Anatomy and Neuroscience - Research Publications

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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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    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.
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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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    Diagnostic performance of 19-gauge endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in suspected lymphoma: A prospective cohort study
    Lim, CE ; Steinfort, DP ; Irving, LB (WILEY, 2020-09)
    Introduction Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) represents a minimally invasive approach in the evaluation of mediastinal/hilar lymphadenopathy. Diagnostic performance of EBUS‐TBNA in lymphoma using standard 22‐gauge (22G) needle is limited by sample volumes that are often inadequate for histopathological assessment. Objectives To evaluate the diagnostic utility of 19‐gauge (19G) EBUS‐TBNA needle in the evaluation of suspected lymphoma. Methods We prospectively collected clinical and procedural information for patients undergoing EBUS‐TBNA with 19G needle at Royal Melbourne Hospital for investigation of mediastinal/hilar lymphadenopathy, where lymphoma was considered in the differential diagnosis. All consecutive patients between June 15, 2016 and July 10, 2019 were included. If definitive diagnosis was not achieved on EBUS‐TBNA, final diagnosis was determined through subsequent investigation or a minimum of 6 months radiologic surveillance. Results Thirty‐nine patients underwent EBUS‐TBNA using 19G needle for evaluation of suspected lymphoma. Thirteen patients had a prior diagnosis of lymphoma (33%). Lymphoma was ultimately diagnosed in 23 patients (59%). Of these, 10 had a prior diagnosis of lymphoma (43%). 19G EBUS‐TBNA demonstrated lymphoma in 19 patients, with a sensitivity of 83% (95% CI 66‐93) for detection of lymphoma. Four patients required surgical biopsy to definitively characterise lymphoma subtype. Therefore, sensitivity of 19G EBUS‐TBNA for definitive diagnosis of lymphoma was 65% (95% CI 45‐81). In patients with a prior diagnosis of lymphoma, sensitivity for definitive diagnosis of lymphoma was 80% (95% CI 48‐95). Conclusion Diagnostic performance of 19G EBUS‐TBNA appears similar to standard 22G needle in detection and definitive diagnosis of lymphoma. Further invasive testing remains necessary following non‐diagnostic EBUS‐TBNA procedures.
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    Investigation and diagnostic imaging of suspected pulmonary embolism during pregnancy and the puerperium: A review of the literature
    Tester, J ; Hammerschlag, G ; Irving, L ; Pascoe, D ; Rees, M (WILEY, 2020-08)
    Pulmonary embolism (PE) is a leading cause of maternal mortality with women at increased risk of PE during pregnancy and the early postpartum period. Clinical assessment of suspected PE during pregnancy is challenging as signs and symptoms associated with PE overlap with physiological changes of pregnancy. Clinical tests and rules commonly used to assess pre-test probability of PE were historically not well validated in the pregnant population. The challenges of clinical assessment in the pregnant and postpartum population result in a lowered threshold for diagnostic imaging. Computed tomographic pulmonary angiography (CTPA) and nuclear medicine lung scintigraphy or ventilation/perfusion (V/Q) scans are the main types of diagnostic imaging for suspected PE. Both methods are associated with small levels of ionising radiation exposure to mother and foetus. Accuracy of the diagnostic imaging tests is paramount. Haemodynamic changes of pregnancy, including increased heart rate, increased blood volume and altered flow velocity in the pulmonary arteries, may influence the quality of imaging. This comprehensive review examines the literature and evidence for the investigation and diagnostic imaging of suspected pulmonary embolism during pregnancy with CTPA and V/Q. Clinical decision-making tools, biomarkers and diagnostic imaging during pregnancy and postpartum will be considered with a focus on diagnostic accuracy and yield, radiation dose exposure (maternal-foetal) and protocol modifications. Current practice guideline recommendations and recent literature on diagnostic pathways are also presented.
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    Health impacts of bushfire smoke exposure in Australia
    Walter, CM ; Schneider-Futschik, EK ; Knibbs, LD ; Irving, LB (WILEY, 2020-05)
    Smoke exposure from bushfires, such as those experienced in Australia during 2019-2020, can reach levels up to 10 times those deemed hazardous. Short-term and extended exposure to high levels of air pollution can be associated with adverse health effects, although the most recent fires have brought into sharp focus that several important knowledge gaps remain. In this article, we briefly identify and discuss the existing Australian evidence base and make suggestions for future research.
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    Adequate tumour cellularity is essential for accurate PD-L1 immunohistochemistry assessment on cytology cell-block specimens
    Hendry, S ; Byrne, DJ ; Christie, M ; Steinfort, DP ; Irving, LB ; Wagner, C-A ; Ellwood, T ; Cooper, WA ; Fox, SB (WILEY, 2020-03)
    OBJECTIVES: PD-L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non-small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti-PD-1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD-L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. METHODS: Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD-L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. RESULTS: Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell-blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut-offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. CONCLUSIONS: PD-L1 IHC on cytology cell-block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD-L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.
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    Australian childcare centres are too close to car parks exposing children with developing lungs to high levels of traffic pollution
    Birch, H ; Walter, C ; Irving, L ; Dharmage, SC ; Smallwood, N (WILEY, 2020-12)
    OBJECTIVE: To examine the co-location of childcare centres and their outdoor play spaces with car parks in Melbourne and Sydney, Australia. METHODS: The co-location of childcare centre outdoor play spaces and car parks was examined through measurement of horizontal and vertical distances using Google Earth Pro satellite imagery. RESULTS: One hundred and forty-two childcare centres were studied in Melbourne, with 133 accompanying car parks identified. Eighty-one (57.0%) centres had a significant size car park within 150 m and 43.7% had a car park within 100 m. Twenty car parks (15.0%) were found within 10 metres of childcare centres, of which 12 (9.0%) had more than 100 spaces. Twenty centres were examined in Sydney, with 31 associated car parks identified. Eighteen childcare centres (90.0%) had car parks within 150 m and 17 (85.0%) had car parks within 100 m. CONCLUSION: Australian childcare centres are located too close to car parks exposing children to pollution and likely impacting the development of chronic respiratory disease. Traffic pollution is an avoidable risk that must be considered when planning childcare centre location. Implications for public health: The co-location of childcare centres with large-scale car parks may have long-term impacts on the respiratory health of Australian children under the age of five.
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    Reduction of COPD Hyperinflation by Endobronchial Valves Improves Intercostal Muscle Morphology on Ultrasound
    Wallbridge, P ; Hew, M ; Parry, SM ; Irving, L ; Steinfort, D (DOVE MEDICAL PRESS LTD, 2020)
    BACKGROUND AND OBJECTIVES: Parasternal intercostal ultrasound morphology reflects spirometric COPD severity. Whether this relates to the systemic nature of COPD or occurs in response to hyperinflation is unknown. We aimed to assess changes in ultrasound parasternal intercostal muscle quantity and quality (echogenicity) in response to relief of hyperinflation. We hypothesised that reduction in hyperinflation following endobronchial valve (EBV) insertion would increase ultrasound parasternal thickness and decrease echogenicity. METHODS: In this prospective cohort study, eight patients with severe COPD underwent evaluation of health-related quality of life, lung function, and sonographic thickness of 2nd parasternal intercostal muscles and diaphragm thickness, both before and after EBV insertion. Relationships between physiological and radiographic lung volumes, quality of life and ultrasound parameters were determined. RESULTS: Baseline FEV1 was 1.02L (SD 0.37) and residual volume (RV) was 202% predicted (SD 41%). Median SGRQ was 63.26 (range 20-70.6). Change in RV (-0.51 ± 0.9L) following EBV-insertion showed a strong negative correlation with change in parasternal thickness (r = -0.883) ipsilateral to EBV insertion, as did change in target lobe volume (-0.89 ± 0.6L) (r = -0.771). Parasternal muscle echogenicity, diaphragm thickness and diaphragm excursion did not significantly change. CONCLUSIONS: Dynamic changes in intercostal muscle thickness on ultrasound measurement occur in response to relief of hyperinflation. We demonstrate linear relationships between intercostal thickness and change in hyperinflation following endobronchial valve insertion. This demonstrates the deleterious effect of hyperinflation on intrinsic inspiratory muscles and provides an additional mechanism for symptomatic response to EBVs.
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    Pandemic printing: a novel 3D-printed swab for detecting SARS-CoV-2
    Williams, E ; Bond, K ; Isles, N ; Chong, B ; Johnson, D ; Druce, J ; Hoang, T ; Ballard, SA ; Hall, V ; Muhi, S ; Buising, KL ; Lim, S ; Strugnell, D ; Catton, M ; Irving, LB ; Howden, BP ; Bert, E ; Williamson, DA (WILEY, 2020-09)
    OBJECTIVES: To design and evaluate 3D-printed nasal swabs for collection of samples for SARS-CoV-2 testing. DESIGN: An iterative design process was employed. Laboratory evaluation included in vitro assessment of mock nasopharyngeal samples spiked with two different concentrations of gamma-irradiated SARS-CoV-2. A prospective clinical study compared SARS-CoV-2 and human cellular material recovery by 3D-printed swabs and standard nasopharyngeal swabs. SETTING, PARTICIPANTS: Royal Melbourne Hospital, May 2020. Participants in the clinical evaluation were 50 hospital staff members attending a COVID-19 screening clinic and two inpatients with laboratory-confirmed COVID-19. INTERVENTION: In the clinical evaluation, a flocked nasopharyngeal swab sample was collected with the Copan ESwab and a mid-nasal sample from the other nostril was collected with the 3D-printed swab. RESULTS: In the laboratory evaluation, qualitative agreement with regard to SARS-CoV-2 detection in mock samples collected with 3D-printed swabs and two standard swabs was complete. In the clinical evaluation, qualitative agreement with regard to RNase P detection (a surrogate measure of adequate collection of human cellular material) in samples collected from 50 hospital staff members with standard and 3D-printed swabs was complete. Qualitative agreement with regard to SARS-CoV-2 detection in three pairs of 3D-printed mid-nasal and standard swab samples from two inpatients with laboratory-confirmed SARS-CoV-2 was also complete. CONCLUSIONS: Using 3D-printed swabs to collect nasal samples for SARS-CoV-2 testing is feasible, acceptable to patients and health carers, and convenient.