Effective Radiation Dose from Cone-Beam Computed Tomography Guidance during Bronchoscopic Tumour Ablation.

INTRODUCTION: Endobronchial radiofrequency ablation (RFA) is a novel minimally invasive approach to management of peripheral non-small-cell lung cancer (NSCLC) in medically inoperable patients. Minimally invasive ablative techniques are generally delivered with cone-beam computed tomography (CBCT) guidance. CBCT requires a significant number of two dimensional imaging projections to be acquired which is then reconstructed as a three-dimensional cone-beam image. The objective of this study was to determine the radiation dosimetry consequent to use of CBCT guidance for bronchoscopic RFA. METHODS: Post hoc analysis of data following bronchoscopic RFA of stage I biopsy-confirmed NSCLC performed with CBCT. Effective dose estimates for these patients were calculated using PCXMC2.0 software. RESULTS: Ten patients underwent bronchoscopic RFA, with a median 3 (range 2-4) CBCT spins per procedure. Mean dose area product (DAP) per procedure was 7,778 µGy.m2 (±4,743) with an effective dose of 11.6 mSv (±7.4). The DAP per spin for these 10 patients varied from 83.8 to 8,625.6 µGy.m2 (effective dose range 0.15-13.81 mSv). CONCLUSION: This is the first study to report radiation dosimetry consequent to CT guidance for bronchoscopic RFA procedures. Effective doses appear comparable to other CT fluoroscopic procedures.

Hemiparasite Phtheirospermum japonicum growth benefits from a second host and inflicts greater host damage with exogenous N supply.

While parasites are likely to connect to multiple host plants in nature, parasitism dynamics under multiple association conditions remain unclear and are difficult to separate from competitive effects. In this study, a five-compartment split root-box was constructed to allow a single facultative root hemiparasite, Phtheirospermum japonicum, to connect to zero, one or two Medicago sativa hosts while maintaining constant plant number and independently controlling nutrient supply. In the first experiment, we found that P. japonicum derived equal, additive benefits from attachment to a second host irrespective of parasite N status. In the second experiment, parasites were grown at four N levels in either parasitic or control conditions. Attachment caused a constant, absolute increase in parasite mass at all N levels, while host damage increased at higher parasite N levels despite an apparent decrease in host to parasite N transfer. Our findings suggest that host damage caused by P. japonicum may be strengthened by exogenous nitrogen supply to the parasite.

Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial.

BACKGROUND: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. METHODS: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. FINDINGS: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. INTERPRETATION: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. FUNDING: None.

Defensiveness Toward IAT Feedback Predicts Willingness to Engage in Anti-Bias Behaviors.

People who are more defensive about their feedback on the Race-Attitudes Implicit Association Test (IAT) are less willing to engage in anti-bias behaviors. Extending on this work, we statistically clarified defensiveness constructs to predict willingness to engage in anti-bias behaviors among people who received pro-White versus no-bias IAT feedback. We replicated the finding that U.S. Americans are generally defensive toward pro-White IAT feedback, and that more defensiveness predicts less willingness to engage in anti-bias behaviors. However, people who believed their pro-White IAT feedback was an inaccurate reflection of their "true attitudes" were more willing to engage in anti-bias behaviors compared with people who received no-bias IAT feedback. These results better illuminate the defensiveness construct suggesting that receiving self-threatening feedback about bias may motivate people's willingness to engage in anti-bias behaviors in different ways depending on how people respond to that feedback.

Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort.

BACKGROUND: Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST). METHODS: The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results. RESULTS: Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results. CONCLUSION: COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program. TRIAL REGISTRATION: NCT02871856.

Improving the reliability and validity of the IAT with a dynamic model driven by similarity.

The Implicit Association Test (IAT), like many behavioral measures, seeks to quantify meaningful individual differences in cognitive processes that are difficult to assess with approaches like self-reports. However, much like other behavioral measures, many IATs appear to show low test-retest reliability and typical scoring methods fail to quantify all of the decision-making processes that generate the overt task performance. Here, we develop a new modeling approach for IATs based on the geometric similarity representation (GSR) model. This model leverages both response times and accuracy on IATs to make inferences about representational similarity between the stimuli and categories. The model disentangles processes related to response caution, stimulus encoding, similarities between concepts and categories, and response processes unrelated to the choice itself. This approach to analyzing IAT data illustrates that the unreliability in IATs is almost entirely attributable to the methods used to analyze data from the task: GSR model parameters show test-retest reliability around .80-.90, on par with reliable self-report measures. Furthermore, we demonstrate how model parameters result in greater validity compared to the IAT D-score, Quad model, and simple diffusion model contrasts, predicting outcomes related to intergroup contact and motivation. Finally, we present a simple point-and-click software tool for fitting the model, which uses a pre-trained neural network to estimate best-fit parameters of the GSR model. This approach allows easy and instantaneous fitting of IAT data with minimal demands on coding or technical expertise on the part of the user, making the new model accessible and effective.

An Australian COVID-19 respiratory care unit experience.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a heterogeneous presentation ranging from severe pneumonitis to asymptomatic infection. International studies have demonstrated the utility of respiratory care units (RCUs) to facilitate the delivery of non-invasive ventilation techniques to patients with COVID-19 pneumonitis. AIMS: This study aims to describe the patient characteristics, flow and outcomes of admissions to the Royal Melbourne Hospital (RMH) COVID-19 RCU (CRCU) during its initial period of operation. METHODS: Single-centre retrospective cohort study, all patients admitted to CRCU between 17 September and 10 December 2021 were included in this study. Patient demographics, including comorbidities and limitations of medical treatment, were analysed. Admission source and discharge destination were reviewed. Length of stay was recorded. Finally, in-hospital and CRCU mortality were analysed. RESULTS: Ninety-seven patients, comprising 111 admissions, occurred during the study period with median age of 65 years (48% female). Most patients were admitted from and discharged to the ward. Twenty patients died in hospital (21%), with age, 4C score, comorbidity and presence of obstructive lung disease predicting mortality (area under the curve (AUC) 0.85, P < 0.001). Mortality was significantly higher in those over 65 years of age compared to those under 65 (P < 0.001), or those deemed not for intubation compared to those for intubation (P = 0.0019). CONCLUSIONS: This study demonstrates the feasibility of operating a CRCU within an Australian tertiary healthcare setting.

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer.

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Comparison of Changes in Pulmonary Function After Stereotactic Body Radiation Therapy Versus Conventional 3-Dimensional Conformal Radiation Therapy for Stage I and IIA Non-Small Cell Lung Cancer: An Analysis of the TROG 09.02 (CHISEL) Phase 3 Trial.

PURPOSE: The TROG 09.02 CHISEL trial compared conventional radiation therapy (CRT) with stereotactic body radiation therapy (SBRT) in patients with inoperable early-stage non-small cell lung cancer. Patients randomized to SBRT had less local failure and improved overall survival. This analysis reports differences in pulmonary function tests (PFTs) and the 6-minute walk test (SMWT) between patients who received SBRT and those who received CRT. METHODS AND MATERIALS: We analyzed the PFTs and SMWTs of all patients recruited to the CHISEL [trial. During this trial, patients underwent serial PFTs. Linear regression models were used to compare parameters between SBRT and CRT at 3 and 12 months after treatment. RESULTS: One hundred and one patients were enrolled; 33 patients were treated with CRT, 61 were treated with SBRT, and 7 did not receive treatment. Primary tumor size was similar between arms: SBRT 25 mm (standard deviation [SD], 9) and CRT 28 mm (SD, 9). On regression analysis, at 3 and 12 months, there was no evidence of a difference between arms in PFT decline or distance walked in the SMWT. Planning target volume size was significantly larger in the CRT arm, 142.79 cc (SD, 61.14), compared with the SBRT group, 46.15 cc (SD, 23.39). The mean biologically effective dose received by the target was significantly larger in the SBRT group, 125.92 Gy (SD, 21.58), compared with CRT, 65.49 Gy (SD, 6.32). Mean dose to the lungs minus the gross target volume incorporating motion was 8.9 Gy (SD, 2.34) in the CRT group and 4.37 Gy (SD, 1.42) in the SBRT group. CONCLUSIONS: Despite the considerably higher biologically effective doses delivered to the tumor in SBRT, there was no difference in decline in respiratory function observed between the 2 groups.

Prime-boost, double-dose influenza vaccine immunity in COPD: a pilot observational study.

Background: COPD patients are more susceptible to viral respiratory infections and their sequelae, and have intrinsically weaker immune responses to vaccinations against influenza and other pathogens. Prime-boost, double-dose immunisation has been suggested as a general strategy to overcome weak humoral response to vaccines, such as seasonal influenza vaccination, in susceptible populations with weak immunity. However, this strategy, which may also provide fundamental insights into the nature of weakened immunity, has not been formally studied in COPD. Methods: We conducted an open-label study of seasonal influenza vaccination in 33 vaccine-experienced COPD patients recruited from established cohorts (mean age 70 (95% CI 66.9-73.2) years; mean forced expiratory volume in 1 s/forced vital capacity ratio 53.4% (95% CI 48.0-58.8%)). Patients received two sequential standard doses of the 2018 quadrivalent influenza vaccine (15 µg haemagglutinin per strain) in a prime-boost schedule 28 days apart. We measured strain-specific antibody titres, an accepted surrogate of likely efficacy, and induction of strain-specific B-cell responses following the prime and boost immunisations. Results: Whereas priming immunisation induced the expected increase in strain-specific antibody titres, a second booster dose was strikingly ineffective at further increasing antibody titres. Similarly, priming immunisation induced strain-specific B-cells, but a second booster dose did not further enhance the B-cell response. Poor antibody responses were associated with male gender and cumulative cigarette exposure. Conclusions: Prime-boost, double-dose immunisation does not further improve influenza vaccine immunogenicity in previously vaccinated COPD patients. These findings underscore the need to design more effective vaccine strategies for COPD patients for influenza.

Safety and Feasibility of a Novel Externally Cooled Bronchoscopic Radiofrequency Ablation Catheter for Ablation of Peripheral Lung Tumours: A First-In-Human Dose Escalation Study.

BACKGROUND: Radiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode. OBJECTIVES: The objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC. METHODS: Patients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distribution/uniformity of ablation and efficacy of tumour ablation. RESULTS: RFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 = 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ). CONCLUSION: Bronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.

Post-acute COVID-19 condition (PACC): a perspective on collaborative Australian research imperatives and primary health models of care.

Post-acute COVID-19 condition (PACC) - also known as long COVID - is a serious and growing problem in primary health. This letter describes the work of the Victorian Post-Acute COVID-19 Study (VPACS) group, which comprises clinician researchers, basic scientists and consumers. Two key priorities for PACC research in Australia are identified and discussed: (1) the establishment of COVID-19 patient registries and data linkage; and (2) the consolidation of clinical guidelines. Collaboration between consumers, researchers, clinicians and institutions must be the foundation of PACC management in Australia. Ongoing research should focus on large, multicentre controlled studies, the protective effect of vaccination, differential impacts from variants, pathobiological underpinnings, disease mechanisms to avoid severe and enduring impacts on the Australian economy. The lived experience of people with PACC is also essential to enable the design and implementation of effective models of care. VPACS brings a diverse group of people together to work on a shared vision of holistic and high-quality care, and collectively maximise their impact on outcomes for patients and the broader community.

Diagnostic imaging for suspected pulmonary embolism during pregnancy and postpartum: A comparative radiation dose study.

INTRODUCTION: To compare the radiation dose exposure and diagnostic efficiency of computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion imaging (V/Q) for clinically suspected pulmonary embolism (PE) in pregnant and postpartum women in a tertiary hospital setting. METHODS: A retrospective cohort study of 473 pregnant and postpartum women referred for CTPA or V/Q for clinically suspected PE between January 2013 and December 2018 at a tertiary hospital. Maternal effective radiation dose, breast-absorbed radiation dose and fetal-absorbed dose estimates were calculated. Diagnostic yield was evaluated from radiological findings. RESULTS: Computed tomographic pulmonary angiography (CTPA) was more commonly used for the imaging of suspected PE in pregnant and postpartum populations (51.9% vs. 48.1% and 77.1% vs. 22.9%, respectively). CTPA was associated with higher maternal effective and breast-absorbed doses (maternal effective CTPA 4.7 (±2.9) mSv (millisievert), V/Q 1.7(±0.8) mSv (mean difference 2.93 mSv P < 0.001), and breast-absorbed CTPA 8.0 (±5.2) mGy (milligray), V/Q 0.3 (±0.1) (mean difference 7.67 mGy P < 0.001), respectively). Fetal radiation dose exposure was low. The incidence of positive PE was 5.5%. Indeterminate rates of CTPA and V/Q were 3.0% and 5.5% (P = 0.176), respectively. CONCLUSIONS: Compared to V/Q, CTPA is associated with higher maternal and breast radiation dose; however, modern CT scanners achieve lower radiation doses than historically described. Fetal radiation dose was comparably low. The diagnostic yield of the imaging modalities in pregnant and postpartum women is similar. Revision of guidelines should occur with the advances in CT technology.

Knowledge and Attitudes of Allied Health Professionals Towards End-Of-Life and Advance Care Planning Discussions With People With COPD: A Cross-Sectional Survey Study.

Chronic obstructive pulmonary disease (COPD) is a progressive, life-limiting condition. End-of-life (EOL) and Advance Care Planning (ACP) discussions are essential, yet access and support remain inadequate. Allied health professionals (AHPs) commonly have ongoing relationships with patients and opportunities to discuss care outside acute crises as is considered best practice. Australian and New Zealand AHPs were invited to complete an anonymous, online, cross-sectional survey that aimed to explore knowledge, attitudes and practices, and associated perceived triggers and barriers to EOL and ACP discussions with patients with COPD. Closed survey responses were summarized descriptively and free-text thematically analysed. One hundred and one AHPs (physiotherapists, social workers and occupational therapists) participated. Many held positive attitudes towards ACP but lacked procedural knowledge. Half (50%) of participants routinely discussed EOL care with patients when perceiving this to be appropriate but only 21% actually discussed ACP with the majority of their patients. Many cited lack of training to engage in sensitive EOL discussions, with barriers including: 1) clinician lack of confidence/fear of distressing patients (75%); 2) perceived patient and family reluctance (51%); 3) organizational challenges (28%); and 4) lack of role clarity (39%). AHPs commonly have ongoing relationships with patients with chronic conditions but lack the confidence and role clarity to utilise this position to engage ongoing EOL and ACP discussions. While AHPs may not traditionally consider EOL and ACP discussions as part of their role, it is crucial that they feel prepared to respond if patients broach the topic.

Stigma Toward Consensual Non-Monogamy: Thematic Analysis and Minority Stress.

Consensually non-monogamous (CNM) romantic and sexual relationships tend to be stigmatized. The present research examined this stigma across two studies. First, we qualitatively explored the specific ways that people in CNM relationships report experiencing stigma using thematic analysis and identified the following four themes: Expressions of discomfort/disapproval of CNM, Loss of resources/threatening behaviors, Character devaluation, and Relationship devaluation (Study 1; N = 372). Second, we examined the relationship between experienced stigma and psychological well-being for people in CNM relationships, using the framework of minority stress theory. We found that experienced stigma was positively associated with psychological distress and that this association was partially statistically mediated by anticipated stigma and internalized stigma (Study 2; N = 383). Overall, this research strives to achieve a better understanding of the processes and potential consequences of stigma toward CNM relationships and individuals.

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.

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.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

BACKGROUND: Lung cancer is the most common cause of cancer-related death in the world, however lung cancer screening has not been implemented in most countries at a population level. A previous Cochrane Review found limited evidence for the effectiveness of lung cancer screening with chest radiography (CXR) or sputum cytology in reducing lung cancer-related mortality, however there has been increasing evidence supporting screening with low-dose computed tomography (LDCT).  OBJECTIVES: To determine whether screening for lung cancer using LDCT of the chest reduces lung cancer-related mortality and to evaluate the possible harms of LDCT screening. SEARCH METHODS: We performed the search in collaboration with the Information Specialist of the Cochrane Lung Cancer Group and included the Cochrane Lung Cancer Group Trial Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, current issue), MEDLINE (accessed via PubMed) and Embase in our search. We also searched the clinical trial registries to identify unpublished and ongoing trials. We did not impose any restriction on language of publication. The search was performed up to 31 July 2021.  SELECTION CRITERIA: Randomised controlled trials (RCTs) of lung cancer screening using LDCT and reporting mortality or harm outcomes.  DATA COLLECTION AND ANALYSIS: Two review authors were involved in independently assessing trials for eligibility, extraction of trial data and characteristics, and assessing risk of bias of the included trials using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. Primary outcomes were lung cancer-related mortality and harms of screening. We performed a meta-analysis, where appropriate, for all outcomes using a random-effects model. We only included trials in the analysis of mortality outcomes if they had at least 5 years of follow-up. We reported risk ratios (RRs) and hazard ratios (HRs), with 95% confidence intervals (CIs) and used the I2 statistic to investigate heterogeneity.  MAIN RESULTS: We included 11 trials in this review with a total of 94,445 participants. Trials were conducted in Europe and the USA in people aged 40 years or older, with most trials having an entry requirement of ≥ 20 pack-year smoking history (e.g. 1 pack of cigarettes/day for 20 years or 2 packs/day for 10 years etc.). One trial included male participants only. Eight trials were phase three RCTs, with two feasibility RCTs and one pilot RCT. Seven of the included trials had no screening as a comparison, and four trials had CXR screening as a comparator. Screening frequency included annual, biennial and incrementing intervals. The duration of screening ranged from 1 year to 10 years. Mortality follow-up was from 5 years to approximately 12 years.  None of the included trials were at low risk of bias across all domains. The certainty of evidence was moderate to low across different outcomes, as assessed by GRADE. In the meta-analysis of trials assessing lung cancer-related mortality, we included eight trials (91,122 participants), and there was a reduction in mortality of 21% with LDCT screening compared to control groups of no screening or CXR screening (RR 0.79, 95% CI 0.72 to 0.87; 8 trials, 91,122 participants; moderate-certainty evidence). There were probably no differences in subgroups for analyses by control type, sex, geographical region, and nodule management algorithm. Females appeared to have a larger lung cancer-related mortality benefit compared to males with LDCT screening. There was also a reduction in all-cause mortality (including lung cancer-related) of 5% (RR 0.95, 95% CI 0.91 to 0.99; 8 trials, 91,107 participants; moderate-certainty evidence).  Invasive tests occurred more frequently in the LDCT group (RR 2.60, 95% CI 2.41 to 2.80; 3 trials, 60,003 participants; moderate-certainty evidence). However, analysis of 60-day postoperative mortality was not significant between groups (RR 0.68, 95% CI 0.24 to 1.94; 2 trials, 409 participants; moderate-certainty evidence).  False-positive results and recall rates were higher with LDCT screening compared to screening with CXR, however there was low-certainty evidence in the meta-analyses due to heterogeneity and risk of bias concerns. Estimated overdiagnosis with LDCT screening was 18%, however the 95% CI was 0 to 36% (risk difference (RD) 0.18, 95% CI -0.00 to 0.36; 5 trials, 28,656 participants; low-certainty evidence). Four trials compared different aspects of health-related quality of life (HRQoL) using various measures. Anxiety was pooled from three trials, with participants in LDCT screening reporting lower anxiety scores than in the control group (standardised mean difference (SMD) -0.43, 95% CI -0.59 to -0.27; 3 trials, 8153 participants; low-certainty evidence). There were insufficient data to comment on the impact of LDCT screening on smoking behaviour.  AUTHORS' CONCLUSIONS: The current evidence supports a reduction in lung cancer-related mortality with the use of LDCT for lung cancer screening in high-risk populations (those over the age of 40 with a significant smoking exposure). However, there are limited data on harms and further trials are required to determine participant selection and optimal frequency and duration of screening, with potential for significant overdiagnosis of lung cancer. Trials are ongoing for lung cancer screening in non-smokers.

Surveillance for severe influenza and COVID-19 in patients admitted to sentinel Australian hospitals in 2020: the Influenza Complications Alert Network (FluCAN).

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.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2019: the Influenza Complications Alert Network (FluCAN).

Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Cases were defined as patients hospitalised at any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 1 April to 31 October 2019 (the 2019 influenza season), there were 4,154 patients admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 44% were elderly (≥ 65 years), 21% were children (< 16 years), 7.7% were Aboriginal and Torres Strait Islander peoples, 1.7% were pregnant and 73% had chronic comorbidities. Most admissions were due to influenza A infection (85%). Estimated vaccine coverage was 75% in the elderly, 49% in non-elderly adults with medical comorbidities, and 27% in young children (< 5 years). The estimated vaccine effectiveness in the target adult population was 42% (95% confidence interval [95% CI]: 36%, 49%). There were a larger number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2019 than in 2018.

Sustaining the Australian respiratory workforce through the COVID-19 pandemic: a scoping literature review.

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.