Achieving equitable access to cancer care and clinical trials in regional Australia: A networked approach to expand capacity and implement COSA teletrials model

Aim: Peoplewith cancer living in regional Victoria are less likely to participate in a clinical trial than metropolitan patients.We established a new geographically based trials network with the gaol of increasing the number of regional cancer patients recruited to clinical trials. Method(s): Initially six regional services and Cancer Trials Australia (CTA) collaborated to form Regional Trials Network Victoria (RTNV). Two more sites, Latrobe Regional Hospital and Mildura Public Hospital were added in 2021. This network represents a population of 1.9 million people and approximately 8000 new cancer diagnoses each year. Access to cancer clinical trials at regional sites was achieved by: Building capacity of regional clinical trial units Improving the efficiency of clinical trial conduct Implementing the COSA teletrial framework Investing in the capability of staff Increasing the number of clinical trials Results: In 2017, the CCV Clinical Trial Management Scheme (CTMS) recorded 1587 Victorians recruited to cancer clinical intervention trials. 428 resided in regional Victoria, but only 81 of these participated at a regional site, with others needing to travel. In 2017, 135 patients were recruited to RTN sites (regional plus Geelong) across 55 trials. By 2021, despite the impacts of the COVID19 pandemic the number of recruiting clinical trials increased by 54% and the number of regional patients recruited to CTMS studies in the network increased to 179. Driven by uptake of teletrials and registry trials total recruitment increased to 620 patients. RTNV leveraged funding to sustain core activity and was awarded $18.5 million from the Medical Research Future Fund to conduct health services research over the next 5 years. Conclusion(s): The RTNV is a successful implementation of a regionally based clinical trials network, improving access and participation of regional patients. Much of the increase was driven by the use of COSA Teletrials methodology.

Cellular miR-6741-5p as a Prognostic Biomarker Predicting Length of Hospital Stay among COVID-19 Patients.

Wide variability exists with host response to SARS-CoV-2 infection among individuals. Circulatory micro RNAs (miRNAs) are being recognized as promising biomarkers for complex traits, including viral pathogenesis. We hypothesized that circulatory miRNAs at 48 h post hospitalization may predict the length of stay (LOS) and prognosis of COVID-19 patients. Plasma miRNA levels were compared between three groups: (i) healthy volunteers (C); (ii) COVID-19 patients treated with remdesivir (an antiviral) plus dexamethasone (a glucocorticoid) (with or without baricitinib, a Janus kinase inhibitor) on the day of hospitalization (I); and COVID-19 patients at 48 h post treatment (T). Results showed that circulatory miR-6741-5p expression levels were significantly different between groups C and I (p < 0.0000001); I and T (p < 0.0000001); and C and T (p = 0.001). Our ANOVA model estimated that all patients with less than 12.42 Log2 CPM had a short LOS, or a good prognosis, whereas all patients with over 12.42 Log2 CPM had a long LOS, or a poor prognosis. In sum, we show that circulatory miR-6741-5p may serve as a prognostic biomarker effectively predicting mortality risk and LOS of hospitalized COVID-19 patients.

Preclinical efficacy and safety of novel SNAT against SARS-CoV-2 using a hamster model.

To address the unprecedented global public health crisis due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we designed and developed a novel antiviral nano-drug, called SNAT (Smart Nano-Enabled Antiviral Therapeutic), comprised of taxoid (Tx)-decorated amino (NH2)-functionalized near-atomic size positively charged silver nanoparticles (Tx-[NH2-AgNPs]) that are stable for over 3 years. Using a hamster model, we tested the preclinical efficacy of inhaled SNAT on the body weight, virus titer, and histopathology of lungs in SARS-CoV-2-infected hamsters, including biocompatibility in human lung epithelium and dermal fibroblasts using lactase dehydrogenase (LDH) and malondialdehyde (MDA) assays. Our results showed SNAT could effectively reverse the body weight loss, reduce the virus load in oral swabs, and improve lung health in hamsters. Furthermore, LDH assay showed SNAT is noncytotoxic, and MDA assay demonstrated SNAT to be an antioxidant, potentially quenching lipid peroxidation, in both the human cells. Overall, these promising pilot preclinical findings suggest SNAT as a novel, safer antiviral drug lead against SARS-CoV-2 infection and may find applications as a platform technology against other respiratory viruses of epidemic and pandemic potential.

COVID-19 Infection Enhances Susceptibility to Oxidative Stress-Induced Parkinsonism.

BACKGROUND: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection. OBJECTIVE: The goal of this study was to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. METHODS: K18-hACE2 mice were infected with SARS-CoV-2 to induce mild-to-moderate disease. After 38 days of recovery, mice were administered a non-lesion-inducing dose of the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS-CoV-2 or MPTP alone. RESULTS: K18-hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS-CoV-2 or MPTP, respectively (P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS-CoV-2 + MPTP group compared with SARS-CoV-2 or MPTP alone. CONCLUSIONS: Our observations have important implications for long-term public health, given the number of people who have survived SARS-CoV-2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS-CoV-2 and are abrogated by vaccination. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Management of acute ureteric colic in a large tertiary centre during the initial COVID-19 pandemic - How did our practice change?

Introduction & Objectives: Treatment of acute ureteric colic according to current BAUS guidelines can be challenging, particularly during the COVID-19 pandemic. We aim to audit our practice during the initial COVID-19 pandemic. Materials & Methods: A retrospective analysis of 94 patients admitted with ureteric colic during the initial COVID-19 pandemic (March to June 2020). Data was collected from records and outcomes compared to a pre-pandemic audit of our acute stone service (January to June 2018). Results: Patient demographics were comparable: 33 admissions/month (pre-COVID 37), average age 52 years (pre-COVID 53 years), and median stone size 6 mm (pre-COVID 5mm). Septic patients (23%, pre-COVID 17%) underwent ureteric stenting (23%, pre-COVID 17%) or nephrostomy (10%, pre-COVID <1%). For non-septic patients, 46% underwent primary treatment (ureteroscopy:ESWL = 1:1, pre-COVID = 2:1), 24% ureteric stenting (pre-COVID 31%) and 30% conservative management (pre-COVID 34%). Median time to primary ureteroscopy (94% successful) and ESWL (76% successful;1-2 sessions) was 24 hours (target <48 hours). Median time from stent insertion to definite ureteroscopy was 5.8 weeks (pre-COVID 6.6 weeks, target <4 weeks) and subsequent cystoscopic stent removal was 4 weeks (target <2 weeks). For patients managed conservatively, median time to outpatient review was 7.1 weeks (pre-COVID 5.4 weeks, target <4 weeks) and follow-up imaging 8.2 weeks. Conclusions: These results from one of the largest stone units in the UK show, that despite the pandemic, primary stone intervention was still achievable within 24 hours. There was a greater reliance on ESWL and nephrostomy insertion due to concerns regarding general anaesthesia and COVID-19.

COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism (preprint)

Background: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection. Objectives: To determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. Methods: hACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP. Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone. Results: hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone. Conclusions: Our observations have important implications for long-term public health, given the number of people that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of PD also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination.

Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene.

The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed the circulating miRNA profile in twelve COVID-19 patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed by real-time polymerase chain reaction (RT-qPCR). Compared with healthy controls, we detected significant changes in the circulating miRNA profile of COVID-19 patients. The miRNAs that were significantly altered in all the COVID-19 patients were miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using miRNA mimics in HEK-293 T cells determined miR-150-5p to have a crucial role in SARS-CoV-2 infection and this was based on the following data: (i) miR-150-5p mimic lowered in vitro SARS-CoV-2 infection; (ii) miR-150-5p inhibitor reversed the effects of miR-150-5p mimic on SARS-CoV-2 infection of cells; and (iii) a novel miRNA recognition element (MRE) was identified in the coding strand of SARS-CoV-2 nsp10, the expression of which could be inhibited by miR-150-5p mimic. Our findings identified crucial miRNA footprints in COVID-19 patients with moderate-severe disease. A combination of co-transfection and Western blotting experiments also determined the ability of miR-150-5p to inhibit SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10. Our investigation showed that a sharp decline in the miR-150-5p plasma levels in COVID-19 patients may support enhanced SARS-CoV-2 infection. Furthermore, this study provides insight into one possible mechanism by which COVID-19-induced changes to miR-150-5p levels may promote SARS-CoV-2 infection via modulating nsp10 expression.

Demonstrating the clinical impact of auditing-update from the Australian Clinical Dosimetry Service

Purpose: The Australian Clinical Dosimetry Service (ACDS) has been auditing Australian and New Zealand radiotherapy providers for nearly 10 years building the National Dataset of audit measurements. The audits have uncovered numerous issues with varying significance. This paper will present an update of the ACDS audits including trends within the National Dataset and recent audit findings and will then cover recent audit of more advanced modalities such as SRS, SBRT, VMAT and adaptive radiotherapy. The presentation will conclude with a summary of the COVID-19 impact on the ACDS. The audits demonstrably improve the treatment quality and safety for patients undergoing radiotherapy. Methods and Materials: The ACDS began life in November 2010 and has developed a comprehensive three level auditing service which has expanded beyond Australia's borders. To minimize dosimetric uncertainties the ACDS has been using Computerized Imaging Reference Systems (CIRS)1 plastic water and phantoms across all on-site audits. As phantom complexity increased to meet auditing needs, CIRS was engaged to produce bespoke phantoms for the ACDS. The most recent examples of this are the Stereotactic Radio-Surgery (SRS) head phantom, SBRT, and a thorax customized for stereotactic ablative radiotherapy (SABR) auditing. Results: Audits provide two key outcomes for participating facilities. The first is that independent measurements demonstrate whether the facility's predicted dose is being delivered to the phantom within an acceptable tolerance. For an out-of-tolerance finding the ACDS works with the facility to resolve any discrepancies on the day of audit. Examples include inaccurate data entry in a planning system or inaccurate phantom positioning. Sometimes, however, there may be a systemic issue with calculation algorithms. The National Dataset has enables the ACDS to identify characteristic behavior of certain equipment combinations. As the ACDS perform more audits, the statistical power of the dataset increases and trends can be identified. This is the second key capability which a mature auditor provides to the auditee. Conclusion: The ACDS has development a coherent and successful auditing service which is proactively responding to changing technologies and environment.

Adult cystic fibrosis diabetes patient education and care needs: have your say - a patient survey

Objectives: Cystic fibrosis-related diabetes (CFRD) impacts approximately 40 to 50% of adults with cystic fibrosis (CF). Effective diabetes education has been shown to improve long-term self-management and quality of life. This survey explores the educational needs of patients with or developing CFRD and sets out to identify the optimal mode of delivery for diabetes education. Methods: Adult pre- and post-transplant patients with CFRD and early glucose metabolism abnormalities from the Royal Prince Alfred Hospital CF Clinic were invited to partake in an online survey via email or text message in December 2020. The study protocol was approved by the Sydney Local Health District Ethics Committee (X20-0434). Results: 46 participants completed the survey with a response rate of 45% (female 54%;CFRD 78%;mean duration since CFRD diagnosis: 13 years;post-transplant 15%). Main sources of diabetes education for participants were the CF Clinic (65%);Google search (30%) and their general practitioner (13%). 72% of participants with CFRD felt they had enough information to manage their diabetes but favoured having a diabetes education resource package. The majority of participants preferred to receive CFRD information via an email package (61%), while others favoured perusing an educational website (37%) or phone app (24%), when requested (44%) or every 6 months (31%). The most common categories of diabetes-related information requested by participants with CFRD were updated diabetic technology (75%), CF diet and food diaries (58%), exercise (56%), management of hyper-(58%) or hypoglycemia (47%) and diabetes and alcohol consumption (42%). Conclusion: Patients with CFRD and early glucose metabolism abnormalities have ongoing educational needs and may require improved resources, preferably via virtual platforms, to supplement in-person care. Future research on the clinical impact of increasing virtual education will be necessary during this COVID-19 pandemic and beyond.

P.1 Deprivation and SARS-CoV-2 in obstetric patients

Introduction: The UK Obstetric Surveillance System (UKOSS) has reported on risk factors for admission to hospital amongst obstetric patients with SARS-CoV-2, however, it did not evaluate deprivation as a risk factor.1 Deprivation is a recognised risk factor for mortality from COVID-19 amongst the general population.2 We, therefore, investigated the demographics, including deprivation scores, of obstetric patients diagnosed with SARS-CoV-2 within our local health board. Methods: Caldicott Guardian approval was obtained and requirement for ethical approval was waived by the local research ethics service. All pregnant or recently pregnant patients (within 6 weeks post-partum) within our health board area with a positive SARS-CoV-2 test between 16 March 2020 and 18 December 2020 were retrospectively identified from regional infection surveillance and local obstetric unit reports. Residential area deprivation was classified using the Scottish Index for Multiple Deprivation (SIMD), with quintile 1 representing the most deprived and quintile 5 representing the least deprived areas. R version 4.0.3 (R Foundation for Statistical Computing) was used to perform analyses. Results: Over the study period, 97 patients tested positive for SARS-CoV-2. Comparison between those in the lowest and highest SIMD quintiles is as shown below. Those from a black or ethnic minority background accounted for 31.9% of positive test results and 50% of admissions to critical care. [Formula presented] Discussion: In this cohort of obstetric patients, mothers from socioeconomically disadvantaged areas accounted for a higher proportion of SARS-CoV-2 positive cases (and hospital / critical care admissions) than those from more affluent areas. This is, to our knowledge, the first study to investigate this association in obstetric patients. The relationship demonstrated between ethnicity, deprivation and SARS-CoV-2 requires further investigation and may have implications for future resource allocation and service planning.

Post-ureteroscopy febrile urinary tract infections are linked to pre-operative stent dwell time: Results from three European endourology centres

Introduction: Indwelling ureteric stents, usually inserted for emergency drainage of an obstructed system, can cause significant morbidity with infections. We aimed to assess pre-operative stent dwell time on infectious complications following ureteroscopy and laser fragmentation (URSL). Material and Methods: Data was retrospectively collected for outcomes of URSL from 3 European endourology centres for patients with pre-operative indwelling ureteric stents. We included data for patient details, stone demographics, operative details, stone free rate (SFR), outcomes and complications between 2011 and 2020. Patients divided into group 1 (<6 months stent dwell time) and group 2 (6 months). Primary outcomes were early post-operative infectious complications (febrile UTI) and ICU access. Analysis with binomial logistic regression (SPSS v.24). Results: 501 patients were included (group 1, n=429;group 2, n=72) [Table 1]. Mean age and operative time in groups 1/2 were 71-30 years and 64-22 years, and 51-28 minutes and 59-31 minutes. Febrile UTI and ICU admissions were seen in 32(8%) and 3(0.7%), and 22(31%) and 1(1.4%) in groups 1/2 respectively. Stent dwell time of 6 months carried significantly higher risk for febrile UTI post URSL (RR=5.45, 95% CI: 2.94-10.10, p<0.001) [see fig 1]. Conclusion: Although the overall risk of infectious complication rates from URSL were low, longer indwelling stent time significantly increases the risk of post-operative infections. We would recommend having the stent dwell time as short as possible and not to exceed 6 months. Our findings will help prioritise these patients in the post-COVID era.

Acute management of ureteric colic in a large tertiary centre;A re-audit and comparison to BAUS guidelines

Introduction: Considerable pressure exists to deliver timely treatment for patients with acute ureteric colic. We conducted a re-audit of our practice measured against BAUS guidelines to determine an improvement in our stone service. Patients and Methods: A prospective analysis of 130 patients admitted over 3 months (October to December 2019) with acute ureteric colic. Data was collected from records and outcomes compared to our previous audit (from 2018). Results: Patient demographics were comparable: admissions 43/month, average age 54 years, median stone size 6mm, stone location (45 % distal-, 36 % proximal-,19% mid-ureteric). Sepsis rates were identical (17%) and managed with stent insertion. For non-septic patients, 51 % (previously 59%) underwent primary treatment (36 ureteroscopy/ stent, 18 ESWL) and 49 % (previously 41%) conservative management. In theatre, primary ureteroscopy was attempted in 75% cases (previously 62%) and successful in 81%. Median time to primary ureteroscopy/stent insertion remained 24 hours;primary ESWL improved to 48 hours (previously 72 hours). Median time from stent insertion to definitive ureteroscopy was 8.9 weeks (previously 6.6 weeks). For patients managed conservatively, median time to outpatient review was 6.7 weeks (previously 5.4 weeks). For ureteric stents, 100 % were removed <2 weeks post-ureteroscopy (previously 89%). Conclusions: Increasing emergency slots for acute onsite ESWL, rates of emergency primary ureteroscopy and introducing nurse-specialist stent removal (Isiris system) have enabled us to achieve primary intervention 48 hours and stent removal <2 weeks. Prolonged waiting times for definitive ureteroscopy and outpatient review remain challenging to address, particularly in the era of COVID-19.

Where are we with understanding of COVID-19?

Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.

Dysphagia presentation and management following COVID-19: an acute care tertiary centre experience.

OBJECTIVES: As the pathophysiology of COVID-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital. RESULTS: During the first wave of the COVID-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status. CONCLUSION: Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with COVID-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.