Anatomy and Neuroscience - Research Publications

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    Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study
    Steinfort, DP ; Siva, S ; Rangamuwa, K ; Lee, P ; Fielding, D ; Nguyen, P ; Jennings, BR ; Yo, S ; Hardcastle, N ; Kothari, G ; Crombag, L ; Annema, J ; Yasufuku, K ; Ost, DE ; Irving, LB (BMC, 2022-09-24)
    BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.
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    Sustaining the Australian respiratory workforce through the COVID-19 pandemic: a scoping literature review
    Stone, E ; Irving, LB ; Tonga, KO ; Thompson, B (WILEY, 2022-07)
    The outbreak of the COVID-19 pandemic in late 2019 and in 2020 presented challenges to healthcare workers (HCW) around the world that were unexpected and dramatic. The relentless progress of infection, starting in China and rapidly spreading to Europe, North America and elsewhere gave more remote countries, like Australia, time to prepare but also time for unease. HCW everywhere had to readjust and change their work practices to cope. Further waves of infection and transmission with newer variants pose challenges to HCW and health systems, even after mass vaccination. Respiratory medicine HCW found themselves at the frontline, developing critical care services to support intensive care units and grappling with unanticipated concerns about safety, risk and the need to retrain. Several studies have addressed the need for rapid changes in the healthcare workforce for COVID-19 and the impact of this preparation on HCW themselves. In this paper, we present a scoping review of the literature on preparing HCW for the pandemic, explore the Australian experience of building the respiratory workforce and propose evidence-based recommendations to sustain this workforce in an unprecedented high-risk environment.
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    Communicable Diseases Intelligence Surveillance for severe influenza and COVID-19 in patients admitted to sentinel Australian hospitals in 2020: the Influenza Complications Alert Network (FluCAN)
    Begum, H ; Dwyer, DE ; Holmes, M ; Irving, L ; Simpson, G ; Senenayake, S ; Korman, T ; Friedman, ND ; Cooley, L ; Wark, P ; Bowler, S ; Kok, J ; Upham, J ; Fatovich, DM ; Waterer, G ; Macartney, K ; Blyth, CC ; Crawford, N ; Buttery, J ; Marshall, HS ; Clark, JE ; Francis, JR ; Kotsimbos, T ; Kelly, P ; Cheng, A (AUSTRALIAN GOVERNMENT, DEPT HEALTH & AGEING, 2022-03-28)
    INTRODUCTION: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. METHODS: The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. RESULTS: There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. DISCUSSION: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.
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    Hospitalisation, morbidity and outcomes associated with respiratory syncytial virus compared with influenza in adults of all ages
    Leaver, B ; Smith, B ; Irving, L ; Johnson, D ; Tong, S (WILEY, 2022-05)
    BACKGROUND: Respiratory syncytial virus (RSV) is understood to be a cause of significant disease in older adults and children. Further analysis of RSV in younger adults may reveal further insight into its role as an important pathogen in all age groups. METHODS: We identified, through laboratory data, adults who tested positive for either influenza or RSV between January 2017 and June 2019 at a single Australian hospital. We compared baseline demographics, testing patterns, hospitalisations and outcomes between these groups. RESULTS: Of 1128 influenza and 193 RSV patients, the RSV cohort was older (mean age 54.7 vs. 64.9, p < 0.001) and was more comorbid as determined by the Charlson Comorbidity Index (2.4 vs. 3.2, p < 0.001). For influenza hospitalisations, the majority admitted were aged under 65 which was not the case for RSV (61.8% vs. 45.6%, p < 0.001). Testing occurred later in RSV hospitalisations as measured by the proportion tested in the emergency department (ED) (80.3% vs. 69.2%, p < 0.001), and this was strongly associated with differences in presenting phenotype (the presence of fever). RSV was the biggest predictor of 6-month representation, with age and comorbidities predicting this less strongly. CONCLUSION: RSV is a significant contributor to morbidity and hospitalisation, sometimes outweighing that of influenza, and is not limited to elderly cohorts. Understanding key differences in the clinical syndrome and consequent testing paradigms may allow better detection and potentially treatment of RSV to reduce individual morbidity and health system burden. This growing area of research helps quantify the need for directed therapies for RSV.
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    Vaccine strain affects seroconversion after influenza vaccination in COPD patients and healthy older people
    Snape, N ; Anderson, GP ; Irving, LB ; Jarnicki, AG ; Hurt, AC ; Collins, T ; Xi, Y ; Upham, JW (NATURE PORTFOLIO, 2022-01-24)
    Though clinical guidelines recommend influenza vaccination for chronic obstructive pulmonary disease (COPD) patients and other high-risk populations, it is unclear whether current vaccination strategies induce optimal antibody responses. This study aimed to identify key variables associated with strain-specific antibody responses in COPD patients and healthy older people. 76 COPD and 72 healthy participants were recruited from two Australian centres and inoculated with influenza vaccine. Serum strain-specific antibody titres were measured pre- and post-inoculation. Seroconversion rate was the primary endpoint. Antibody responses varied between vaccine strains. The highest rates of seroconversion were seen with novel strains (36-55%), with lesser responses to strains included in the vaccine in more than one consecutive year (27-33%). Vaccine responses were similar in COPD patients and healthy participants. Vaccine strain, hypertension and latitude were independent predictors of seroconversion. Our findings reassure that influenza vaccination is equally immunogenic in COPD patients and healthy older people; however, there is room for improvement. There may be a need to personalise the yearly influenza vaccine, including consideration of pre-existing antibody titres, in order to target gaps in individual antibody repertoires and improve protection.
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    P138 Nocturnal oxygen desaturation and MET call criteria during in-laboratory sleep studies
    Stonehouse, J ; Perkins, A ; Irving, L ; Goldin, J ; Wallbridge, P ; Hii, S ; Rees, M ; Manser, R ; Kee, K (Oxford University Press (OUP), 2021-10-07)
    Abstract Introduction Patients undergoing sleep studies can experience frequent and profound oxygen desaturation. Most hospitals have standard MET (Medical Emergency Team) call criteria which obligate a response to severe oxygen desaturation. At our tertiary institution this is “Pulse oximetry/oxygen saturation: &lt; 90 despite oxygen administration”. For most sleep studies provision of oxygen overnight would not be appropriate. We sought to examine the proportion of our sleep study patients who would meet MET call criteria. Method We retrospectively examined the data of all sleep studies which were performed in our laboratory between 01/01/2021 and 30/04/2021. Demographic and pulse oximetry data was collected. Results We collected data from 448 studies (95 CPAP, 342 diagnostic, 9 Split, 2 other). Patients were 40% female, 49±15 (mean±SD) years old and had a median AHI of 10 events per hour. 290 (65%) patients had a nadir SpO2 of &lt;90%. The percentage of patients below with nadir SpO2 of 80%, 70%, 60% and 50% was 20%, 9%, 5% and 3% respectively. These proportions did not significantly change if treatment studies were excluded. In contrast, 23 (5%) of patients had a mean overnight SpO2 &lt; 90%. During the period studied no serious adverse event was recorded. Discussion Most patients presenting for a sleep study to our tertiary institution would potentially meet standard hospital MET call criteria. This demonstrates the need for hospitals to be flexible in terms of hospital wide protocols when it comes to sleep laboratories. Evidence based criteria for medical escalation in sleep laboratories are required.
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    Effect of a postoperative home-based exercise and self-management programme on physical function in people with lung cancer (CAPACITY): protocol for a randomised controlled trial
    Granger, CL ; Edbrooke, L ; Antippa, P ; Wright, G ; McDonald, CF ; Lamb, KE ; Irving, L ; Krishnasamy, M ; Abo, S ; Whish-Wilson, GA ; Truong, D ; Denehy, L ; Parry, SM (BMJ PUBLISHING GROUP, 2022-01)
    INTRODUCTION: Exercise is important in the postoperative management of lung cancer, yet no strong evidence exists for delivery of home-based programmes. Our feasibility (phase I) study established feasibility of a home-based exercise and self-management programme (the programme) delivered postoperatively. This efficacy (phase II) study aims to determine whether the programme, compared with usual care, is effective in improving physical function (primary outcome) in patients after lung cancer surgery. METHODS AND ANALYSIS: This will be a prospective, multisite, two-arm parallel 1:1, randomised controlled superiority trial with assessors blinded to group allocation. 112 participants scheduled for surgery for lung cancer will be recruited and randomised to usual care (no exercise programme) or, usual care plus the 12-week programme. The primary outcome is physical function measured with the EORTC QLQ c30 questionnaire. Secondary outcomes include health-related quality of life (HRQoL); exercise capacity; muscle strength; physical activity levels and patient reported outcomes. HRQoL and patient-reported outcomes will be measured to 12 months, and survival to 5 years. In a substudy, patient experience interviews will be conducted in a subgroup of intervention participants. ETHICS AND DISSEMINATION: Ethics approval was gained from all sites. Results will be submitted for publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12617001283369.
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    Aerosol generation related to respiratory interventions and the effectiveness of a personal ventilation hood.
    McGain, F ; Humphries, RS ; Lee, JH ; Schofield, R ; French, C ; Keywood, MD ; Irving, L ; Kevin, K ; Patel, J ; Monty, J (College of Intensive Care Medicine of Australia and New Zealand, 2020-09)
    OBJECTIVE: To quantify aerosol generation from respiratory interventions and the effectiveness of their removal by a personal ventilation hood. DESIGN AND SETTING: Determination of the aerosol particle generation (in a single, healthy volunteer in a clean room) associated with breathing, speaking, wet coughing, oxygen (O2) 15 L/min via face mask, O2 60 L/min via nasal prongs, bilevel non-invasive positive-pressure ventilation (BiPAP) and nebulisation with O2 10 L/min. INTERVENTIONS: Aerosol generation was measured with two particle sizer and counter devices, focusing on aerosols 0.5-5 μm (human-generated aerosols), with and without the hood. An increase from baseline of less than 0.3 particles per mL was considered a low level of generation. MAIN OUTCOME MEASURES: Comparisons of aerosol generation between different respiratory interventions. Effectiveness of aerosol reduction by a personal ventilation hood. RESULTS: Results for the 0.5-5 μm aerosol range. Quiet breathing and talking demonstrated very low increase in aerosols (< 0.1 particles/mL). Aerosol generation was low for wet coughing (0.1 particles/mL), O2 15 L/min via face mask (0.18 particles/mL), and high flow nasal O2 60 L/min (0.24 particles/mL). Non-invasive ventilation generated moderate aerosols (29.7 particles/mL) and nebulisation very high aerosols (1086 particles/mL); the personal ventilation hood reduced the aerosol counts by 98% to 0.5 particles/mL and 8.9 particles/mL respectively. CONCLUSIONS: In this human volunteer study, the administration of O2 15 L/min by face mask and 60 L/min nasal therapy did not increase aerosol generation beyond low levels. Non-invasive ventilation caused moderate aerosol generation and nebulisation therapy very high aerosol generation. The personal ventilation hood reduced the aerosol counts by at least 98%.
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    Effectiveness of portable air filtration on reducing indoor aerosol transmission: preclinical observational trials
    Lee, JH ; Rounds, M ; McGain, F ; Schofield, R ; Skidmore, G ; Wadlow, I ; Kevin, K ; Stevens, A ; Marshall, C ; Irving, L ; Kainer, M ; Buising, K ; Monty, J (W B SAUNDERS CO LTD, 2022-01)
    BACKGROUND: While the range of possible transmission pathways of severe acute respiratory syndrome coronavirus-2 in various settings has been investigated thoroughly, most authorities have recently acknowledged the role of aerosol spread in its transmission, especially in indoor environments where ventilation is poor. Engineering controls are needed to mitigate aerosol transmission in high-risk settings including hospital wards, classrooms and offices. AIM: To assess the effectiveness of aerosol filtration by portable air cleaning devices with high-efficiency particulate air filters used in addition to a standard building heating ventilation and air conditioning (HVAC) system. METHODS: Test rooms, including a single-bed hospital room, were filled with test aerosol to simulate aerosol movement. Aerosol counts were measured over time with various portable air cleaning devices and room ventilation systems to quantify the overall aerosol clearance rate. FINDINGS: Portable air cleaning devices were very effective for removal of aerosols. The aerosols were cleared five times faster in a small control room with portable air cleaning devices than in the room with HVAC alone. The single-bed hospital room had an excellent ventilation rate (∼14 air changes per hour) and cleared the aerosols in 20 min. However, with the addition of two air cleaning devices, the clearance time was three times faster. CONCLUSIONS: Inexpensive portable air cleaning devices should be considered for small and enclosed spaces in healthcare settings, such as inpatient rooms and personal protective equipment donning/doffing stations. Portable air cleaning devices are particularly important where there is limited ability to reduce aerosol transmission with building HVAC ventilation.
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    Pulmonary function testing for the early detection of drug-induced lung disease: a systematic review in adults treated with drugs associated with pulmonary toxicity
    Bui, A ; Han, S ; Alexander, M ; Toner, G ; Irving, L ; Manser, R (WILEY, 2020-11)
    Pulmonary function tests (PFT) are sometimes monitored during treatment with known pulmonary toxic drugs to detect asymptomatic drug-induced interstitial lung disease (DILD). We conducted a systematic review to assess the accuracy of PFT, including the diffusing capacity for carbon monoxide (DLCO), for early detection of DILD in a range of drugs. Using a pre-specified, registered review protocol, OvidMEDLINE and EMBASE were searched from 1946 to February 2018. Two reviewers independently screened abstracts and reviewed full-text articles for inclusion. Included studies were assessed for risk of bias using adapted QUADAS-2 domains and primary outcome data were extracted and entered into RevMan5 to estimate sensitivity and specificity with 95% confidence intervals (CI). The search identified 4065 citations and included 42 studies. The most commonly studied drugs were bleomycin and amiodarone. Due to clinical heterogeneity between studies, a pooled analysis was not performed. Sensitivity of monitoring with DLCO varied between 0 and 100%, with the majority of studies finding a sensitivity of <80%. CI were wide for the majority of studies. Specificity was less than 90% in all studies. Risk of bias was high for the majority of studies for the quality domain of reference standard. The findings of this review do not support routine PFT for early detection of DILD. Due to methodological limitations, the relatively small number of participants and the low prevalence of DILD in the included studies, there remains significant uncertainty about the sensitivity of PFT to screen for DILD.