to the synergistic effect between Fe3C and N-doped carbon as catalytic active sites, and carbon shell protects Fe3C from leaching out. In addition, the Fe3C@NCNF-X catalyst displayed a better long-term stability, free from methanol crossover and CO-poisoning effects than those of Pt/C, which is of great significance for the design and development of advanced electrocatalysts based on nonprecious metals.
Publisher: AMPCo
Date: 12-2014
DOI: 10.5694/MJA14.00992
Publisher: MDPI AG
Date: 08-2023
DOI: 10.3390/BIOS13080779
Abstract: Microfluidic technology is applied across various research areas including organ-on-chip (OOC) systems. The main material used for microfluidics is polydimethylsiloxane (PDMS), a silicone elastomer material that is biocompatible, transparent, and easy to use for OOC systems with well-defined microstructures. However, PDMS-based OOC systems can absorb hydrophobic and small molecules, making it difficult and erroneous to make quantitative analytical assessments for such compounds. In this paper, we explore the use of a synthetic fluoropolymer, poly(4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole-co-tetrafluoroethylene) (Teflon™ AF 2400), with excellent “non-stick” properties to functionalize OOC systems. Cannabinoids, including cannabidiol (CBD), are classes of hydrophobic compounds with a great potential for the treatment of anxiety, depression, pain, and cancer. By using CBD as a testing compound, we examined and systematically quantified CBD absorption into PDMS by means of an LC-MS/MS analysis. In comparison to the unmodified PDMS microchannels, an increase of approximately 30× in the CBD signal was detected with the fluoropolymer surface modification after 3 h of static incubation. Under perfusion conditions, we observed an increase of nearly 15× in the CBD signals from the surface-modified microchannels than from the unmodified microchannels. Furthermore, we also demonstrated that fluoropolymer-modified microchannels are compatible for culturing hCMEC/D3 endothelial cells and for CBD perfusion experiments.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2009
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/IMJ.14798
Publisher: Wiley
Date: 11-2016
DOI: 10.1111/IMJ.13224
Abstract: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. 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. 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. 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. 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.
Publisher: Portland Press Ltd.
Date: 02-07-2007
DOI: 10.1042/CS20070031
Abstract: HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors (statins) are well-established therapies in the prevention and treatment of cardiovascular disease, reducing all-cause mortality and cardiovascular events in many disease states. Studies have also suggested that statins given to patients after myocardial infarction improve event-free survival even in short time frames however, evidence for the benefit of statins in established HF (heart failure) has not been demonstrated with the same rigour of a randomized clinical trial setting. In fact, clinical data examining the effect of statins in HF have been limited by the retrospective or observational nature of these analyses, examination of incompletely validated surrogate end points, small prospective studies in subgroups of HF subjects, and non-uniform doses and different statins being used. In this review, we examine the evidence for the effect of statins on mortality in HF, taking into account theoretical arguments, appropriateness of surrogate markers, animal data and analysis of the predominantly retrospective clinical data that is currently available.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
Publisher: Wiley
Date: 28-10-2015
DOI: 10.1111/BCP.12690
Publisher: Elsevier BV
Date: 03-2018
Publisher: Wiley
Date: 04-2011
DOI: 10.1111/J.1445-5994.2010.02307.X
Abstract: The Modification of Diet in Renal Disease-derived estimation of glomerular filtration rate (eGFR) is used widely. Although validated in stable chronic kidney disease (CKD) outpatients, it is not known how it performs in those presenting with acute medical illness. We aimed to compare eGFR with Cockroft Gault (CG) - the renal function assessment tool available prior to eGFR - to assess the difference in clinical outcome that would occur when one over another estimation is used in practice. In particular, we wished to assess whether use of eGFR would have resulted in a change of dose of commonly used acutely administered medications. Acute medical admissions presenting to a tertiary hospital between August and December 2008 were included. Serum creatinine concentration, age, sex, height and weight were collected. Renal function was estimated by both estimates. Movement from CKD class 3 to 4 or 5 was measured - a clinically used cut-off point for changes in management. A total of 54 patients was included. eGFR values were higher than those estimated by CG. Almost half of patients categorized as CKD stage 4-5 using CG were only categorized as CKD stage 3 using eGFR. Although we did not use a gold standard estimation of GFR, this study shows that estimates of renal function vary in a clinically significant manner. As estimates of GFR are used to adjust drug dosages and to stratify for many other treatments, it is imperative that we find a method of estimating kidney function that is readily available, consistent and accurate.
Publisher: Wiley
Date: 13-12-2021
DOI: 10.1111/BCP.14512
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CLINTHERA.2017.12.008
Abstract: 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. 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 12g 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. 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 ~60ng/mL. Evidence suggests that blood THC concentrations >5ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop <5ng/mL was 49days after administration. 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.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.AMJMED.2011.09.021
Abstract: The increasing burden of harm resulting from the use of multiple drugs in older patient populations represents a major health problem in developed countries. Approximately 1 in 4 older patients admitted to hospitals are prescribed at least 1 inappropriate medication, and up to 20% of all inpatient deaths are attributable to potentially preventable adverse drug reactions. To minimize this drug-related iatrogenesis, we propose a quality use of medicine framework that comprises 10 sequential steps: 1) ascertain all current medications 2) identify patients at high risk of or experiencing adverse drug reactions 3) estimate life expectancy in high-risk patients 4) define overall care goals in the context of life expectancy 5) define and confirm current indications for ongoing treatment 6) determine the time until benefit for disease-modifying medications 7) estimate the magnitude of benefit versus harm in relation to each medication 8) review the relative utility of different drugs 9) identify drugs that may be discontinued and 10) implement and monitor a drug minimization plan with ongoing reappraisal of drug utility and patient adherence by a single nominated clinician. The framework aims to reduce drug use in older patients to the minimum number of essential drugs, and its utility is demonstrated in reference to a hypothetic case study. Further studies are warranted in validating this framework as a means for assisting clinicians to make more appropriate prescribing decisions in at-risk older patients.
Publisher: Informa UK Limited
Date: 06-03-2018
DOI: 10.1080/15563650.2018.1447119
Abstract: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into "definite", "likely", "possible", or "unlikely" to cause pulmonary arterial hypertension, based on the strength of evidence. This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension. A systematic search was conducted using PubMed covering the period September 1970- 2017. The search term utilized was "drug induced pulmonary hypertension". This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism. Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension. Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection. Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear. Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension. Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports. Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension. Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes. Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects. Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an in idual to PAH have yet to be elucidated.
Publisher: AMPCo
Date: 2017
DOI: 10.5694/MJA16.01157
Publisher: Wiley
Date: 09-10-2017
DOI: 10.1002/EJP.1098
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JCHROMB.2021.123075
Abstract: 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 in idual patients using therapeutic drug monitoring (TDM) has been shown to significantly reduce toxicity and improve cancer outcomes. However, for optimum TDM, s le timing is crucial, along with the need for a venepuncture blood s le to obtain the plasma currently used for 5-FU measurement. In addition to complex blood s le handling requirements, large s le volume and frequent s ling required for pharmacokinetic analysis is another barrier to successfully implementing TDM in a healthcare setting. Micros ling 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 s ling, 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® micros ling devices for s le 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 s le analysis. S les 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 C
Publisher: Springer Science and Business Media LLC
Date: 28-01-2023
DOI: 10.1186/S13148-023-01427-7
Abstract: 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. 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. 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.
Publisher: Wiley
Date: 28-07-2015
DOI: 10.1111/IMJ.12813
Publisher: Therapeutic Guidelines Limited
Date: 10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-12-2018
Publisher: Springer Science and Business Media LLC
Date: 21-12-2014
DOI: 10.1007/S00520-013-2098-7
Abstract: 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.
Publisher: Wiley
Date: 03-2011
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.EJCA.2021.08.033
Abstract: Although therapeutic drug monitoring (TDM) is an important tool in guiding drug dosing for other areas of medicine including infectious diseases, cardiology, psychiatry and transplant medicine, it has not gained wide acceptance in oncology. For imatinib and other tyrosine kinase inhibitors, a flat dosing approach is utilised for management of oral chemotherapy. There are many published studies examining the correlation of blood concentrations with clinical effects of imatinib. The International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) determined that there was a need to examine the published literature regarding utility of TDM in imatinib therapy and to develop consensus guidelines for TDM based on the available data. This article summarises the scientific evidence regarding TDM of imatinib, as well as the consensus guidelines developed by the IATDMCT.
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/IMJ.15635
Abstract: In 2018, an innovative, State government‐funded cannabis medicines drug information service was established for health professionals in New South Wales (NSW). The NSW Cannabis Medicines Advisory Service (CMAS) provides expert clinical guidance and support to medical practitioners considering prescribing a cannabis medicine to their patient(s). This research examines quality assurance and patient outcomes related to enquirers' experience with NSW CMAS. Data collection involved an online, anonymous survey with two components. Following a health professional enquiry, quality assurance data were collected about the enquirers' experience with NSW CMAS. The second survey focussed on patient outcomes and provides real‐world observational data about cannabis medicines safety and effectiveness across a wide range of indications. Data collection occurred between January 2020 and June 2021. Preliminary analyses were based on 68 quality assurance and 50 patient outcomes survey responses. General practitioners represented the highest proportion of survey responses ( n = 33 49%). The most common enquiry involved ‘patient‐specific advice’ ( n = 50 74%). Patient‐specific information provided by the service was mainly used for prescribing decision support ( n = 45 90%). Preliminary findings highlight the impact of an innovative cannabis medicines drug information service in supporting health professional clinical practice in an area of rapid knowledge translation. Quality assurance data indicate that the service is perceived well by the majority of enquirers. Patient outcomes data across a wide range of indications suggest some effectiveness and a reasonable safety profile for prescribed cannabis medicines for most patients.
Publisher: BMJ
Date: 07-11-2013
Abstract: Minimising the harm from inappropriate prescribing in older populations is a major urgent concern for modern healthcare systems. In everyday encounters between prescribers and patients, opportunities should be taken to identify patients at high risk of harm from polypharmacy and reappraise their need for specific drugs. Attempts to reconcile life expectancy, comorbidity burden, care goals and patient preferences with the benefits and harms of medications should be made in every patient at significant risk. Drugs identified by this process of reconciliation as conferring little or no benefit and/or excessive risk of harm should be candidates for discontinuation. Evidence supporting a structured approach to drug discontinuation (or deprescribing) is emerging, and while many barriers to deprescribing exist in routine practice, various enabling strategies can help overcome them.
Publisher: Wiley
Date: 23-01-2023
DOI: 10.1002/PRP2.1057
Publisher: Oxford University Press (OUP)
Date: 11-2007
DOI: 10.1016/J.CARDIORES.2007.06.022
Abstract: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin II in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-beta (p<0.01 compared with non-diabetic Ren-2 rats for all parameters). No significant functional or structural derangements were observed in non-transgenic, SD diabetic rats. These findings indicate that the combination of enhanced tissue renin-angiotensin system and hyperglycaemia lead to the development of diabetic cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine, transforming growth factor-beta, by the diabetic state.
Publisher: Elsevier
Date: 2012
Publisher: American Society of Clinical Oncology (ASCO)
Date: 09-2016
Publisher: Bentham Science Publishers Ltd.
Date: 08-2009
DOI: 10.2174/157339909788920901
Abstract: Diabetes is one of the major causes of morbidity and mortality in the Western world and it currently affects 35 million people in the US alone. Cardiovascular and renal complications of diabetes, Type I and II, account for much of this morbidity, and are now known to be the end result of a complex interplay of pathophysiological processes. These include haemodynamic and metabolic abnormalities such as endothelial dysfunction, inflammation, vasoconstriction, oxidation and fibrosis. For some time it has been difficult to elucidate whether these processes and subsequent dysfunction in organs such as the heart and kidney is due to processes that often coexist with diabetes, such as hypertension. However, it is now clear that there is a distinct pro-inflammatory and pro-fibrotic state in diabetes, which may in addition be complicated by synergistic disease processes. The use of statins in diabetes has been of interest for a while due to the known effect of statins on inflammatory and fibrotic pathways. This review covers the clinical evidence for the use of statins in diabetes, the major known pathophysiological processes that occur in diabetic organ disease and discusses the known and putative effects of statins on these pathways. It concludes with a brief discussion of some early and yet unpublished work regarding the addition of statin therapy to angiotensin inhibition therapy in diabetic disease.
Publisher: MDPI AG
Date: 15-04-2025
DOI: 10.3390/PH14121207
Abstract: Discrepancies between the medicines consumed by patients and those documented in the medical record can affect medication safety. We aimed to characterize medication discrepancies and medication regimen complexity over time in a cohort of outpatients with decompensated cirrhosis, and evaluate the impact of pharmacist-led intervention on discrepancies and patient outcomes. In a randomized-controlled trial (n = 57 intervention and n = 57 usual care participants), medication reconciliation and patient-oriented education delivered over a six-month period was associated with a 45% reduction in the incidence rate of ‘high’ risk discrepancies (IRR = 0.55, 95%CI = 0.31–0.96) compared to usual care. For each additional ‘high’ risk discrepancy at baseline, the odds of having ≥ 1 unplanned medication-related admission during a 12-month follow-up period increased by 25% (adj-OR = 1.25, 95%CI = 0.97–1.63) independently of the Child–Pugh score and a history of variceal bleeding. Among participants with complete follow-up, intervention patients were 3-fold less likely to have an unplanned medication-related admission (adj-OR = 0.27, 95%CI = 0.07–0.97) compared to usual care. There was no association between medication discrepancies and mortality. Medication regimen complexity, frequent changes to the regimen and hepatic encephalopathy were associated with discrepancies. Medication reconciliation may improve medication safety by facilitating communication between patients and clinicians about ‘current’ therapies and identifying potentially inappropriate medicines that may lead to harm.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Hindawi Limited
Date: 26-02-2016
DOI: 10.1111/ECC.12467
Abstract: 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 in idual 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.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2021
DOI: 10.1007/S40122-021-00344-Y
Abstract: 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. 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. 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-in idual 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. 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. Australian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.AMJCARD.2010.10.024
Abstract: Patients with type 2 diabetes mellitus (T2DM) might have subclinical myocardial dysfunction identified at rest or unmasked during exercise. We examined the correlates of the myocardial exercise response in patients with T2DM. Myocardial dysfunction was sought during at rest and exercise echocardiography in 167 healthy patients with T2DM (97 men, 55 ± 10 years). Myocardial ischemia was excluded using stress echocardiography. Standard echocardiography and color tissue Doppler imaging measures (early diastolic tissue velocity [Em], strain, and strain rate) were acquired at baseline and peak stress. The calibrated integrated backscatter was calculated from the at rest parasternal long-axis view. The longitudinal diastolic functional reserve index after exercise was defined as ΔEm [1 - (1/Em(base))]. The clinical, anthropometric, and metabolic data were collected at rest and stress. Subclinical myocardial dysfunction at baseline (n = 24) was independently associated with weight (odds ratio [OR] 1.02, p = 0.04) and hemoglobin A1c (OR 1.36, p = 0.03). This group displayed an impaired exercise response that was independently associated with a reduced exercise capacity (OR 0.84, p = 0.034) and longitudinal diastolic functional reserve index (OR 0.69, p = 0.001). Inducible myocardial dysfunction (stress Em <-9.9 cm/s) was identified after exercise in 70 of the remaining 143 subjects. This finding was associated with calibrated integrated backscatter (OR 1.08, p = 0.04) and lower peak heart rate (OR 0.97, p = 0.002) but not metabolic control. The intensity of the metabolic derangement in patients with T2DM was associated with subclinical at rest myocardial dysfunction, but not with the myocardial exercise response. In conclusion, the association of an abnormal stress response with nonmetabolic factors, including backscatter and blunted peak heart rate, suggests potential roles for myocardial fibrosis and cardiac autonomic neuropathy in patients with nonischemic diabetic heart disease.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2020
DOI: 10.1186/S13063-020-04862-6
Abstract: With cannabis medicines now obtaining legal status in many international jurisdictions (generally on the authorisation of a medical professional), a rapid increase in consumer demand for access to cannabis as a therapeutic option in the treatment and management of a range of indications is being noted. Despite this accessibility, knowledge on optimal use is lacking. Further drug development and clinical trials at regulatory standards are necessary both if a better understanding of the efficacy of cannabis medicines, optimal product formulation and indication-specific dosing is needed and to ensure the broader quality and safety of cannabis medicines in the clinical setting. To enable this, clinical, academic and public calls for the undertaking of rigorous clinical trials to establish an evidence base for the therapeutic use of cannabis medicines have been made internationally. While this commitment to undertake human studies with cannabis medicines is welcomed, it has highlighted unique challenges, notably in the review stages of ethics and governance. This often results in lengthy delays to approval by Human Research Ethics Committees (herein ‘HREC’, Australia’s nomenclature for Institutional Review Boards) and trial commencement. A principal concern in these cases is that in contrast to clinical trials using other more conventional pharmaceutical products, trials of cannabis medicines in humans often involve the use of an investigational product prior to some (or any) of the preclinical and pharmaceutical safety issues being established. This paucity of data around product safety, potential drug interactions, continuity of supply, shelf life and product storage results in apprehension by HRECs and governance bodies to endorse trials using cannabis medicines. This manuscript draws from the experiences of Australian researchers and staff involved in clinical trials of cannabis medicines to describe some of the common difficulties that may be faced in the HREC approval process. It also presents practical advice aimed to assist researchers, HRECs and governance officers navigate this complex terrain. While the authors’ experiences are situated within the Australian setting, many of the barriers described are applicable within the international context and thus, the solutions that have been proposed are typically adaptive for use within other jurisdictions.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2010
DOI: 10.1007/S10549-010-0990-0
Abstract: Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited women diagnosed as recently as 1991. The primary aim of this study was to conduct a meta-analysis that included the more recent studies. A systematic search of MEDLINE, EMBASE and CINAHL was conducted to identify original data evaluating the effects of obesity on survival in newly diagnosed breast cancer patients. Adjusted hazard ratios (HR) from in idual studies were pooled using a random effects model. A series of pre-specified sensitivity analyses were conducted on factors such as overall versus breast cancer survival and treatment versus observational cohort. The meta-analysis included 43 studies that enrolled women diagnosed with breast cancer between 1963 and 2005. S le size ranged from 100 to 424168 (median 1192). The meta-analysis showed poorer survival among obese compared with non-obese women with breast cancer, which was similar for overall (HR = 1.33 95% confidence interval (CI): 1.21, 1.47) and breast cancer specific survival (HR = 1.33 95% CI: 1.19, 1.50). The survival differential varied only slightly, depending on whether body mass index (1.33 1.21, 1.47) or waist-hip ratio (1.31 1.08, 1.58) was used as the measure of obesity. There were larger differences by whether the woman was pre-menopausal (1.47) or post-menopausal (1.22) whether the cohort included women diagnosed before (1.31) or after 1995 (1.49) or whether the women were in a treatment (1.22) or observational cohort (1.36), but none of the differences were statistically significant. Women with breast cancer, who are obese, have poorer survival than women with breast cancer, who are not obese. However, no study has elucidated the causal mechanism and there is currently no evidence that weight loss after diagnosis improves survival. Consequently, there is currently no reason to place the additional burden of weight loss on women already burdened with a diagnosis of cancer. Further research should concentrate on assessing whether factors such as diabetes or type of chemotherapy modify the obesity effect and on understanding the causal mechanism, in particular the role of relative under-dosing.
Publisher: Informa UK Limited
Date: 03-07-2018
DOI: 10.1080/15360288.2018.1545725
Abstract: To examine the laxative prescriptions in hospital inpatients with cancer and non-cancer pain on oxycodone compared to oxycodone plus naloxone combination. Retrospective case note review. A palliative care inpatient unit and a general medical ward in a large tertiary referral hospital. Eighty-four patients receiving oxycodone or combination oxycodone/naloxone on general medical (45 patients) and palliative care wards (39 patients). The primary recorded outcomes were regular opioid dose (milligrams per day) and number of prescribed laxatives (type, doses, and frequency per day). 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. 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.
Publisher: AME Publishing Company
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 07-06-2013
Publisher: Wiley
Date: 12-2016
DOI: 10.1111/IMJ.13247
Abstract: Tumour necrosis factor-alpha inhibitors (anti-TNFα) 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. To describe the off-label use of anti-TNFα and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making. We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFα 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. 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-TNFα (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). This study suggests that anti-TNFα 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.
Publisher: Therapeutic Guidelines Limited
Date: 04-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2010
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.IJCARD.2009.03.098
Abstract: Effect of HMGCoA Reductase Inhibitors on Cardiac Remodelling and Mortality in Rats. Following Hyperglycemia and Myocardial Infarction. The presence of diabetes mellitus (DM) in patients with myocardial infarction (MI) increases mortality, due in part to the presence of known cardiovascular risk factors. However little is known about the impact of DM on cardiac remodelling and on clinical outcomes. We aimed to investigate whether hyperglycaemia may adversely and additionally affect LV remodelling post-MI, and whether the addition of a statin, known to reduce mortality both post MI and in humans with DM, has an effect on these outcomes. Eight week old Sprague-Dawley rats were allocated to 5 groups--control (non-DM)/sham, control-MI, DM-sham, DM-MI and DM-MI with statin gavage (DM-MI/ATV). Echocardiogram and invasive pressure volume analysis were performed prior to sacrifice for estimation of cardiac function. Tissue was analysed for total cardiac collagen, collagen I and III. Hyperglycaemia in the remodelling period significantly increased mortality (70% survival in the C-MI group vs 27% in the DM-MI group), worsened cardiac function and increased fibrosis. All of these variables were attenuated by the addition of a statin. Hyperglycaemia increased mortality in MI and exacerbated LV remodeling, and this was attenuated with statin use. This study confirms the importance of early and intensive treatment of hyperglycaemia in patients with MI and suggests that in humans with both DM and MI the addition of a statin may be beneficial.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/879712
Abstract: 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 .
Publisher: Wiley
Date: 19-03-2019
DOI: 10.1002/CPT.1375
Abstract: 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
Publisher: Wiley
Date: 09-08-2019
DOI: 10.1111/BCP.14050
Publisher: Wiley
Date: 08-03-2022
DOI: 10.1111/BCP.15262
Abstract: There is international interest for consensus advice for prescribers working in the field of drug resistant epilepsy intending to trial potential therapies that are nonregistered or off‐label. Cannabinoids are one such therapy. In 2017, the New South Wales State Government (Australia) set up a cannabinoid prescribing guidance service for a wide variety of indications, based on known pharmacology together with the relevant new literature as it became available. Increasing interest in cannabis medicines use outside this State over the following 5 years together with a paucity of registration‐standard clinical trials, lack of information around dosing issues, drug interactions and biological plausibility meant there remained a large unmet need for such advice. To address the unmet need in epilepsy, and until medicines were registered or regulator quality data were available, it was agreed to bring together a working group comprising paediatric and adult epilepsy specialists, clinical pharmacists., clinical pharmacologists and cannabis researchers from across Australia to develop interim consensus advice for prescribers. Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief. As such it supplements the limited evidence currently available from clinical trials with experience from front‐line practice. It is expected that this consensus advice will be updated as new evidence emerges and will provide guidance for a subsequent Guideline.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.BBRC.2014.01.047
Abstract: 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.
Publisher: Frontiers Media SA
Date: 07-03-2023
Publisher: Wiley
Date: 09-08-2019
DOI: 10.1111/BCP.14057
Publisher: Wiley
Date: 21-01-2016
DOI: 10.1111/AJR.12271
Abstract: To examine urban-rural differences and in idual risk factors for a late stage of breast cancer at diagnosis in Australian women. In idual-level longitudinal data were linked with cancer registry data from New South Wales (New South Wales Cancer Registry linked by the Centre for Health Record Linkage (CHeReL)), Queensland (Queensland Cancer Registry) and Victoria (The Cancer Council Victoria). Participants were drawn from the Australian Longitudinal Study on Women's Health 1946-1951 cohort (n = 13 715). The s le included 195 women identified from the linked cancer registry data with a breast cancer diagnosis. Rural or urban residence was measured using Accessibility/Remoteness Index of Australia Plus (ARIA+). In idual characteristics and socio-demographic variables examined included survey year, menopausal status, country of birth, education and marital status. A late stage of breast cancer at diagnosis was defined based on the TNM Classification of Malignant Tumours. A late stage of breast cancer diagnosis was observed in 36% of women residing in urban areas and 40% of women residing in rural areas. After adjusting for in idual characteristics, we found that obesity was the strongest risk factor for a late stage of breast cancer at diagnosis. Given that women are becoming increasingly obese, and that the rate of obesity is higher in the Australian rural population, this paper provides further evidence for targeting interventions for obesity, particularly in rural Australia, as a public health priority.
Publisher: No publisher found
Date: 2014
DOI: 10.1111/BCP.12318
Publisher: Wiley
Date: 07-2016
DOI: 10.1111/IMJ.13117
Abstract: 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. To describe the current practice in therapeutic anticoagulation in the pregnant population at a tertiary institution. A retrospective study of pregnant women on therapeutic enoxaparin between January 2007 and December 2011. Forty-four pregnant women requiring therapeutic anticoagulation were identified and ided 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/m(2) , 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 in idualised. There were small numbers of toxicity events. 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.
Publisher: Oxford University Press (OUP)
Date: 28-01-2014
DOI: 10.1093/EHJCI/JEU013
Abstract: Subclinical diabetic cardiomyopathy (DCM) is frequent in asymptomatic subjects with type 2 diabetes (T2DM). We sought the response of functional and fibrosis markers to therapy in a trial of aldosterone antagonism for treatment of DCM. Biochemical, anthropometric, and echocardiographic data were measured in 225 subjects with T2DM. Myocardial function was evaluated with standard echocardiography and myocardial deformation ischaemia was excluded by exercise echocardiography. Calibrated integrated backscatter and post-contrast T1 mapping from cardiac magnetic resonance imaging were used to assess myocardial structure. Amino-terminal propeptides of pro-collagen type I (PINP) and III (PIIINP), the carboxy-terminal propeptide of pro-collagen type I (PICP) and transforming growth factor beta-1 were measured from peripheral blood or urine to assess myocardial collagen turnover. Diastolic dysfunction was identified in 81 in iduals, of whom 49 (25 male, age 60 ± 10 years) were randomized to spironolactone 25 mg/day or placebo therapy for 6 months. Groups were well-matched at baseline. Spironolactone therapy was associated with improvements in diastolic filling profile (Δpeak E wave velocity -4 ± 15 vs. 9 ± 10 ms, P = 0.001 ΔE/A ratio -0.1 ± 0.3 vs. 0.2 ± 0.2, P < 0.001) and cIB values (-21.2 ± 4.5 dB vs. -18.0 ± 5.2 dB, P = 0.026 ΔcIB -5.1 ± 6.8 vs. -1.3 ± 5.2, P = 0.030). ΔcIB was independently associated with spironolactone therapy (β = 0.320, P = 0.026) but not Δblood pressure. With intervention, pro-collagen biomarkers (ΔPINP P = 0.92, ΔPICP P = 0.25, ΔPIIINP P = 0.52, and ΔTGF-β1 P = 0.71) and T1 values (P = 0.54) remained similar between groups. Spironolactone-induced changes in myocardial structure and diastolic properties in DCM are small, and are unassociated with changes in collagen biomarkers or T1 values.
Publisher: Wiley
Date: 08-07-2010
DOI: 10.1002/PDS.1969
Abstract: To examine the trends in the prescribing of subsidized proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidized Pharmaceutical Benefits Scheme (PBS). Government data on numbers of subsidized scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Drug utilisation as DDD [defined daily dose]/1000 population/day. The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidized indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines.
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1002/JMRS.103
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
DOI: 10.1097/FTD.0000000000000698
Abstract: 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. 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. 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. 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 (11):2468–2476). In particular, a comprehensive appreciation of its toxicity profile is lacking.
Publisher: SAGE Publications
Date: 28-04-2021
Publisher: AMPCo
Date: 02-2018
DOI: 10.5694/MJA17.01004
Publisher: Wiley
Date: 09-07-2022
DOI: 10.1111/BCP.14964
Abstract: Repurposing the large arsenal of existing non‐cancer drugs is an attractive proposition to expand the clinical pipelines for cancer therapeutics. The earlier successes in repurposing resulted primarily from serendipitous findings, but more recently, drug or target‐centric systematic identification of repurposing opportunities continues to rise. Kinases are one of the most sought‐after anti‐cancer drug targets over the last three decades. There are many non‐cancer approved drugs that can inhibit kinases as “off‐targets” as well as many existing kinase inhibitors that can target new additional kinases in cancer. Identifying cancer‐associated kinase inhibitors through mining commercial drug databases or new kinase targets for existing inhibitors through comprehensive kinome profiling can offer more effective trial‐ready options to rapidly advance drugs for clinical validation. In this review, we argue that drug repurposing is an important approach in modern drug development for cancer therapeutics. We have summarized the advantages of repurposing, the rationale behind this approach together with key barriers and opportunities in cancer drug development. We have also included ex les of non‐cancer drugs that inhibit kinases or are associated with kinase signalling as a basis for their anti‐cancer action.
Publisher: Wiley
Date: 15-01-2021
DOI: 10.1111/BCP.14723
Abstract: Despite advances in targeted cancer therapy, the fluoropyrimidines 5‐fluorouracil (5FU) and capecitabine continue to play an important role in oncology. Historically, dosing of these drugs has been based on body surface area. This approach has been demonstrated to be an imprecise way to determine the optimal dose for a patient. Evidence in the literature has demonstrated that precision dosing approaches, such as DPD enzyme activity testing and, in the case of intravenous 5FU, pharmacokinetic‐guided dosing, can reduce toxicity and yield better patient outcomes. However, despite the evidence, there has not been uniform adoption of these approaches in the clinical setting. When a drug such as 5FU has been used clinically for many decades, it may be difficult to change clinical practice. With the aim of facilitating change of practice, issues and barriers to implementing precision dosing approaches for 5FU and capecitabine are identified and discussed with possible solutions proposed.
Publisher: Wiley
Date: 07-06-2018
DOI: 10.1111/BCP.13635
Publisher: Wiley
Date: 30-10-2016
DOI: 10.1111/BCP.12785
Publisher: Elsevier BV
Date: 10-2002
Abstract: To investigate the nature and extent of the alteration in autonomic function following heterotopic lung transplantation. Measures of cardiac parasympathetic nervous system activity (PNSA) and systemic sympathetic nervous system activity (SNSA) were compared in lung transplant patients and age-matched healthy subjects, both at rest and following autonomic perturbation. Lung transplantation service of a university teaching hospital. Twenty-two lung transplant patients (mean [+/- SEM] age, 50.5 +/- 2.4 years) and 13 healthy subjects (mean age, 48.2 +/- 3.7 years). Lung transplant patients had decreased baseline time and frequency domain measures of heart rate variability compared to healthy subjects (root mean square of successive differences in R-R intervals, 11.2 +/- 1.1 vs 30.3 +/- 4.5 ms, respectively [p < 0.005] LnHP, 2.4 +/- 0.2 vs 4.8 +/- 0.4 ms(2), respectively [p < 0.005]). In addition, lung transplant patients demonstrated an attenuated reduction in LnHP/LnTP following head-up tilt in comparison to healthy subjects (p < 0.05). The baseline recumbent plasma norepinephrine level was increased in lung transplant patients compared to healthy subjects (3.25 +/- 0.43 vs 2.00 +/- 0.27 nmol/L, respectively p < 0.05), and levels increased in both groups with upright head-up tilt. There were no differences between the two groups in heart rate or mean systolic BP responses to both the Valsalva maneuver and cold pressor testing. Lung transplant patients have both reduced PNSA and increased SNSA at rest. Furthermore, these patients appear to have a preserved capacity to respond to autonomic perturbation by increasing SNSA. The mechanisms underlying these observations and their prognostic implications remain to be determined.
Publisher: Elsevier BV
Date: 09-2019
Publisher: Wiley
Date: 2020
DOI: 10.1111/IMJ.14356
Abstract: Cancer care involves many different healthcare providers. Delayed or inaccurate communication between specialists and general practitioners (GP) may negatively affect care. 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. 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. 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. 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.
Publisher: Wiley
Date: 05-2010
DOI: 10.1111/J.1445-5994.2009.01959.X
Abstract: Acidosis is commonly seen in the acute hospital setting, and carries a high mortality. Metformin has been associated with lactic acidosis, but it is unclear how frequently this is a cause of acidosis in hospitalized inpatients. The aim of this study is to explore the underlying comorbidities and acute precipitants of acidosis in the hospital setting, including the relationship between type 2 diabetes (T2DM) and metformin use. Retrospective review. Cases of acidosis were identified using the hospital discharge code for acidosis for a 3-month period: October-December 2005. A total of 101 episodes of acidosis were identified: 29% had isolated respiratory acidosis, 31% had metabolic acidosis and 40% had a mixed respiratory and metabolic acidosis. There were 28 cases of confirmed lactic acidosis. Twenty-nine patients had T2DM, but only five of the subjects with T2DM had lactic acidosis two were on metformin. The major risk factors for development of lactic acidosis were hepatic impairment (OR 33.8, P = 0.01), severe left ventricular dysfunction (OR 25.3, P = 0.074) and impaired renal function (OR 9.7, P = 0.09), but not metformin use. Most cases of metabolic and lactic acidosis in the hospital setting occur in patients not taking metformin. Hepatic, renal and cardiac dysfunction are more important predictors for the development of acidosis.
Publisher: Wiley
Date: 09-2005
DOI: 10.1111/J.1440-1681.2005.04256.X
Abstract: 1. Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2. Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3. The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-beta1 (TGF-beta1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8-15 P < 0.01) and 5.3-fold reduction (95% CI 1.8-7.7 P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-beta1 and AngII-induced increases in alpha(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4. Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2011
DOI: 10.1161/CIRCIMAGING.111.963587
Abstract: Metabolic and vascular disturbances contribute to diabetic cardiomyopathy, but the role of interstitial fibrosis in early disease is unproven. We sought to assess the relationship between imaging markers of diffuse fibrosis and myocardial dysfunction and to link this to possible causes of early diabetic cardiomyopathy. Hemodynamic and metabolic data were measured in 67 subjects with type 2 diabetes mellitus (age 60±10 years) with no cardiac symptoms. Myocardial function was evaluated with standard echocardiography and myocardial deformation ischemia was excluded by exercise echocardiography. Calibrated integrated backscatter was calculated from parasternal long-axis views. T1 mapping was performed after contrast with a modified Look-Locker technique using saturation recovery images. Amino-terminal propeptides of procollagens type I and III, as well as the carboxy-terminal propeptide of procollagen type I, were assayed to determine collagen turnover. Subjects with abnormal early diastolic tissue velocity (E m ) had shorter postcontrast T1 values ( P =0.042) and higher calibrated integrated backscatter ( P =0.007). They were heavier ( P =0.003) and had worse exercise capacity ( P .001), lower insulin sensitivity ( P =0.003), and blunted systolic tissue velocity ( P =0.05). Postcontrast T1 was associated with diastolic dysfunction (E m r =0.28, P =0.020 E/E m r =−0.24, P =0.049), impaired exercise capacity ( r =0.30, P =0.016), central adiposity ( r =−0.26, P =0.046), blood pressure (systolic r =−0.30, P =0.012 diastolic r =−0.49, P .001), and insulin sensitivity ( r =0.30, P =0.037). The association of T1 with E/E m (β=−0.31, P =0.017) was independent of blood pressure and metabolic disturbance. Amino-terminal propeptide of procollagens type III was linked to diastolic dysfunction (E m r =−0.32, P =0.008) and calibrated integrated backscatter ( r =0.30, P =0.015) but not T1 values. The association between myocardial diastolic dysfunction, postcontrast T1 values, and metabolic disturbance supports that diffuse myocardial fibrosis is an underlying contributor to early diabetic cardiomyopathy.
Publisher: Wiley
Date: 06-2018
DOI: 10.1111/IMJ.13820
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/IMJ.13380
Abstract: Many patients with cirrhosis follow complex medication and dietary regimens, and those with decompensated cirrhosis suffer debilitating complications. These factors impact activities of daily living and quality of life. To explore the concerns and challenges of people with cirrhosis and their use of support services and to also describe health professionals' (HP) perspectives of patients' concerns. This is a cross-sectional study at a tertiary liver clinic involving 50 patients and 54 HP. Data were collected using structured questionnaires. The study includes patients' report of their challenges roblems now that they have cirrhosis ('patient-volunteered concerns') and HP' report of patients' concerns. Both also ranked a list of 10 potential concerns. Patients were, on average, 58 years old (SD = 10.2), mostly male (78%), Caucasian (86%) and with compensated cirrhosis (60%). The patients' most common volunteered concerns related to managing symptoms, emotional issues and disease. Most ranked 'developing liver cancer' (79%), 'losing ability to do daily tasks for yourself' (76%), 'fear of dying' (64%) and 'fear of the unknown' (64%) as priority concerns. Regarding the use of support services, 24% of patients had accessed a dietician, 20% a pharmacist and 18% a psychologist. From the HP' perspective, the patients' most significant challenges related to managing disease (65%) and symptoms (48%), access to healthcare (56%) and information/knowledge (48%). Our findings demonstrate that cirrhosis (its symptoms, complications and treatment) is associated with significant concerns for patients. The discrepancies between the views of HP and patients suggest that we may not be measuring or addressing patients' needs appropriately.
Publisher: Wiley
Date: 19-08-2019
DOI: 10.1111/BCP.14033
Publisher: Wiley
Date: 14-06-2020
DOI: 10.1111/BCP.14390
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/IMJ.13022
Publisher: Wiley
Date: 04-2012
Publisher: Elsevier BV
Date: 03-2017
Publisher: CSIRO Publishing
Date: 2018
DOI: 10.1071/PY17127
Abstract: 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.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2018
Publisher: American Medical Association (AMA)
Date: 05-2015
DOI: 10.1001/JAMAINTERNMED.2015.0324
Abstract: 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 in idual 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.
Publisher: Springer Science and Business Media LLC
Date: 10-2016
DOI: 10.1007/S00038-015-0739-Y
Abstract: 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 < 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 %). 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.
Publisher: Wiley
Date: 04-2011
DOI: 10.1111/J.1445-5994.2011.02439.X
Abstract: Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.
Publisher: Wiley
Date: 13-01-2022
DOI: 10.1002/PRP2.911
Abstract: Infection of humans with SARS‐CoV‐2 virus causes a disease known colloquially as “COVID‐19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE‐2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.” Longitudinal clinical studies in a group of subjects who were infected with SARS‐CoV‐2 have been compared to a non‐infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self‐report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid‐derived 2‐like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re‐purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.
Publisher: Ubiquity Press, Ltd.
Date: 2020
DOI: 10.5334/IJIC.5456
Publisher: Wiley
Date: 11-2016
DOI: 10.1111/IMJ.13250
Publisher: Elsevier BV
Date: 05-2019
Publisher: AMPCo
Date: 03-2012
DOI: 10.5694/MJA11.11251
Abstract: Many have asked "what is the benefit of the DHP over the current situation?" We believe that the responsiveness of research to community health needs and the balance of research and teaching outcomes in academic institutions can be improved, and stronger incentives to integrate research outcomes into clinical practice can be provided. The DHP is thus set up differently to a clinical research centre. The aim of our DHP is to improve health outcomes by means of coordinated excellence in teaching, research and clinical care. Technical efficiencies and excellence in care mean that financial efficiencies will occur. Joint clinical, research and teaching initiatives are underway, and plans are being developed to teach future clinical staff the science of clinician-directed, rational use of medical resources. These include pathology, imaging services, pharmaceuticals and patient referrals, assisted by published expert guidelines. There are significant administrative and personnel issues to surmount, but planning for integration has begun, and plans for turning research outcomes into clinical care plans are already emerging.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-07-2019
DOI: 10.1002/HEP4.1398
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Publisher: Wiley
Date: 10-07-2019
DOI: 10.1111/BCP.14028
Publisher: American Physiological Society
Date: 11-2007
DOI: 10.1152/AJPHEART.01167.2006
Abstract: Diastolic dysfunction is an increasingly recognized complication of diabetes that develops in relatively young patients as a result of diabetic cardiomyopathy (DCM). With recent advances in echocardiographic technology now permitting the reliable assessment of diastolic function in the rat, we examined cardiac function and structure in diabetic rodents and assessed the effects of intervening with tranilast, an antifibrotic compound that has been shown to attenuate the actions of transforming growth factor-β (TGF-β) in cardiac fibroblasts. We also sought to examine the mechanism whereby tranilast inhibits the actions of TGF-β. Six-week-old heterozygous (mRen-2)27 rats were randomized to receive either streptozotocin or citrate buffer and then further randomized to receive either tranilast (400 mg·kg −1 ·day −1 by twice daily gavage) or vehicle for another 8 wk. Cell signaling was examined in neonatal cardiac fibroblasts. After 8 wk, diabetic rats showed evidence of impaired diastolic function with reduced early-to-late atrial wave ratio and prolonged deceleration time in association with fibrosis, apoptosis, and hypertrophy (all P 0.05). Treatment with tranilast prevented the development of diastolic dysfunction and the histopathological features of DCM. While tranilast did not affect Smad phosphorylation, it significantly attenuated TGF-β-induced p44/42 mitogen-activated protein kinase phosphorylation.
Publisher: BMJ
Date: 03-2015
Publisher: Wiley
Date: 02-2022
DOI: 10.1002/PRP2.918
Publisher: Wiley
Date: 02-2022
DOI: 10.1002/PRP2.917
Abstract: SARS‐CoV‐2 interacting with its receptor, angiotensin‐converting enzyme 2 (ACE2), turns the host response to viral infection into a dysregulated uncontrolled inflammatory response. This is because ACE2 limits the production of the peptide angiotensin II (Ang II) and SARS‐CoV‐2, through the destruction of ACE2, allows the uncontrolled production of Ang II. Recovery from trauma requires activation of both a tissue response to injury and activation of a whole‐body response to maintain tissue perfusion. Tissue and circulating renin‐angiotensin systems (RASs) play an essential role in the host response to infection and injury because of the actions of Ang II, mediated via its AT 1 receptor. Both tissue and circulating arms of the renin angiotensin aldosterone system's (RAAS) response to injury need to be regulated. The effects of Ang II and the steroid hormone, aldosterone, on fluid and electrolyte homeostasis and on the circulation are controlled by elaborate feedback networks that respond to alterations in the composition and volume of fluids within the circulatory system. The role of Ang II in the tissue response to injury is however, controlled mainly by its metabolism and conversion to Ang‐(1‐7) by the enzyme ACE2. Ang‐(1‐7) has effects that are contrary to Ang II‐AT 1 R mediated effects. Thus, destruction of ACE2 by SARS‐CoV‐2 results in loss of control of the pro‐inflammatory actions of Ang II and tissue destruction. Therefore, it is the response of the host to SARS‐CoV‐2 that is responsible for the pathogenesis of COVID‐19.
Publisher: Bentham Science Publishers Ltd.
Date: 11-12-2017
Publisher: Informa UK Limited
Date: 20-11-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2019
Publisher: Wiley
Date: 20-06-2019
DOI: 10.1111/BCP.13979
Publisher: Springer Science and Business Media LLC
Date: 21-02-2018
DOI: 10.1007/S40262-018-0633-X
Abstract: In the original publication, Page 3, Sect. 4.3, the first sentence was incorrectly published.
Publisher: Springer Science and Business Media LLC
Date: 30-05-2015
DOI: 10.1007/S11060-015-1816-Z
Abstract: 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 erting 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.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2021
Publisher: Wiley
Date: 06-04-2017
DOI: 10.1111/BCP.13281
Publisher: Springer Science and Business Media LLC
Date: 13-09-2016
Publisher: Wiley
Date: 12-04-2021
DOI: 10.5694/MJA2.51025
Publisher: Frontiers Media SA
Date: 07-08-2017
Publisher: Wiley
Date: 23-05-2019
DOI: 10.1111/BCP.13963
Publisher: AMPCo
Date: 06-05-2020
DOI: 10.5694/MJA2.50603
Publisher: Oxford University Press (OUP)
Date: 27-07-2019
DOI: 10.1093/JAT/BKY043
Abstract: 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 s le 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.
Publisher: Wiley
Date: 05-04-2012
Publisher: Wiley
Date: 22-08-2018
DOI: 10.1111/BCP.13724
Publisher: Wiley
Date: 09-2014
DOI: 10.5694/MJA13.11020
Publisher: REPO4EU
Date: 12-09-2023
DOI: 10.58647/REXPO.23002
Publisher: Informa UK Limited
Date: 16-08-2022
Publisher: Informa UK Limited
Date: 19-06-2013
DOI: 10.3109/09553002.2013.800248
Abstract: 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. Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with (60)Co γ-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. 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 (t(HRSmax) and t(IRRmax)) were independent of dose-rate. The t(HRSmax) and t(IRRmax) 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 t(HRSmax) may correspond to exposure time during which NHEJ is deficient while t(IRRmax) may correspond to exposure time during which NHEJ is complete. HRS response may be maximal if exposure times are shorter than t(HRSmax) irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.
Publisher: Future Medicine Ltd
Date: 11-2012
DOI: 10.2217/PGS.12.140
Publisher: Wiley
Date: 05-2021
DOI: 10.1002/PRP2.772
Publisher: Wiley
Date: 03-03-2020
DOI: 10.1111/BCP.14242
Publisher: Wiley
Date: 12-04-2020
DOI: 10.1002/PDS.4999
Publisher: Wiley
Date: 08-12-2011
Publisher: CSIRO Publishing
Date: 2014
DOI: 10.1071/AH14083
Abstract: Objective To implement and evaluate strategies for improving access to emergency department (ED) care in a tertiary hospital. Methods A retrospective pre–post intervention study using routinely collected data involving all patients presenting acutely to the ED of a major tertiary hospital over a 2-year period. Main outcome measures were changes in: the percentage of patients exiting the ED (all patients, patients discharged directly from the ED, patients admitted to inpatient wards) mean patient transit times in the ED inpatient mortality rates rates of ED ‘did not wait’ and re-presentations within 48 h of ED discharge and selected safety indicators. Qualitative data on staff perceptions of interventions were also gathered. Results Working groups focused on ED internal processes, ED–inpatient unit interface, hospital-wide discharge processes and performance monitoring and feedback. Twenty-five different reforms were enacted over a 9-month period from April to December 2012. Comparing the baseline period (January–March 2012) with the post-reform period (January–March 2013), the percentage of patients exiting the ED within 4 h rose for all patients presenting to the ED (from 32% to 62%), for patients discharged directly from the ED (from 41% to 75%) and for admitted patients (from 12% to 32% P 0.001 for all comparisons). The mean (±s.d.) time all patients spent in the ED was reduced from 7.2 ± 5.8 to 4.4 ± 3.5 h (P 0.001) and, for admitted patients, was associated with reduced in-hospital mortality (from 2.3% to 1.7% P = 0.045). The ‘did not wait’ rates in ED fell from 6.9% to 1.9% (P 0.001), whereas ED re-presentations within 48 h among patients discharged from the ED rose slightly (from 3.1% to 3.8% P = 0.023). Improvements in outcome measures were maintained over the subsequent 12 months. Conclusions Multiple reforms targeting processes both within the ED and its interface with inpatient units greatly improved access to ED care over 12 months and were associated with decreased in-hospital mortality. What is known about this topic? Prolonged stays in the ED result in overcrowding, delayed ambulance access to ED care and increased adverse outcomes for admitted patients. The introduction in Australia of National Emergency Access Targets (NEAT), which stipulate at least 70% of patients in the ED must exit the department within 4 h, have spurred hospitals into implementing a wide range of reforms with varying levels of success in achieving such targets. What does this paper add? This study demonstrates how multiple reforms implemented in a poor performing tertiary hospital caused the proportion of patients exiting the ED within 4 h to double within 9 months to reach levels comparable with best performing peer hospitals. This was associated with a 26% reduction in in-hospital mortality for admitted patients and no clinically significant adverse effects. It demonstrates the importance of robust governance structures, executive sponsorship, cross-disciplinary collaboration, regular feedback of NEAT performance data and major redesign of existing clinical processes, work practices and bed management operations. What are the implications for clinicians and managers? Improving access to emergency care should be regarded as a problem located and resolved both within and without the ED. It requires a whole-of-hospital solution involving interdisciplinary collaboration and significant change in culture and practice relating to inpatient units and their interface with the ED.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Wiley
Date: 07-08-2020
DOI: 10.1111/BCP.14481
Publisher: Wiley
Date: 26-10-2015
DOI: 10.1111/BCP.12741
Publisher: Oxford University Press (OUP)
Date: 02-07-2022
Abstract: For infants exposed in utero to anti-tumour necrosis factor-α [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. 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 s le during the first year of life were included. Overall, 107 infants were enrolled, including 166 blood s les from 71 infliximab-exposed infants and 77 s les 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: xiaozhu.shinyapps.io/antiTNFcalculator2/. 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 s le ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.
Publisher: Wiley
Date: 18-08-2010
DOI: 10.1111/J.1754-9485.2010.02166.X
Abstract: The aim was to compare a private Commonwealth-initiated regional radiation oncology facility in Toowoomba with a Queensland Health facility (QHF) in Brisbane. The comparison concentrated on staffing, case mix and operational budgets, but was not able to look at changes in access to services. Data were collected from the two facilities from January 2008 to June 2008 inclusive. A number of factors were compared, including case mix, staffing levels, delay times for treatment, research, training and treatment costs. The case mix between the two areas was similar with curative treatments making up just over half the work load in both centres and two-thirds the work being made up of cancers of breast and prostate. Staffing levels were leaner in Toowoomba, especially in the areas of nursing, administration and trial coordinators. Research activity was slightly higher in Toowoomba. The average medicare cost per treatment course was similar in both centres ($5000 per course). Total costs of an average treatment including patient, State and Commonwealth costs, showed a 30% difference in costing favouring Toowoomba. This regional radiation oncology centre has provided state-of-the-art cancer care that is close to home for patients living in the Darling Downs region. Both public and private patients have been treated with modest costs to the patient and significant savings to QH. The case mix is similar to the QHF, and there has been significant activity in clinical research. A paperless working environment is one factor that has allowed staffing levels to be reduced. Ongoing support from Governments are required if private facilities are to participate in important ongoing staff training.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2018
DOI: 10.1007/S40262-017-0599-0
Abstract: 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 in idual 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 in idual 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.
Publisher: Wiley
Date: 15-09-2017
DOI: 10.1002/JCPH.937
Abstract: 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 ex le, 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 in idual'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.
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/IMJ.13500
Abstract: 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.
Publisher: Wiley
Date: 26-11-2019
DOI: 10.1002/PRP2.548
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JACC.2010.02.047
Abstract: Myocardial fibrosis is recognized as the pathologic entity of extracellular matrix remodeling. Diffuse, reactive fibrosis is being increasingly recognized in a variety of conditions despite the absence of ischemia. Regardless of the etiology, fibrosis leads to increased myocardial stiffness thereby promoting cardiac dysfunction. This may present clinically with symptoms of cardiac failure although often this is a subclinical disease. Various imaging modalities and collagen biomarkers have been used as surrogate markers to assess the presence, extent, and turnover of myocardial fibrosis. Techniques using echocardiography, cardiac magnetic resonance, and nuclear imaging have been developed to detect early features of systolic and diastolic left ventricular dysfunction and impaired contractile reserve. Further identification of diffuse reactive fibrosis may be possible with evolving cardiac magnetic resonance and molecular techniques. The goal of these approaches is to enable targeted therapy to be instituted earlier, leading to prevention of disease progression and fibrosis accumulation long term.
Publisher: Bentham Science Publishers Ltd.
Date: 02-2005
Abstract: The extracellular matrix (ECM) is a dynamic microenvironment and a major contributor to the adverse ventricular remodelling that follows myocardial infarction (MI), via activation of both direct pro-fibrotic pathways and matrix metalloproteinases (MMPs) that enhance collagenase activity. Reactive fibrosis, i.e. deposition of ECM materials remote from the region of the MI is clearly detrimental to ventricular function and contributory to adverse outcomes post-MI. Therefore, reversal of this process represents an important therapeutic target in post-MI management and treatment of established heart failure. A number of existing agents exert their beneficial effects in part via reductions in ECM deposition. Furthermore, specific anti-fibrotic drugs have been developed and are currently being explored for these and other cardiac conditions where pathological ECM deposition is felt to be contributory to disease progression.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2014
Publisher: Wiley
Date: 10-2022
DOI: 10.1111/IMJ.15922
Abstract: Complementary and alternative medicine (CAM) encompasses a wide range of medication, herbal, dietary and physical therapies that are not usually considered within the realm of conventional therapeutics. Approximately two thirds of the Australian population use CAMs and only around half of this number will discuss their use of these products with their doctor. Clinical use is commonly seen in patients with life‐limiting illness, often because they experience a high burden of symptoms. However, it is also the case that many of these therapies do not have demonstrated efficacy, particularly for the often broad list of conditions and symptoms for which they are chosen to be used. Further, depending on whether they are sold as medications, sold as food supplements or imported illegally and distributed via nonstandard therapeutic channels, several products have had reports of toxicity, severe adverse effects, batch irregularities and drug interactions with other therapies. This awareness, together with lack of standardisation of products and lack of interchangeability between brands has made prescribers unwilling to put patients at risk of harm by supporting their use. In this article, we cover general pharmacological principles around use of a small selection of chemicals used in a medical setting to enable some guidance for use.
Publisher: Springer Science and Business Media LLC
Date: 15-06-2016
DOI: 10.1208/S12248-016-9943-9
Abstract: Model Based Personalised Dosing (MBPD) requires a population pharmacokinetic (PK) or pharmacodynamic model to determine the optimal dose of medication for an in idual. 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 ex le 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.
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/BMJOPEN-2022-063577
Abstract: Postoperative pain is common and frequently addressed through opioid analgesia. This practice must balance the benefits of achieving adequate pain relief against the harms of adverse effects such as opioid-induced ventilatory impairment and opioid use disorder. This student and trainee-led collaborative study aims to investigate and compare the prescription versus consumption of opioids at 7 days postdischarge after common surgical procedures and their impact on patient-reported outcomes regarding postoperative pain. This is a prospective multicentre observational cohort study of surgical patients in Australia, Aotearoa New Zealand and select international sites, conducted by networks of students, trainees and consultants. Consecutive adult patients undergoing common elective and emergency general, orthopaedic, gynaecological and urological surgical procedures are eligible for inclusion, with follow-up 7 days after hospital discharge. The primary outcome will be the proportion of prescribed opioids consumed by patients at 7 days postdischarge. Secondary outcomes will include patient-reported quality of life and satisfaction scores, rate of non-opioid analgesic use, rate of continuing use of opioids at follow-up, rates of opioid prescription from other sources and hospital readmissions at 7 days postdischarge for opioid related side-effects or surgery-related pain. Descriptive and multivariate analyses will be conducted to investigate factors associated with opioid requirements and prescription-consumption discrepancies. OPERAS has been approved in Australia by the Hunter New England Human Research Ethics Committee (Protocol 2021/ETH11508) and by the Southern Health and Disability Ethics Committee (2021 EXP 11199) in Aotearoa New Zealand. Results will be submitted for conference presentation and peer-reviewed publication. Centre-level data will be distributed to participating sites for internal audit. ANZCTR (ID: ACTRN12621001451897p)
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.13184
Publisher: Ubiquity Press, Ltd.
Date: 2020
DOI: 10.5334/IJIC.5641
Publisher: AMPCo
Date: 04-2012
DOI: 10.5694/MJA12.10193
Publisher: Oxford University Press (OUP)
Date: 14-07-2017
DOI: 10.1093/JAT/BKX055
Abstract: 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. S le 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 s les 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.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2020
Publisher: Springer Science and Business Media LLC
Date: 20-07-2017
Publisher: Elsevier BV
Date: 03-2020
Publisher: Wiley
Date: 06-2001
DOI: 10.1046/J.0306-5251.2001.01398.X
Abstract: The aim of this study was to explore whether genetic variation of cytochrome P450 2C9 (CYP2C9) contributes to NSAID-associated gastric ulceration. The hypothesis tested was that CYP2C9 poor metabolizer genotype would predict higher risk of gastric ulceration in patients on NSAIDs that are metabolized by CYP2C9, due to higher plasma NSAID concentrations. Peripheral blood DNA s les from 23 people with a history of gastric ulceration attributed to NSAIDs metabolized by CYP2C9, and from 32 people on NSAIDs without gastropathy, were analysed to determine CYP2C9 genotype. The following genotypes were found: *1/*1 (wild type) in 70% of cases and 58% of controls, *1/*2 in 17% of cases and 29% of controls, *1/*3 in 13% of cases and 13% of controls. The difference between case and control nonwild-type genotype frequency was 11.5% (95% CI -14,37%), with the direction of the difference being against the hypothesis. No in iduals with homozygote poor metaboliser genotype were identified. The differences in genotype frequencies between the two groups were not significant and the frequencies were similar to those in a large published population study. Ninety-five percent binomial confidence interval analysis confirms that there is no apparent clinically significant relationship between CYP2C9 genotype and risk of gastric ulceration although a small difference in risk in poor metabolizers cannot be excluded. These results do not support the hypothesis that gastric ulceration resulting from NSAID usage is linked to the poor metabolizing genotypes of CYP2C9.
Publisher: Wiley
Date: 12-2009
Publisher: Wiley
Date: 08-2017
DOI: 10.1111/IMJ.13505
Abstract: Many patients with chronic disease do not possess the knowledge and skills required to access and interpret appropriate health information. A pilot study in people with liver cirrhosis (n = 50) identified that only 54% of patients could recall being given written information by a clinician and 64% had self-sought information, most commonly using the Internet. Many patients reported difficulties understanding the material and the majority wanted more accessible information. A pilot chronic disease educational booklet was well received by the study participants with 85% reporting it was helpful and 78% using it in between clinic appointments.
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 2011
Publisher: Oxford University Press (OUP)
Date: 15-02-2005
DOI: 10.1016/J.CARDIORES.2004.10.041
Abstract: The pathological accumulation of extracellular matrix is a characteristic feature of diabetic cardiomyopathy that is directly related to a loss of function. Tranilast (n-[3,4-anthranilic acid), used for the treatment of fibrotic skin diseases, has also been shown to inhibit transforming growth factor-beta (TGF-beta)-induced matrix production in kidney epithelial cells. To investigate the effects of tranilast in the diabetic heart, we examined its effects in cultured cardiac fibroblasts and then assessed its effects in (mRen-2)27 diabetic rats with established disease (8 weeks after streptozotocin). In vitro studies demonstrated a 58% reduction in TGF-beta1-induced 3[H]-hydroxyproline incorporation with tranilast 30 microM (p<0.01). At 16 weeks, diabetes in the Ren-2 rat was associated with increased cardiac fibrosis and evidence of TGF-beta1 activation, as measured by the abundance of phosphorylated Smad2. Despite persistent hyperglycaemia and hypertension, tranilast attenuated cardiac fibrosis by 37% (p<0.05) in association with reduction in phospho-Smad2 (p<0.01). These findings indicate that tranilast has antifibrotic actions in the Ren-2 model of experimental diabetic cardiac disease by mechanisms that might attributable to reduced TGF-beta activity.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2012
Publisher: Wiley
Date: 07-2011
DOI: 10.1111/J.1445-5994.2009.02160.X
Abstract: Accurate knowledge of the glomerular filtration rate (GFR) is imperative in the intensive care unit (ICU) as renal status is important for medical decisions, including drug dosing. Recently, an estimation of GFR (eGFR) was suggested as a method of estimating GFR. How well this formula predicts GFR in unwell patients with normal initial serum creatinine concentrations has not been examined. The accuracy of the eGFR (before and after adjustment for actual body surface area (BSA)) was compared with measured and with estimated creatinine clearance using the Cockcroft Gault (CG) formula adjusted for total and lean body weight. A total of 237 observations was recorded in 47 subjects. These were initially analysed independently, and then using the first observation only. Overall the mean difference between measured creatinine clearance and eGFR was -12 mL/min (95% confidence interval (CI) -20 to -3), between measured creatinine clearance and CG +17 mL/min (95% CI 9-24), between measured creatinine clearance and CG adjusted for ideal body weight +12 mL/min (95% CI 4-21) and between measured creatinine clearance and eGFR 'unadjusted' for BSA 5 mL/min (95% CI -2-13). Using either eGFR or CG formulae to estimate renal function in ICU subjects with normal serum creatinine concentrations is inaccurate. Although correcting for BSA improves the eGFR, this requirement to measure height and weight removes a major attraction for its use. We suggest that eGFR should not be automatically calculated in the ICU setting.
Publisher: Croatian Society for Medical Biochemistry and Laboratory Medicine
Date: 2013
DOI: 10.11613/BM.2013.035
Publisher: Wiley
Date: 09-2018
DOI: 10.1111/IMJ.14020
Publisher: CSIRO Publishing
Date: 08-04-2021
DOI: 10.1071/CH20380
Abstract: Although cannabis has been used for several thousand years, the exact composition of the cannabinoids patients are administered for different symptoms has remained largely unknown. While this absence of catalogued information may be accepted in some cultures, the use of cannabis as a human product in the registered medicines setting requires knowing its composition so that doses can be standardised between patients. This is particularly so in clinical trials that are currently under way to determine the efficacy of a product. Although the major cannabinoids of interest to prescribers are well known – tetrahydrocannabinol and cannabidiol and the corresponding acids tetrahydrocannabinolic acid and cannabidiolic acid, the cannabis plant contains many more phytocannabinoids. We have developed and validated a robust and fast (11 min) isocratic HPLC method for the analysis of 17 phytocannabinoids. The method had an analytical range of 1–150 μg mL−1 for tetrahydrocannabinolic acid and cannabidiolic acid, 0.5–75 μg mL−1 for tetrahydrocannabinol and cannabidiol, and 0.5–20 μg mL−1 for the remaining 13 cannabinoids. The method had excellent repeatability with a relative standard deviation of between 5 and 14 % and a bias of between –8.6 and 6 % for the 17 cannabinoids. The method was applied to the analysis of medicinal cannabis products, including both flos and oils with results matching the supplier’s certificate of analysis. This simple fast isocratic method with basic HPLC equipment can be easily transferred to any analytical laboratory interested in the identification and quantitation of cannabinoids.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2016
DOI: 10.1007/S00280-016-3071-1
Abstract: Therapeutic drug monitoring (TDM) is being considered as a tool to in idualise 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. 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. 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). 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-05-2022
DOI: 10.1002/HEP4.1999
Publisher: Therapeutic Guidelines Limited
Date: 02-2021
Publisher: AMPCo
Date: 06-2016
DOI: 10.5694/MJA16.00234
Publisher: Cambridge University Press (CUP)
Date: 03-06-2022
Publisher: Informa UK Limited
Date: 09-07-2019
Publisher: Wiley
Date: 08-2020
DOI: 10.1111/IMJ.14948
Publisher: Springer Science and Business Media LLC
Date: 02-05-2016
DOI: 10.1007/S11764-016-0545-4
Abstract: 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. 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. 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2016
DOI: 10.1007/S40262-015-0363-2
Abstract: 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.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jennifer Martin.