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"Bolton, Damien"
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68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review
by
Lawrentschuk, Nathan
,
Corfield, Julia
,
Bolton, Damien
in
Antigens
,
Medical imaging
,
Positron emission tomography
2018
PurposeTo systematically review currently available data on 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) used for the primary staging of high-risk prostate cancer.MethodsWe performed critical reviews of EMBASE, Web of Science (including MEDLINE) and Cochrane databases in October 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. We included studies that utilized 68Ga-PSMA PET for primary staging of prostate cancer. Quality was assessed using the Critical Appraisal Skills Programme checklist for diagnostic test studies.ResultsFollowing our systematic search strategy, 12 studies were included for assessment. These studies comprised a total of 322 patients who underwent 68Ga-PSMA PET scanning for the purpose of primary staging. Only 5 of these studies included histopathologic correlation data. High variation in methodology and outcomes such as sensitivity (range 33–99%) and specificity (> 90%) was seen across all studies. The ability of 68Ga-PSMA PET to detect malignant lesions was evident across studies, with most studies demonstrating increased detection rates with respect to conventional imaging modalities.ConclusionsIn the primary staging of prostate cancer 68Ga-PSMA PET appears to outperform traditional imaging modalities. Overall, there are few high-quality studies investigating 68Ga-PSMA PET in this sub-group highlighting the need for formal assessment of PSMA PET in the form of large-volume, prospective studies.
Journal Article
Social determinants of health: does socioeconomic status affect access to staging imaging for men with prostate cancer
by
Perera, Marlon
,
Bolton, Damien M
,
Kelly, Brian D
in
Biopsy
,
Diagnostic tests
,
Geographical distribution
2023
Socioeconomic status (SES), race and geographical factors are known to impact prostate cancer management and outcomes. We aimed to assess these factors with regard to access to novel imaging in prostate cancer. Using the Prostate Cancer Outcomes Registry of Victoria (PCOR-Vic) we identified 5256 men diagnosed with prostate cancer via biopsy. Following the introduction of government rebate, the access to MRI improved with respect to SES. Access to PET imaging remains poor with respect to SES and geographical location in the absence of Federal funding. Further improvements for men with low SES and regional areas to access PET staging.
Journal Article
Fluoroquinolone resistance in urinary tract infections: Epidemiology, mechanisms of action and management strategies
2024
Background
Fluoroquinolone resistance is an issue of concern amongst physicians worldwide. In urology, fluoroquinolones are often used in the treatment of acute pyelonephritis and prostatitis, as well as infections caused by multidrug‐resistant pathogens.
Aims
We aim to highlight the importance of antimicrobial stewardship and the need for ongoing biomedical research to discover novel agents in our losing battle against resistant pathogens.
Materials and methods
In this review, we survey the literature and summarise fluoroquinolone resistance as it pertains to pyelonephritis and prostatitis, as well as alternative treatment strategies and prevention of multidrug resistance.
Results
The rise of fluoroquinolone resistance in bacteria has reduced the available treatment options, often necessitating hospital admission for intravenous antibiotics, which places an additional burden on both patients and the healthcare system. Many countries such as Australia have attempted to limit fluoroquinolone resistance by imposing strict prescribing criteria, though these efforts have not been entirely successful. Solutions to overcome resistance include prevention, combination therapy and the development of novel antimicrobial agents.
Conclusions
Prevention of the proliferation of resistant organisms by antimicrobial stewardship is paramount, and urologists are obliged to be aware of responsible prescribing practices such as referring to local guidelines when prescribing. By reserving fluoroquinolones for infections in which they are truly indicated and by prescribing based on both patient and local environmental factors, we can preserve this effective resource for future use.
Journal Article
Machine learning to support social media empowered patients in cancer care and cancer treatment decisions
2018
A primary variant of social media, online support groups (OSG) extend beyond the standard definition to incorporate a dimension of advice, support and guidance for patients. OSG are complementary, yet significant adjunct to patient journeys. Machine learning and natural language processing techniques can be applied to these large volumes of unstructured text discussions accumulated in OSG for intelligent extraction of patient-reported demographics, behaviours, decisions, treatment, side effects and expressions of emotions. New insights from the fusion and synthesis of such diverse patient-reported information, as expressed throughout the patient journey from diagnosis to treatment and recovery, can contribute towards informed decision-making on personalized healthcare delivery and the development of healthcare policy guidelines.
We have designed and developed an artificial intelligence based analytics framework using machine learning and natural language processing techniques for intelligent analysis and automated aggregation of patient information and interaction trajectories in online support groups. Alongside the social interactions aspect, patient behaviours, decisions, demographics, clinical factors, emotions, as subsequently expressed over time, are extracted and analysed. More specifically, we utilised this platform to investigate the impact of online social influences on the intimate decision scenario of selecting a treatment type, recovery after treatment, side effects and emotions expressed over time, using prostate cancer as a model. Results manifest the three major decision-making behaviours among patients, Paternalistic group, Autonomous group and Shared group. Furthermore, each group demonstrated diverse behaviours in post-decision discussions on clinical outcomes, advice and expressions of emotion during the twelve months following treatment. Over time, the transition of patients from information and emotional support seeking behaviours to providers of information and emotional support to other patients was also observed.
Findings from this study are a rigorous indication of the expectations of social media empowered patients, their potential for individualised decision-making, clinical and emotional needs. The increasing popularity of OSG further confirms that it is timely for clinicians to consider patient voices as expressed in OSG. We have successfully demonstrated that the proposed platform can be utilised to investigate, analyse and derive actionable insights from patient-reported information on prostate cancer, in support of patient focused healthcare delivery. The platform can be extended and applied just as effectively to any other medical condition.
Journal Article
Seminal papers in urology: maintenance Bacillus Calmette-Guerin (BCG) immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized southwest oncology group study (SWOG-8507)
by
Bolton, Damien
,
O’Callaghan, Michael
,
Tempo, Jake
in
Bacillus Calmette-Guerin vaccine
,
Bias
,
Bladder Cancer
2023
The South West Oncology Group’s 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear.
Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy.
Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35–49) RFS at five years in the control arm and 60% RFS (53–67 95% CI) in the maintenance arm (
p
< 0.0001). Only 16% of patients in the treatment arm received all of the scheduled maintenance courses of BCG.
The study’s seminal results correlate with contemporary systematic review and have guided international guidelines.
Journal Article
Contemporary status of diagnostic endoluminal ultrasound and optical coherence tomography in the ureter
2024
Objective
To evaluate via a review of published literature, the efficacy of endoluminal ultrasound (ELUS) and optical coherence tomography (OCT) in the following ureteric diseases: urolithiasis, upper tract urothelial carcinoma, stricture disease and pelvic‐ureteric junction obstruction (PUJO).
Patients and methods
Ureteric high‐frequency ELUS provides 360° imaging, to a depth of 20 mm, and has been demonstrated to assess ureteric stricture length, degree of fibrosis and aetiology. OCT produces high‐quality images with a penetration depth of 2 mm. ELUS has proven to be useful at the time of endopyelotomy for PUJO as it can identify crossing vessels, some not detectable on CT angiography, allowing the urologist to avoid these when making their incision. Ureteric ELUS may be utilised for submucosal ureteric stones as they are highly visible. Endoluminal ultrasound may be deployed in the case of known sub‐mucosal urolithiasis when the ureter appears stone‐free. It may help identify sub‐mucosal stones or stones within diverticulum.
Results
Endoluminal ultrasound has been analysed for its use in determining muscle‐invasive urothelial carcinoma of the ureter. The PPV for ≥pT2 was only 16.7% in one study of six patients with MIBC and 76.2% in 21 patients with
Journal Article
Targeting HIF-1α to Prevent Renal Ischemia-Reperfusion Injury: Does It Work?
2018
Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.
Journal Article
Erectile dysfunction: a global review of intracavernosal injectables
by
Teh, Jiasian
,
Duncan, Catriona
,
Lawrentschuk, Nathan
in
Anxiety
,
Clinical medicine
,
Erectile dysfunction
2019
PurposeData assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice.MethodsA systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents.ResultsICIs demonstrate clinical efficacy in 54–100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3–6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved.ConclusionsICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.
Journal Article
Can online support groups address psychological morbidity of cancer patients? An artificial intelligence based investigation of prostate cancer trajectories
2020
Online Cancer Support Groups (OCSG) are becoming an increasingly vital source of information, experiences and empowerment for patients with cancer. Despite significant contributions to physical, psychological and emotional wellbeing of patients, OCSG are yet to be formally recognised and used in multidisciplinary cancer support programs. This study highlights the opportunity of using Artificial Intelligence (AI) in OCSG to address psychological morbidity, with supporting empirical evidence from prostate cancer (PCa) patients.
A validated framework of AI techniques and Natural Language Processing (NLP) methods, was used to investigate PCa patient activities based on conversations in ten international OCSG (18,496 patients- 277,805 conversations). The specific focus was on activities that indicate psychological morbidity; the reasons for joining OCSG, deep emotions and the variation from joining through to milestones in the cancer trajectory. Comparative analyses were conducted using t-tests, One-way ANOVA and Tukey-Kramer post-hoc analysis.
PCa patients joined OCSG at four key phases of psychological distress; diagnosis, treatment, side-effects, and recurrence, the majority group was 'treatment' (61.72%). The four groups varied in expression of the intense emotional burden of cancer. The 'side-effects' group expressed increased negative emotions during the first month compared to other groups (p<0.01). A comparison of pre-treatment vs post-treatment emotions showed that joining pre-treatment had significantly lower negative emotions after 12-months compared to post-treatment (p<0.05). Long-term deep emotion analysis reveals that all groups except 'recurrence' improved in emotional wellbeing.
This is the first empirical study of psychological morbidity and deep emotions expressed by men with a new diagnosis of cancer, using AI. PCa patients joining pre-treatment had improved emotions, and long-term participation in OCSG led to an increase in emotional wellbeing, indicating a decrease in psychological distress. It is opportune to further investigate AI in OCSG for early psychological intervention as an adjunct to conventional intervention programs.
Journal Article
Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent
by
Chang, Mike
,
Shulkes, Arthur
,
Patel, Oneel
in
Acute Kidney Injury - drug therapy
,
Acute Kidney Injury - physiopathology
,
Animals
2017
Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn2+ against renal IRI is unclear. Although Co2+ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of HIF1α, HIF2α and HIF3α has not been investigated previously.
The efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn2+ treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot.
Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn2+ induced expression of HIF1α and HIF2α but not HIF3α in HK-2 and ACHN cells.
ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications.
Journal Article
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