Prince of Wales Clinical School

Prince of Wales, Australia

Prince of Wales Clinical School

Prince of Wales, Australia
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Park S.B.,Prince of Wales Clinical School | Park S.B.,Neuroscience Research Australia | Lin C.S.-Y.,University of New South Wales | Krishnan A.V.,University of New South Wales | And 4 more authors.
Experimental Neurology | Year: 2011

Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na+/K+ pump function. Excitability properties were assessed before and after maximal voluntary contraction (MVC) of the abductor pollicis brevis. Following oxaliplatin infusion, abnormalities developed in the recovery cycle with refractoriness markedly increased. Following activity, changes developed consistent with axonal hyperpolarization, with proportional changes pre- and post-oxaliplatin in normalized threshold. However, recovery cycle parameters following activity were significantly and disproportionally enhanced post-oxaliplatin, with partial normalization of the recovery cycle curve post-activity. Patients with the most abnormal change in the recovery cycle after infusion demonstrated the greatest changes post-contraction. Prominent abnormalities developed in Na+ channel-associated parameters in response to natural activity, without significant alteration in axonal membrane potential or Na+/K+ pump function. Findings from the present series suggest that oxaliplatin affects nerve excitability through voltage-dependent mechanisms, with specific effects mediated through axonal Na+ channel inactivation. © 2010 Elsevier Inc.

Fazalbhoy A.,Prince of Wales Clinical School | Fazalbhoy A.,Neuroscience Research Australia | Birznieks I.,University of Sfax | Birznieks I.,University of Western Sydney | And 4 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

Assessment of spontaneous slow waves in the peripheral blood volume using the photoplethysmogram (PPG) has shown potential clinical value, but the physiological correlates of these fluctuations have not been fully elucidated. This study addressed the contribution of arterial pressure and muscle sympathetic nerve activity (MSNA) in beat-to-beat PPG variability in resting humans under spontaneous breathing conditions. Peripheral PPG waveforms were measured from the fingertip, earlobe, and toe in young and healthy individuals (n = 13), together with the arterial pressure waveform, electrocardiogram, respiration, and direct measurement of MSNA by microneurography. Cross-spectral coherence analysis revealed that among the PPG waveforms, low-frequency fluctuations (0.04-0.15 Hz) in the ear PPG had the highest coherence with arterial pressure (0.71 ± 0.15) and MSNA (0.44 ± 0.18, with a peak of 0.71 ± 0.16 at 0.10 ± 0.03 Hz). The normalized midfrequency powers (0.08-0.15 Hz), with an emphasis on the 0.1-Hz region, were positively correlated between MSNA and the ear PPG (r = 0.77, P = 0.002). Finger and toe PPGs had lower coherence with arterial pressure (0.35 ± 0.10 and 0.30 ± 0.11, respectively) and MSNA (0.33 ± 0.10 and 0.26 ± 0.10, respectively) in the LF band but displayed higher coherence between themselves (0.54 ± 0.09) compared with the ear (P < 0.001), which may suggest the dominance of regional vasomotor activities and a common sympathetic influence in the glabrous skin. These findings highlight the differential mechanisms governing PPG waveform fluctuations across different body sites. Spontaneous PPG variability in the ear includes a major contribution from arterial pressure and MSNA, which may provide a rationale for its clinical utility. © 2012 the American Physiological Society.

Bye W.,Prince of Wales Hospital | Ishaq N.,Prince of Wales Hospital | Bolin T.D.,Prince of Wales Hospital | Duncombe V.M.,Prince of Wales Hospital | Riordan S.M.,Prince of Wales Clinical School
World Journal of Gastroenterology | Year: 2014

Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable. Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years, leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders, including irritable bowel syndrome (IBS). Use of culture-independent molecular techniques already employed to characterise faecal and, to a lesser extent, colonic mucosal microbial populations in IBS, without reliance on insensitive, traditional microbiological culture techniques, has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder, at least that occurring proximally and within reach of sampling. Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

PubMed | University of New South Wales, Prince of Wales Clinical School, Kaiser Permanente, Prince of Wales Hospital and 2 more.
Type: | Journal: European journal of cancer care | Year: 2016

Somatic mutations in key oncogenes in non-small cell lung cancer (NSCLC) and melanoma are important determinants of tumour sensitivity to targeted therapies. Molecular screening for these predictive biomarkers is routinely used to inform treatment decisions; however, little is known about how best to communicate testing and results to patients. This qualitative study aimed to explore advanced cancer patients attitudes and experiences regarding somatic tumour screening to identify their information and support needs. Sixteen NSCLC and eight melanoma patients who had undergone screening participated in a semi-structured face-to-face or telephone interview exploring their understanding, views, preferences and needs regarding screening. Interviews were audiotaped, transcribed and analysed for thematic patterns. Participants expressed positive views and unequivocal acceptance of screening, and understood its role in guiding treatment selection. They preferred to receive information verbally through simple, non-technical language from their oncologist with additional take-home materials. Patients were interested in learning about their test results, but wanted discussion to be focused on practical matters relevant to treatment. While receiving their screening results was not considered burdensome, information overload and cancer-related distress were identified as barriers to test comprehension. Patients may benefit from information and decision-related tools to better understand genomic information and adequately support psychosocial outcomes.

Smith M.A.,University of New South Wales | Liu B.,University of New South Wales | Liu B.,Sax Institute | McIntyre P.,University of Sydney | And 3 more authors.
Journal of Infectious Diseases | Year: 2015

Background.Human papillomavirus (HPV) vaccination targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of females aged 13-26 years continuing to 2009. Whole-population analyses, including effects on the Indigenous population, have not previously been reported. Methods.All hospital admissions between 1999-2011 involving a diagnosis of genital warts were obtained from a comprehensive national database. We compared the age-specific rates before to those after implementation of the vaccination program, according to sex and other characteristics. Results.Admission rates decreased from mid-2007 in females aged 12-17 years (annual decline, 44.1% [95% confidence interval {CI}, 35.4%-51.6%]) and from mid-2008 in females and males aged 18-26 years (annual declines, 31.8% [95% CI, 28.4%-35.2%] and 14.0% [95% CI, 5.1%-22.1%], respectively). The overall reductions from 2006-2007 to 2010-2011 were 89.9% (95% CI, 84.4%-93.4%) for females aged 12-17 years, 72.7% (95% CI, 67.0%-77.5%) for females aged 18-26 years, and 38.3% (95% CI, 27.7%-47.2%) for males aged 18-26 years. Compared with the average annual number before program implementation, about 1000 fewer hospital admissions involved a warts diagnosis during 2010-2011. Reductions after program implementation were similar for Indigenous (86.7% [95% CI, 76.0-92.7]) and non-Indigenous (76.1% [95% CI, 71.6%-79.9%]) females aged 15-24 years (Pheterogeneity =. 08). Conclusions.National population-based hospital data confirm previous clinic-based reports of a marked decline in genital warts diagnoses among young people in Australia after program implementation, including indirect benefits to males. The impact of HPV vaccination appears to be similar in young Indigenous and non-Indigenous females. © 2014 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Taylor M.E.,Falls and Balance Research Group | Lord S.R.,Falls and Balance Research Group | Lord S.R.,University of New South Wales | Delbaere K.,Falls and Balance Research Group | And 4 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2012

Background/Aims: Cognitively impaired older people are at twice the risk of falls compared to cognitively intact, with approximately 60% falling once or more per year. This study aimed to investigate sensorimotor and balance risk factors for falls in cognitively impaired older people. Methods: 177 community-dwelling older people with mild to moderate cognitive impairment (Mini-Mental State Examination < 24, Addenbrooke's Cognitive Examination-Revised < 83) were assessed using the Physiological Profile Assessment (PPA). Falls were recorded prospectively for 12 months using monthly calendars with the assistance of carers. Results: Seventy-one participants (43%) fell ≥2 times in the follow-up period. Impaired simple reaction time, postural sway, leaning balance and increased PPA fall risk score were significantly associated with multiple falls. The area under the receiver-operating characteristic curve for the PPA model including tests of vision, proprioception, knee extension strength, reaction time, postural sway and leaning balance was 0.75 (95% confidence interval: 0.68-0.83). Conclusion: These findings indicate poor performance on physiological fall risk factors, particularly balance, increases the risk of falls in older cognitively impaired people. © 2012 S. Karger AG, Basel.

PubMed | Prince of Wales Clinical School, University of Sydney and University of New South Wales
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

101 Background: Clinical trials have demonstrated the benefits of trastuzumab in treating HER2EBC. However, in routine care it is unclear which patients are recommended treatment, what chemotherapy partners are used and whether patients receive all of their intended treatments. In this study we describe the real world treatment patterns in HER2EBC patients.We undertook a clinical audit of patients diagnosed with HER2EBC (stage I-III) at four Sydney-based cancer centres between 2008 and 2011. We identified patients from pathology records and extracted information on patient and cancer characteristics, treatments planned and received from medical notes and medication charts.203 patients formed the study cohort; median age 55 years (range: 21-91), all but one patient was female. 77 patients had stage I disease, 84 stage II, and 42 stage III. 176 patients (86.7%) were recommended trastuzumab-based treatment and 168 patients initiated therapy. 96 were treated with anthracycline-based chemotherapy and 70 with taxane-based chemotherapy. 76.7% completed the planned number of taxane-based treatments compared with than the 60% receiving anthracycline-based therapies; toxicity being the main reason for not completing treatment. Younger patients (OR 0.89, 95%CI 0.84-0.93, p<0.001) and those with grade 3 tumours compared to grade 1 and 2 combined (OR 3.99, 95%CI 1.31-12.08, p0.014) were more likely to be recommended trastuzumab-based treatment. Younger patients (OR 0.85, 95%CI 0.81-0.90, p <0.001) with a high HER2 gene copy number (OR 4.10, 95%CI 1.06-15.81, p 0.041) multifocal disease (OR 3.53, 95%CI 1.06- 15.82 p 0.023) and stage II and III disease (OR 0.73, 95%CI 0.25-0.90 p 0.011) were more likely to be recommended anthracycline over taxane-based therapy.Trastuzumab-based therapy is standard of care for patients with HER2EBC regardless of patient or cancer characteristics. Whilst chemotherapy partners are determined by patient and cancer characteristics, treatment limiting toxicities also need to be considered in order to maximise patient benefit.

PubMed | Prince of Wales Clinical School, University of Sydney and University of New South Wales
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

100 Background: Pharmaceutical claims are used increasingly to investigate the real-world use and impact of prescribed medicines. Claims databases are established for payment purposes, lack clinical data and only capture prescriptions for which insurers pay a contribution. We compare Pharmaceutical Benefits Scheme (PBS) dispensing claims of HER2EBC patients, with prescriptions written in oncology clinics to determine the accuracy of dispensing data to identify treatment protocols and estimate treatment cycles and durations of therapy.Our cohort comprised 110 female HER2EBC patients commencing treatment at 4 Sydney cancer centres between 2008 and 2011. Patients consented to medical chart audit and linkage to PBS claims. We constructed protocols from prescribing and dispensing records independently, based on the timing of trastuzumab and cytotoxic treatments; estimated the median number of treatment cycles and duration of therapy by protocol; and compared prescription and dispensing data.Patients median age was 53 years (range 21.1-86.2). Based on prescribing data, 67 patients received anthracycline-containing protocols, 43 received taxane only protocols. ACTH and TCH accounted for 90% of all protocols. 75 patients (68.2%) were assigned the same protocols based on prescribing and claims data; 26 did not match as cyclophosphamide falls below the patient copayment for general PBS beneficiaries and is not captured in the claims data. Compared with prescription data, number of treatment cycles was underestimated in dispensing data (ACTH: median 30 vs 44; TCH 26 vs 29); trastuzumab-based treatment is administered weekly in ACTH but only dispensed 3-weekly. Durations of therapy differed by 5% in dispensing versus prescription data (ACTH 422 days vs 466; TCH 368 vs 367).PBS dispensing data is reliable for establishing treatment protocols in concessional beneficiaries and duration of therapy in all patients. Claims data underestimates treatment cycles as administration occurs more frequently than dispensing. These limitations must be considered when undertaking population-based studies using claims data in HER2EBC.

PubMed | Prince of Wales Clinical School, University of New South Wales and St Vincents Hospital
Type: Journal Article | Journal: Interactive cardiovascular and thoracic surgery | Year: 2016

A best evidence topic was written according to a structured protocol. The question addressed was: is cardiac magnetic resonance (CMR) imaging as accurate as echocardiography in the assessment of aortic valve stenosis? Altogether 239 papers were found using the reported search. Only 12 demonstrated the best evidence to answer the clinical question. Nine of these 12 papers found CMR to correlate well with transthoracic echocardiography (TTE) or transoesophageal echocardiography (TOE) in the evaluation of aortic valve stenosis. When aortic valve areas were measured with cardiac tomography (CT) or cardiac catheterization (CC), four papers found CMR to be more accurate than TTE. Eight of 12 papers found CMR to have excellent reliability and reproducibility, as demonstrated by the low inter- and intraobserver variability. Four papers did not estimate intra- or interobserver variability. One paper noted a sensitivity and specificity of 96 and 100%, respectively, when using CMR to detect severe aortic stenosis (AS) that had been diagnosed during CC. A second paper noted a lower sensitivity and specificity of 78 and 89%, respectively, but this was still better than the sensitivities and specificities found when using TOE or TTE to detect severe AS, as noted on CC. We conclude that current evidence finds echocardiography and CMR to be equally reliable in assessing aortic stenosis. CMR has better inter- and intraobserver reliability and demonstrates an advantage over echocardiography in the detection of severe AS with greater specificity and sensitivity. The final choice, however, is as likely to be influenced by the availability of magnetic resonance imaging and expertise in interpreting the results as by accuracy and reliability.

News Article | April 4, 2016

The repair system, similar to the method used by salamanders to regenerate limbs, could be used to repair everything from spinal discs to bone fractures, and has the potential to transform current treatment approaches to regenerative medicine. The UNSW-led research has been published today in the Proceedings of the National Academy of Sciences journal. Study lead author, haematologist and UNSW Associate Professor John Pimanda, said the new technique, which reprograms bone and fat cells into induced multipotent stem cells (iMS), has been successfully demonstrated in mice. "This technique is a significant advance on many of the current unproven stem cell therapies, which have shown little or no objective evidence they contribute directly to new tissue formation," Associate Professor Pimanda said. "We are currently assessing whether adult human fat cells reprogrammed into iMS cells can safely repair damaged tissue in mice, with human trials expected to begin in late 2017." There are different types of stem cells including embryonic stem (ES) cells, which during embryonic development generate every type of cell in the human body, and adult stem cells, which are tissue-specific. There are no adult stem cells that regenerate multiple tissue types. "This technique is ground-breaking because iMS cells regenerate multiple tissue types," Associate Professor Pimanda said. "We have taken bone and fat cells, switched off their memory and converted them into stem cells so they can repair different cell types once they are put back inside the body." The technique developed by UNSW researchers involves extracting adult human fat cells and treating them with the compound 5-Azacytidine (AZA), along with platelet-derived growth factor-AB (PDGF-AB) for approximately two days. The cells are then treated with the growth factor alone for a further two-three weeks. AZA is known to induce cell plasticity, which is crucial for reprogramming cells. The AZA compound relaxes the hard-wiring of the cell, which is expanded by the growth factor, transforming the bone and fat cells into iMS cells. When the stem cells are inserted into the damaged tissue site, they multiply, promoting growth and healing. The new technique is similar to salamander limb regeneration, which is also dependent on the plasticity of differentiated cells, which can repair multiple tissue types, depending on which body part needs replacing. The study's first author, Dr Vashe Chandrakanthan, who developed the technology, said the new technique is an advance on other stem cell therapies being investigated, which have a number of deficiencies. "Embryonic stem cells cannot be used to treat damaged tissues because of their tumour forming capacity. The other problem when generating stem cells is the requirement to use viruses to transform cells into stem cells, which is clinically unacceptable," Dr Chandrakanthan said. "We believe we've overcome these issues with this new technique." Neurosurgeon and Conjoint Lecturer with UNSW's Prince of Wales Clinical School, Dr Ralph Mobbs, will lead the human trials, once the safety and effectiveness of the technique using human cells in mice has been demonstrated. "The therapy has enormous potential for treating back and neck pain, spinal disc injury, joint and muscle degeneration and could also speed up recovery following complex surgeries where bones and joints need to integrate with the body," Dr Mobbs said. Research shows that up to 20% of spinal implants either don't heal or there is delayed healing. The rates are higher for smokers, older people and patients with diseases such diabetes or kidney disease. "Spinal implants currently used to replace damaged or troubled discs don't always weld with the adjacent bones, so by transplanting these reprogrammed stem cells, we hope to be able to better fuse these implants to the host bone," Dr Mobbs said. "This represents a potential huge leap forward for spinal and orthopaedic procedures." Along with confirming that human adult fat cells reprogrammed into iMS stem cells can safely repair damaged tissue in mice, the researchers said further work is required to establish whether iMS cells remain dormant at the sites of transplantation and retain their capacity to proliferate on demand. More information: PDGF-AB and 5-Azacytidine induce conversion of somatic cells into tissue-regenerative multipotent stem cells, PNAS,

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