Lung cancer screening.

Randomised controlled trials, including the National Lung Screening Trial (NLST) and the NELSON trial, have shown reduced mortality with lung cancer screening with low-dose CT compared with chest radiography or no screening. Although research has provided clarity on key issues of lung cancer screening, uncertainty remains about aspects that might be critical to optimise clinical effectiveness and cost-effectiveness. This Review brings together current evidence on lung cancer screening, including an overview of clinical trials, considerations regarding the identification of individuals who benefit from lung cancer screening, management of screen-detected findings, smoking cessation interventions, cost-effectiveness, the role of artificial intelligence and biomarkers, and current challenges, solutions, and opportunities surrounding the implementation of lung cancer screening programmes from an international perspective. Further research into risk models for patient selection, personalised screening intervals, novel biomarkers, integrated cardiovascular disease and chronic obstructive pulmonary disease assessments, smoking cessation interventions, and artificial intelligence for lung nodule detection and risk stratification are key opportunities to increase the efficiency of lung cancer screening and ensure equity of access.

"Because that is the right thing to do": A focus group study of Australian expert perspectives on offering smoking cessation support in lung cancer screening.

INTRODUCTION: Lung cancer screening (LCS) trials, targeting people with smoking history, have demonstrated reduced mortality. How to optimally embed evidence-based smoking cessation support in LCS, including in Australia, needs to be better understood. We sought experts' perspectives to identify potential barriers and effective implementation strategies. METHODS: Perceptions of providing smoking cessation support in LCS were elicited in 24 focus groups and three individual interviews with clinicians, cancer screening program managers/policymakers, and researchers during 2021. We conducted framework analysis and mapped key topics to the updated Consolidated Framework for Implementation Research. RESULTS: Experts (N=84 participants) strongly supported capitalising on an "opportune time" for smoking cessation and new LCS participant contact opportunities throughout the screening and assessment pathway. Many advocated for adapting existing cessation resources to the LCS setting and providing support without participant costs. Experts generally considered referral alone to established programs (e.g., telephone Quitline) as insufficient, but likely helpful in follow-up, and dedicated cessation specialist roles as essential. Broader cessation messaging (via mass media/community channels) was also suggested to reinforce individualised support. Experts described inherent alignment, and an ethical responsibility, to deliver smoking cessation as a core LCS component. It was suggested that LCS-eligible participants' varied experiences of stigma, health literacy, and motivation, be considered in cessation supports. Primary care support and individualised interventions were suggested to facilitate implementation. CONCLUSIONS: Experts considered smoking cessation support essential in LCS. The expert-identified and multi-level implementation strategies described here can directly inform smoking cessation-specific planning for Australia's forthcoming National LCS Program. IMPLICATIONS: The international literature includes few examples considering how best to provide smoking cessation support within a lung cancer screening (LCS) program in advance of program commencement. Our analysis, using the updated Consolidated Framework for Implementation Research, is one of the first to explore experts' perspectives within this context. Experts identified multiple implementation barriers to providing smoking cessation support within and outside of an Australian LCS program, including key work infrastructure barriers, and advocated for providing tailored interventions within this program. Our foundational work in a new targeted screening program's pre-implementation phase will allow international comparisons to be made.

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.

The TSANZ and Lung Foundation Australia 2023 landscape survey of lung cancer care across Australia and Aotearoa New Zealand.

BACKGROUND AND OBJECTIVE: Unwarranted variations in lung cancer care have been well described in both Australia and Aotearoa New Zealand, with shortfalls in hospital-based workforce and infrastructure previously demonstrated. A survey of lung cancer clinicians was performed to gain an updated understanding of current workforce and infrastructure. METHODS: An online Qualtrics survey included questions on institutional demographics, estimated lung cancer case load, multidisciplinary team (MDT) characteristics including workforce and local infrastructure. We sought to obtain one response from every institution treating lung cancer in Australia and Aotearoa New Zealand. RESULTS: Responses were received from 89 institutions, estimated to include 85% centres treating lung cancer in Australia and 100% of public hospitals in Aotearoa New Zealand. Lung cancer nurse specialist and Nuclear Medicine are poorly represented in multidisciplinary teams (MDTs) with just 34/88 (38%) institutions fulfilling recommended core workforce for MDT meetings. Case presentation is low with 32/88 (36%) regularly discussing all lung cancer patients at MDT. Metropolitan institutions appear to have a more comprehensive range of services on site, compared to non-metropolitan institutions. Few (4/88) institutions have embedded smoking cessation services. Compared to the previous 2021 Landscape Survey, thoracic surgery representation and core MDT workforce have improved, with modest change in specialist nurse numbers. CONCLUSION: This wide-reaching survey has identified persistent deficiencies and variations in lung cancer workforce and gaps in infrastructure. Multidisciplinary collaboration and care coordination are needed to ensure all patients can access timely and equitable lung cancer care.

Lung cancer (internet-based) Delphi (LUCiD): A modified eDelphi consensus process to establish Australasian clinical quality indicators for thoracic cancer.

BACKGROUND AND OBJECTIVE: Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand. METHODS: Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting. RESULTS: The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking. CONCLUSION: Twenty-seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia.

Facultatively ectoparasitic mites as vectors for entomopathogenic bacteria in Drosophila.

Opportunistic bacterial infections are common in insect populations but there is little information on how they are acquired or transmitted. We tested the hypothesis that Macrocheles mites can transmit systemic bacterial infections between Drosophila hosts. We found that 24% of mites acquired detectable levels of bacteria after feeding on infected flies and 87% of infected mites passed bacteria to naïve recipient flies. The probability that a mite could pass Serratia from an infected donor fly to a naïve recipient fly was 27.1%. These data demonstrate that Macrocheles mites are capable of serving as vectors of bacterial infection between insects.

Education messages and strategies to inform the public, potential screening candidates and healthcare providers about lung cancer screening: A systematic review.

International lung cancer screening (LCS) trials, using low-dose computed tomography, have demonstrated clinical effectiveness in reducing mortality from lung cancer. This systematic review aims to synthesise the key messages and strategies that could be successful in increasing awareness and knowledge of LCS, and ultimately increase uptake of screening. Studies were identified via relevant database searches up to January 2022. Two authors evaluated eligible studies, extracted and crosschecked data, and assessed quality. Results were synthesised narratively. Of 3205 titles identified, 116 full text articles were reviewed and 22 studies met the inclusion criteria. Twenty studies were conducted in the United States. While the study findings were heterogenous, key messages mentioned across multiple studies were about: provision of information on LCS and the recommendations for LCS (n = 8); benefits and harms of LCS (n = 6); cost of LCS and insurance coverage for participants (n = 6) and eligibility criteria (n = 5). To increase knowledge and awareness, evidence from awareness campaigns suggests that presenting information about eligibility and the benefits and harms of screening, may increase screening intention and uptake. Evidence from behavioural studies suggests that campaigns supporting engagement with platforms such as educational videos and digital awareness campaigns might be most effective. Group based learning appears to be most suited to increasing health professionals' knowledge. This systematic review found a lack of consistent evidence to demonstrate which strategies are most effective for increasing participant healthcare professional and community awareness and education about LCS.

USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study.

BACKGROUND: Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. METHODS: In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete. FINDINGS: Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 [78%] of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7-22·1%; absolute odds ratio 4·00, 95% CI 1·89-9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years [SD 5·9] vs 63·3 years [5·7]; p<0·0001), had more comorbidities (median 2 [IQR 1-3] vs 1 [1-2]; p<0·0001), and shorter life expectancy (13·9 years [95% CI 12·8-14·9] vs 14·8 [13·6-16·0] years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years [95% CI 2089·6-2425·9] vs 2000·7 years [1841·2-2160·3]; difference 247·9 years, p=0·015). INTERPRETATION: PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes. FUNDING: Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.

Contemporary Concise Review 2021: Pulmonary nodules from detection to intervention.

The US Preventive Task Force (USPSTF) has updated screening criteria by expanding age range and reducing smoking history required for eligibility; the International Lung Screen Trial (ILST) data have shown that PLCOM2012 performs better for eligibility than USPSTF criteria. Screening adherence is low (4%-6% of potential eligible candidates in the United States) and depends upon multiple system and patient/candidate-related factors. Smoking cessation in lung cancer improves survival (past prospective trial data, updated meta-analysis data); smoking cessation is an essential component of lung cancer screening. Circulating biomarkers are emerging to optimize screening and early diagnosis. COVID-19 continues to affect lung cancer treatment and screening through delays and disruptions; specific operational challenges need to be met. Over 70% of suspected malignant lesions develop in the periphery of the lungs. Bronchoscopic navigational techniques have been steadily improving to allow greater accuracy with target lesion approximation and therefore diagnostic yield. Fibre-based imaging techniques provide real-time microscopic tumour visualization, with potential diagnostic benefits. With significant advances in peripheral lung cancer localization, bronchoscopically delivered ablative therapies are an emerging field in limited stage primary and oligometastatic disease. In advanced stage lung cancer, small-volume samples acquired through bronchoscopic techniques yield material of sufficient quantity and quality to support clinically relevant biomarker assessment.

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.

Single- and Multiple-Ascending-Dose Study of the Safety, Tolerability, and Pharmacokinetics of the Polymyxin Derivative SPR206.

Carbapenem-resistant Acinetobacter baumannii and Enterobacterales are identified as urgent threats, and multidrug-resistant (MDR) Pseudomonas aeruginosa and extended-spectrum beta-lactamase (ESBL)-producing pathogens are identified as serious threats by the Centers for Disease Control and Prevention (CDC). SPR206 is a novel polymyxin derivative with potent in vitro and in vivo activity against A. baumannii, P. aeruginosa, and multiple clinically important species of Enterobacterales, including multidrug- and extensively drug-resistant strains. This was a first-in-human (FIH) double-blind, placebo-controlled, single-, and multiple-ascending-dose study of the safety, tolerability, and pharmacokinetics (PK) of SPR206 in 94 healthy subjects. Following intravenous (i.v.) administration (1-h infusion) at single doses of 10 mg to 400 mg and multiple doses of 25 mg to 150 mg every 8 h (q8h) for 7 days and 100 mg q8h for 14 days, SPR206 was generally safe and generally well tolerated. While the incidence of adverse events increased with dose, most were of mild severity. Systemic exposure (maximum concentration of drug in serum [Cmax] and area under the concentration-time curve [AUC]) to SPR206 was approximately dose proportional, time to peak concentrations ranged from 1.1 to 1.3 h, and half-life ranged from 2.4 to 4.1 h. No appreciable accumulation occurred with repeated dosing of SPR206, and trough concentrations suggest that steady state was achieved by day 2. Urinary excretion of unchanged SPR206 was dose dependent across single- (SAD) and multiple-ascending-dose (MAD) cohorts, and the percentage of dose excreted as SPR206 was up to >50%. Importantly, no evidence of nephrotoxicity was observed over 14 days of 100 mg q8h dosing of SPR206; a dosing regimen anticipated to exceed requirements for clinical efficacy. (This study has been registered at ClinicalTrials.gov under identifier NCT03792308.).

Pharmacokinetics and Tolerability of Intravenous Sulbactam-Durlobactam with Imipenem-Cilastatin in Hospitalized Adults with Complicated Urinary Tract Infections, Including Acute Pyelonephritis.

Durlobactam (DUR; ETX2514) is a novel ß-lactamase inhibitor with broad-spectrum activity against Ambler class A, C, and D ß-lactamases. Durlobactam restores the in vitro activity of sulbactam (SUL) against members of the Acinetobacter baumannii-A. calcoaceticus complex (ABC). Sulbactam (SUL)-durlobactam (SUL-DUR) is under development for the treatment of ABC infections. Eighty patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), were randomized 2:1 to receive SUL-DUR at 1 g/1 g intravenously (i.v.) or placebo every 6 h (q6h) for 7 days and background therapy with imipenem-cilastatin (IMI) at 500 mg i.v. q6h to evaluate the tolerability of SUL-DUR in hospitalized patients. Patients with bacteremia could receive up to 14 days of therapy. SUL-DUR tolerability and the values of various pharmacokinetic (PK) parameters were determined. Efficacy was recorded at the test-of-cure (TOC) visit. SUL-DUR was well tolerated, with no serious adverse events (AEs) being reported. Headache (5.7%), nausea (3.8%), diarrhea (3.8%), and vascular pain (3.8%) were the most common drug-related AEs with SUL-DUR and were mostly of mild or moderate severity. The PK profile of DUR and SUL in hospitalized patients was consistent with observations in healthy volunteers. Overall success in the microbiological modified intent-to-treat (m-MITT) population was similar between the groups, as would be expected with IMI background therapy in all patients (overall success at the TOC visit, 76.6% [n = 36] with SUL-DUR and 81.0% [n = 17] with placebo). SUL-DUR in combination with IMI was well tolerated in patients with cUTIs. The pharmacokinetics of SUL-DUR observed in hospitalized patients was similar to that observed in healthy volunteers. (This study has been registered at ClinicalTrials.gov under identifier NCT03445195.).

Electronic cigarettes: A position statement from the Thoracic Society of Australia and New Zealand.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators.

Pharmacokinetics, Safety, and Tolerability of Intravenous Durlobactam and Sulbactam in Subjects with Renal Impairment and Healthy Matched Control Subjects.

Sulbactam-durlobactam is being developed for the treatment of infections caused by Acinetobacter baumannii, including those caused by multidrug- and carbapenem-resistant isolates. This was a phase 1 study to evaluate the effects of various degrees of renal impairment, including subjects with end-stage renal disease (ESRD) on hemodialysis (HD), on the pharmacokinetics and safety profile of durlobactam (also known as ETX2514) and sulbactam after single intravenous (i.v.) dose administration. For healthy subjects and those with mild or moderate renal impairment (RI), single 1,000-mg doses each of durlobactam and sulbactam via a 3-h i.v. infusion were administered, and for severe renal impairment, 500-mg doses were administered. For subjects with ESRD and HD, 500-mg i.v. doses each of durlobactam and sulbactam were administered post-HD and pre-HD, with a 1-week washout between doses. Among 34 subjects, decreasing renal function increased systemic exposure (peak plasma concentration [Cmax] and area under the concentration-time curve [AUC]) to durlobactam and sulbactam in a generally linear manner. In healthy subjects and in those with mild or moderate renal impairment, the majority of durlobactam and sulbactam was excreted in the urine, while approximately 40% or less was excreted in urine in subjects with severe renal impairment or ESRD. In subjects with ESRD, hemodialysis was effective at removing both durlobactam and sulbactam from plasma. Renal impairment had no effect of the safety/tolerability profile of durlobactam and sulbactam. In summary, RI and ESRD had a predictable effect on the pharmacokinetic (PK) profile of durlobactam and sulbactam with no adverse effects on the safety/tolerability profile. Durlobactam and sulbactam are cleared to a similar extent by renal elimination and are impacted similarly by renal impairment. The results from this study have been used with population PK modeling and nonclinically derived PK/PD (pharmacodynamic) exposure targets to establish dosage recommendations for durlobactam and sulbactam in patients with various degrees of RI. The dosing regimen of durlobactam-sulbactam will require adjustment in patients with severe renal insufficiency and in those with ESRD.

Electronic cigarettes in physician practice: a complex debate.

E-cigarettes, or electronic nicotine delivery systems (ENDS), have been suggested as a potential aid for smoking cessation, but many questions about their efficacy and safety remain unanswered. Until very recently, the evidence for ENDS in smoking cessation was largely based on observational studies or randomised controlled trials with methodological flaws and did not provide adequate evidence to support strongly ENDS for smoking cessation. Concerns about the uptake of ENDS by nonsmoking populations (such as adolescents) remain. More recent evidence may indicate the effect of ENDS in smoking cessation, but many questions remain unanswered. In this article, we address recent claims that failure to recommend ENDS for smoking cessation represents unethical practice. We strongly dispute this claim, analysing the many complex issues that clinicians working in smoking cessation should consider.

Plasma and Intrapulmonary Concentrations of ETX2514 and Sulbactam following Intravenous Administration of ETX2514SUL to Healthy Adult Subjects.

ETX2514 is a novel ß-lactamase inhibitor that broadly inhibits Ambler class A, C, and D ß-lactamases. ETX2514 combined with sulbactam (SUL) in vitro restores sulbactam activity against Acinetobacter baumannii ETX2514-sulbactam (ETX2514SUL) is under development for the treatment of A. baumannii infections. The objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations following intravenous (i.v.) ETX2514 and sulbactam. Plasma, ELF, and AM concentrations of ETX2514 and sulbactam were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 30 healthy adult subjects following repeated dosing (ETX2514 [1 g] and sulbactam [1 g] every 6 h [q6h], as a 3-h i.v. infusion, for a total of 3 doses). A bronchoalveolar lavage (BAL) was performed once in each subject at either 1, 2.5, 3.25, 4, or 6 h after the start of the last infusion. Penetration ratios were calculated from area under the concentration-time curve from 0 to 6 h (AUC0-6) values for total plasma and ELF using mean and median concentrations at the BAL fluid sampling times. Respective ELF AUC0-6 values, based on mean and median concentrations, were 40.1 and 39.4 mg · h/liter for ETX2514 and 34.7 and 34.5 mg · h/liter for sulbactam. Respective penetration ratios of ELF to total/unbound plasma concentrations, based on mean and median AUC0-6 values, of ETX2514 were 0.37/0.41 and 0.36/0.40, whereas these same ratio values were 0.50/0.81 and 0.50/0.80 for sulbactam. ETX2514 and sulbactam concentrations in AM were measurable and fairly constant throughout the dosing interval (median values of 1.31 and 1.01 mg/liter, respectively). These data support further study of ETX2514SUL for the treatment of pneumonia caused by multidrug-resistant A. baumannii (This study has been registered at ClinicalTrials.gov under identifier NCT03303924.).

Global Sources of Fine Particulate Matter: Interpretation of PM2.5 Chemical Composition Observed by SPARTAN using a Global Chemical Transport Model.

Exposure to ambient fine particulate matter (PM2.5) is a leading risk factor for the global burden of disease. However, uncertainty remains about PM2.5 sources. We use a global chemical transport model (GEOS-Chem) simulation for 2014, constrained by satellite-based estimates of PM2.5 to interpret globally dispersed PM2.5 mass and composition measurements from the ground-based surface particulate matter network (SPARTAN). Measured site mean PM2.5 composition varies substantially for secondary inorganic aerosols (2.4-19.7 µg/m3), mineral dust (1.9-14.7 µg/m3), residual/organic matter (2.1-40.2 µg/m3), and black carbon (1.0-7.3 µg/m3). Interpretation of these measurements with the GEOS-Chem model yields insight into sources affecting each site. Globally, combustion sectors such as residential energy use (7.9 µg/m3), industry (6.5 µg/m3), and power generation (5.6 µg/m3) are leading sources of outdoor global population-weighted PM2.5 concentrations. Global population-weighted organic mass is driven by the residential energy sector (64%) whereas population-weighted secondary inorganic concentrations arise primarily from industry (33%) and power generation (32%). Simulation-measurement biases for ammonium nitrate and dust identify uncertainty in agricultural and crustal sources. Interpretation of initial PM2.5 mass and composition measurements from SPARTAN with the GEOS-Chem model constrained by satellite-based PM2.5 provides insight into sources and processes that influence the global spatial variation in PM2.5 composition.

Consensus minimum data set for lung cancer multidisciplinary teams: Results of a Delphi process.

BACKGROUND AND OBJECTIVE: While multidisciplinary team (MDT) care in lung cancer is widely practiced, there are few guidelines for MDT on best data collection strategies. MDT meetings need ready access to information for the provision of optimal treatment recommendations (the primary purpose of the meeting), audit of team performance and benchmarking. This study aimed to develop a practical data set designed for these goals through a recognized consensus process with health professionals who participate in formal MDT settings. METHODS: A modified Delphi process with three iterations (two surveys and one consensus conference) was carried out involving over 100 Australian lung cancer MDT health professionals. RESULTS: In total, 122 lung cancer MDT health professionals responded to the Round 1 survey from over 350 invitees. Of the 122, 98 were available for invitation to Round 2. Of 98, 52 (53%) invitees responded to the Round 2 survey. After two rounds, 51 data elements across 8 domains (patient demographics, risk factors, biopsy data, staging, timeliness, treatment, follow-up and patient selection) achieved consensus, defined as 80% agreement. For Round 3, 33 MDT lead clinicians were invited to participate in a consensus conference. Of 33, 14 (42%) invitees distilled the 47 data elements into 23 elements across 8 domains to address the study objectives. CONCLUSION: A practical data set for lung cancer MDT to use for optimal treatment recommendations and to evaluate team performance was developed through recognized consensus methodology. Access to streamlined, relevant and feasible data collection strategies may improve MDT decision-making, audit of team performance and facilitate benchmarking.

The Effect of Implant Type on Nipple Position Geometry and Aesthetics Following Tissue Expander Reconstruction After Nipple Sparing Mastectomy.

BACKGROUND: While recent studies have reported modest to no difference in breast aesthetics for shaped and round implant types in breast augmentations, the anatomy and biomechanics in the setting of breast reconstruction is different. OBJECTIVES: Accordingly, we endeavored to evaluate whether two implant types impacted nipple position and aesthetic features in prosthetic breast reconstruction. METHODS: A retrospective chart review was carried out on patients who underwent nipple-sparing mastectomy (NSM) with immediate tissue expander breast reconstruction. Patients were divided into two cohorts: smooth round implants and textured shaped implants. Postoperative photographs were evaluated to assess nipple displacement vis-à-vis a vector of maximal projection and aesthetic outcome for features of breast shape. RESULTS: Of 102 breasts meeting the inclusion criteria, 41 had tissue expander-implant reconstruction with anatomical shaped implants, and 61 had reconstruction with smooth round implants. The shaped implant cohort had less nipple deviation from the point of maximal projection (3.69 ± 6.24 vs 7.52 ± 10.50; P < 0.0001). Graded semi-quantitative aesthetic scores were also higher (4.04 ± 0.67 vs 3.72 ± 0.93; P = 0.0044) in the shaped implants than in the round cohort. CONCLUSIONS: Unlike breast augmentation, there is a paucity of overlying breast tissue and larger dissected spaces in prosthetic breast reconstruction. Our analysis suggests that in this setting, textured anatomic implants result in less nipple deviation from the point of maximum projection and improved aesthetic outcomes compared to round implants. When considering implant choice in NSM reconstruction, the manifold risks of shaped textured implants must thus be informed by potential aesthetic benefits with respect to shape and enhanced nipple sensation.