Rural Clinical School - Research Publications
Now showing items 1-12 of 243
Real-World Data on Outcomes in Metastatic Castrate-Resistant Prostate Cancer Patients Treated With Abiraterone or Enzalutamide: A Regional Experience
(FRONTIERS MEDIA SA, 2021-06-18)
Background: Both abiraterone and enzalutamide have shown to improve overall survival (OS), progression-free survival (PFS) and prostate-specific antigen (PSA) response in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of previous treatment with chemotherapy (COU-AA3011, COU-AA3022, AFFIRM3 and PREVAIL4). The data regarding the impact of these treatments in the real world setting is scarce. This study assessed the real world survival and disease outcomes in mCRPC patients in a regional health service in Victoria with the use of abiraterone and enzalutamide. Methods: This retrospective clinical audit included 75 patients with diagnosis of mCRPC treated with either abiraterone or enzalutamide between January 1, 2014, and December 31, 2019, at Goulburn Valley Health. Patients were stratified according to the drug received, Eastern Cooperative Oncology Group (ECOG) performance status, Gleason score, burden of disease at diagnosis, presence of visceral metastases and use of previous chemotherapy. The primary end point was PSA response (defined as a reduction in the PSA level from baseline by 50% or more). The secondary outcomes were PSA PFS, radiographic PFS, and OS. Results: Thirty-seven patients received enzalutamide, and the other 38 received abiraterone. Only 20% of patients in either group had visceral metastases. 32% of patients receiving enzalutamide had a high burden of disease, compared to 53% receiving abiraterone. 38% of patients in the enzalutamide group and 53% in the abiraterone group had received prior chemotherapy. PSA response rates were higher in the enzalutamide group than abiraterone group (70.3% vs 37.8%). Both PSA and radiographic PFS were longer in the enzalutamide group than abiraterone group; 7 months vs 5 months for both end points. OS was also found to be longer in patients receiving enzalutamide; 30 months compared to only 13 months in patients receiving abiraterone. Conclusion: Both abiraterone and enzalutamide have shown to result in significant PSA response rates, as well as PFS and OS benefit in mCRPC patients in the real world setting. The difference in responses and survival benefit are probably impacted by the unbalanced burden of disease.
Genetic risk for dengue hemorrhagic fever and dengue fever in multiple ancestries.
(Elsevier BV, 2020-01)
BACKGROUND: Genetic risk factors for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and dengue fever (DF) are limited, in particular there are sparse data on genetic risk across diverse populations. METHODS: We conducted a genome-wide association study (GWAS) in a derivation and validation sample of 7, 460 participants of Latin American, South Asian, and South East Asian ancestries. We then developed a weighted polygenic risk score (PRS) for each participant in each of the validation cohorts of the three ancestries to predict the risk of DHF/DSS compared to DF, DHF/DSS compared to controls, and, DF compared to controls. FINDINGS: The risk of DHF/DSS was significantly increased, odds ratio [OR] 1.84 (95%CI 1.47 to 2.31) (195 SNPs), compared to DF, fourth PRS quartile versus first quartile, in the validation cohort. The risk of DHF/DSS compared to controls was increased (OR=3.94; 95% CI 2.84 to 5.45) (278 SNPs), as was the risk of DF compared to controls (OR=1.97; 95%CI 1.63 to 2.39) (251 SNPs). Risk increased in a dose-dependent manner with increase in quartiles of PRS across comparisons. Significant associations persisted for PRS built within ancestries and applied to the same or different ancestries as well as for PRS built for one outcome (DHF/DSS or DF) and applied to the other. INTERPRETATION: There is a strong genetic effect that predisposes to risk of DHF/DSS and DF. The genetic risk for DHF/DSS is higher than that for DF when compared to controls, and this effect persists across multiple ancestries.
Experience of Healthcare Access in Australia during the First Year of the COVID-19 Pandemic
Changes in health-seeking behaviours and challenges in accessing care have been reported during the COVID-19 pandemic. This qualitative study examines Australian experiences related to healthcare access during the early months of the pandemic. The study aimed to identify key areas of concern as well as opportunities for services to prevent, manage and treat health concerns when normal access was disrupted. Fifty-nine semi-structured interviews were analysed. Participants were interviewed between August and December in 2020 over telephone or Zoom and were located across Australia. Rapid identification of themes with an audio recordings technique was used to generate themes from the data. Participants described a variety of influences on their health-seeking behaviours, resulting in decisions to delay care or being unable to reach care. Many individuals accessed health services via telehealth and offered a range of perceptions and views on its effectiveness and appropriateness. The findings illustrate that maintenance of health and access to healthcare and psychosocial support were compromised for some individuals, leading to negative impacts on both mental and physical health. This highlights the need to provide mechanisms to facilitate a person's ability to access care in a timely manner during a pandemic.
Home-Based Transabdominal Interferential Electrical Stimulation for Six Months Improves Paediatric Slow Transit Constipation (STC)
BACKGROUND: Transcutaneous electrical stimulation (TES) for one to two months has produced some improvement in treatment-resistant slow-transit constipation (STC) in children. Optimal parameters for treatment are not known. It is possible that more improvement would occur with stimulation for longer. This study examined the effectiveness of stimulation for six months. METHODS: Children with STC confirmed by nuclear transit study (NTS) were enrolled prospectively. All had chronic constipation for greater than two years and had failed medical treatment. TES was performed for one hour/day for six months using the INF 4160 (Fuji Dynamics) portable stimulator and 4 cm × 4 cm electrodes near the belly button and on the back. Families kept bowel diaries and completed PEDSQLCore QOL (4.0) questionnaires before and at end of treatment. RESULTS: Sixty-two children (34 females; seven years, 2-16 year) with STC were studied. Defecation frequency increased in 57/62 (91%, mean ± SEM pre- 1.49 ± 0.20 vs. post- 3.25 ± 0.25 defecation/week, p < 0.0001) with the number with ≥3BA increasing from 6 to 37 (10-59%). Soiling frequency decreased from 4.8 to 1.1 days/week (p <0.001). Abdominal pain decreased from 1.7 to 0.3 days/week (<0.0001), and spontaneous urge to defecate improved. Quality of life (p < 0.01), mean transit index and gastric emptying on NTS improved (p < 0.005). CONCLUSION: Treatment-resistant STC responds to TES using interferential current across the abdomen when given daily for many months. Battery operated stimulators allowed stimulation at home for an hour each day. Stimulation for six months produced clinically significant improvement in defecation frequency, soiling, abdominal pain, urge to defecate, and quality of life in half of these chronic patients.
Undescended testis: What paediatricians need to know
Undescended testis (UDT) occurs when something goes wrong with testicular descent from high in the abdominal cavity to the scrotum. Normal descent occurs in two steps, with the transabdominal phase controlled by a new testicular hormone, insulin-like hormone 3, and the inguinoscrotal phase controlled by androgens. The latter phase requires a complex process of migration from the inguinal abdominal wall to the scrotum and is commonly defective, leading to the high incidence (2-4%) of UDT at birth. The clinical examination of babies and infants aims to confirm the persistence of congenital UDT by 3-6 months, so surgery can be optimally timed at 6-12 months. For those boys who develop acquired UDT later in childhood, the 'ascending' testis often needs surgery between 5 years and 10 years, so all boys should be screened again for UDT at school entry.
Anatomical variations of the renal arterial vasculature: An Australian perspective
INTRODUCTION: Variations of the renal arteries have been studied and published across various population groups, but similar information for the ethnically diverse nation of Australia is lacking. This study describes the pattern of renal artery anomalies in a section of the Australian population based on computed tomography (CT) angiograms of the abdomen and cadaveric dissection. METHODS: The renal arterial vasculature of 594 kidneys from 300 subjects (28 cadavers, 272 CT) was studied. The number and pattern of renal arteries were categorised on the basis of laterality, point of origin and termination in the kidney (superior pole, hilum and inferior pole), symmetry and sex. RESULTS: Multiple renal arteries were discovered in 22% of subjects and 12.12% of kidneys. The most common pattern observed was the presence of one variant renal artery (93.1%), compared to the finding of two (5.6%) and three (1.4%) multiple arteries. The aorta was the most frequent site of origin for anomalous vessels, while the hilum was the predominant point of entry. No significant difference was established between left- and right-sided kidneys (13.8% vs. 12.5%; P = 0.627); however, unilateral distribution was more common than bilateral additional renal arteries (16.7% vs. 3.4%; P < 0.01), and variations among males were more than females (27.2% vs. 15.2%; P < 0.05). A higher rate of multiple renal arteries was noted in cadaveric dissections compared to CT images (46.4% vs. 19.5%; P < 0.01). CONCLUSION: These findings provide application of an evidence-based teaching tool that facilitates education regarding renal arterial variations in Australia.
Quality of referral: What information should be included in a request for diagnostic imaging when a patient is referred to a clinical radiologist?
Referral to a clinical radiologist is the prime means of communication between the referrer and the radiologist. Current Australian and New Zealand government regulations do not prescribe what clinical information should be included in a referral. This work presents a qualitative compilation of clinical radiologist opinion, relevant professional recommendations, governmental regulatory positions and prior work on diagnostic error to synthesise recommendations on what clinical information should be included in a referral. Recommended requirements on what clinical information should be included in a referral to a clinical radiologist are as follows: an unambiguous referral; identity of the patient; identity of the referrer; and sufficient clinical detail to justify performance of the diagnostic imaging examination and to confirm appropriate choice of the examination and modality. Recommended guideline on the content of clinical detail clarifies when the information provided in a referral meets these requirements. High-quality information provided in a referral allows the clinical radiologist to ensure that exposure of patients to medical radiation is justified. It also minimises the incidence of perceptual and interpretational diagnostic error. Recommended requirements and guideline on the clinical detail to be provided in a referral to a clinical radiologist have been formulated for professional debate and adoption.
Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era
AIM: Relapsed/refractory (R/R) aggressive lymphoma outcomes are poor. There is no standard treatment. PACEBOM (prednisolone, doxorubicin, cyclophosphamide, etoposide, bleomycin, vincristine and methotrexate) has shown efficacy for several lymphoma subtypes in published reports. We evaluate PACEBOM+/-rituximab for R/R aggressive lymphomas in this millennium. METHODS: In this retrospective, single-center study, R/R aggressive lymphoma patients who received PACEBOM or its derivatives were identified from the pharmacy database. Demographic, treatment, toxicity and survival data were collected. RESULTS: A total of 37 eligible patients were identified. Histological subtypes included 20 Diffuse Large B-Cell Lymphoma (DLBCL), 10 T-Cell Lymphoma (TCL) and 7 Hodgkin lymphoma. All DLBCL patients had received prior rituximab. Thirty-one (84%) received second-line PACEBOM. Median number of cycles was six (1-6). Eighteen out of 20 B-cell lymphoma patients received R-PACEBOM. Overall response rate was 65%, 70% and 71% in patients with DLBCL, TCL and Hodgkin lymphoma respectively. Thirteen patients underwent autologous stem cell transplant post-PACEBOM. Median follow-up was 49 months (3-201). Most common grade 3-4 toxicities were neutropenia (46%), anemia (24%) and thrombocytopenia (16%). No additional toxicity was seen in patients who received rituximab. CONCLUSION: In this cohort, PACEBOM is active in R/R aggressive lymphoma with manageable toxicity and can be safely combined with rituximab. Outcomes were similar to reports of other salvage regimens. PACEBOM remains a suitable option for R/R aggressive lymphoma, in patients exposed to prior rituximab and those planned for autologous stem cell transplant.
The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study
BACKGROUND: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. RESULTS: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
Retrograde continence enema in children with spina bifida: Not as effective as first thought
AIM: The aim of the study is to investigate the effectiveness of Peristeen retrograde continence enema (RCE) in the management of faecal incontinence in children with spina bifida. METHODS: We identified a homogenous group of spina bifida patients in whom RCE was initiated (Jan 2006-July 2013). Confidential assessments included (i) Fecal Incontinence Quality Of Life (FIQOL), (ii) St Marks Faecal Incontinence score, (iii) Cleveland Clinic Constipation score and (iv) Neurogenic Bowel Dysfunction score. RESULTS: Of 20 patients, 11 (mean age 14.5 ± 5.3 years) were male. Of 20 patients, nine were still using RCE (mean follow-up 4.1 years). Three patients ceased RCE within 10 days, six after 4-12 months and two after 36-48 months. Reasons for cessation included balloon difficulties (n = 4), procedure deemed too difficult (n = 4) and pain (n = 3). There were no differences between the groups in length of training time for technique, instillate fluid/volume used and time taken to perform RCE. There were no differences between the groups for quality of life, faecal incontinence or constipation scores. CONCLUSIONS: We demonstrated a high rate of cessation with RCE in patients with spina bifida. This could not be explained by associated conditions, or by enema-related parameters. One possible explanation is the lack of ongoing outpatient support for the children and their families.