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The article offers information on a study that used a case-finding method to identify adults in the community with respiratory symptoms but without a diagnosed lung disease. Topics include the study's methodology, which involved enrollment in a randomized trial to determine if early diagnosis and treatment reduce health care utilization and improve outcomes, and the results, which showed lower health care utilization.

Background: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP., Methods: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve., Results: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty., Conclusion: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment., (© 2024. The Author(s).)

Obstructive airway disease is associated with sleep disturbances. We aimed to assess the relationship between lung function and sleep disorder symptoms using cross-sectionally collected data between March 2017 and August 2021 from the Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study, a prospective community-based multi-site case-finding study. Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study participants with respiratory symptoms but without diagnosed lung disease who completed spirometry and the Global Sleep Assessment Questionnaire were included. We conducted multivariate linear regression models for forced expiratory volume in 1 s, forced vital capacity and forced expiratory volume in 1 s/forced vital capacity by Global Sleep Assessment Questionnaire responses adjusted for confounders. The same models were employed to examine respiratory symptoms, as reported on the St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test, by Global Sleep Assessment Questionnaire responses. Logistic regression models were used to assess the association of undiagnosed obstructive airway disease with sleep symptoms. Amongst 2093 adults included in the study, 48.3% were female and the median age was 63 years (interquartile range 53-72). Two-hundred and five (9.79%) subjects met spirometry criteria for undiagnosed chronic obstructive pulmonary disease, and 191 (9.13%) for undiagnosed asthma. There were no significant associations between spirometry measures and sleep symptoms (p > 0.5), controlling for age, sex, body mass index, smoking and comorbidities. Those with undiagnosed asthma were more likely to report insomnia "at least sometimes" versus "never" (odds ratio 2.58, 95% confidence interval: 1.27-6.19, p = 0.02). Respiratory symptoms were associated with sleep symptoms, with significant (p < 0.05) increases in St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test scores in those reporting most sleep symptoms. Overall, we found an association between undiagnosed asthma and insomnia, and between respiratory and sleep disorder symptoms., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: We investigated dyspnea; its associated risk factors; and its impact on health care utilization, quality of life, and work productivity in adults with undiagnosed respiratory symptoms., Research Question: What is the impact of dyspnea in adults with undiagnosed respiratory symptoms?, Study Design and Methods: This population-based study included 2,857 adults who were experiencing respiratory symptoms. These individuals had not been previously diagnosed with any lung conditions and were recruited from 17 Canadian centers using random digit dialing. Each participant underwent spirometry testing both before and after using a bronchodilator to determine if they met the diagnostic criteria for COPD, asthma, or preserved ratio impaired spirometry (PRISm), or if their spirometry results were normal. An age-matched control group (n = 231) was similarly recruited using random digit dialing. A dyspnea impact assessment score from 0 to 100 was produced using questions from the COPD Assessment Test and St. George's Respiratory questionnaire., Results: Individuals with PRISm (n = 172) reported more impactful dyspnea (mean score, 63.0; 95% CI, 59.5-66.4) than those with undiagnosed asthma (n = 265; mean score, 56.6; 95% CI, 53.9-59.3) or undiagnosed COPD (n = 330; mean score, 57.5; 95% CI, 55.1-59.9). All groups reported significantly more impactful dyspnea than the control group (mean score, 13.8; 95% CI, 11.8-15.7). Patient-specific risk factors including age, sex, BMI, smoking, and comorbidities explained 20.6% of the variation in dyspnea. An additional 12.4% of the variation was explained by disease classification and another 1.7% by the severity of lung function impairment assessed with spirometry. After adjusting for age, sex, and BMI, greater dyspnea impact was associated with increased health care utilization, lower quality of life, and reduced work productivity., Interpretation: Our findings showed that in community-based adults with undiagnosed respiratory symptoms, those identified with PRISm experienced the greatest impact of dyspnea. Dyspnea imposes burdens on the health care system and is associated with impaired quality of life and work productivity., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC., Methods: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses., Results: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017)., Conclusions: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective., Competing Interests: Disclosure JDS has received honoraria and consulting fees from Roche, Merck, BMS, AstraZeneca, Regeneron, Novartis, Protalix Biotherapeutics, Xenetic Biosciences and Protalix Biotherapeutics. JS also received grants to his institution from Roche, AstraZeneca, Protalix Biotherapeutics, CLS Therapeutics, BMS and Merck. BS received speakers’ fees from AstraZeneca, Medscape, and PEER VIEW, and consulting fees from AstraZeneca. SO received honoraria from Astra Zeneca, Bayer, BMS, and Novocure., (Copyright © 2023. Published by Elsevier Inc.)

Background: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively., Methods: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression., Results: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik ( n = 71) and 720 (95% CI 536-1208) days for Montréal residents ( n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik ( n = 24) and 270 (95% CI 194-766) days for Montréal residents ( n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41)., Interpretation: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents., Competing Interests: Competing interests: Sarah MacIsaac reports fellowship training grants from Janssen Pharmaceuticals and Boehringer Ingelheim, payment or honoraria from Boehringer Ingelheim, participation on a board for Boehringer Ingelheim, and a role on a Canadian Thoracic Society equity, diversity, and inclusion committee. Nathalie Boulanger is director of professional services, Ungava Tulattavik Health Centre. Nicole Ezer reports grants from Canadian Institutes of Health Research (CIHR), MUHC (McGill University Health Centre) Foundation, and Fonds de recherche du Québec – Santé; consulting fees from the GSK Advisory Board for chronic obstructive pulmonary disease (COPD); speaker fees for AstraZeneca family practice clinic teaching on COPD; speaker fees for GSK family practice clinic teaching on spirometry; and advisor roles on a Ministère de la Santé et des Services sociaux committee on lung cancer screening and Institut national d’excellence en santé et services sociaux committee on lung cancer screening. Anne Gonzalez reports a grant from Lung Cancer Canada, and is chair of the Lung Cancer Section, Thoracic Oncology, and Chest Procedures Network, American College of Chest Physicians. Scott Owen reports consulting fees for being on the advisory boards of AstraZeneca, Bristol Myers Squibb (BMS), Roche, Novocure, and Takeda. Carmela Pepe reports advisory board membership and speaker honoraria from AstraZeneca and Merck, speaker honoraria from BMS, and advisory board membership from Takeda. Jonathan Spicer reports grants to his institution from BMS, Merck, AstraZeneca, Roche, Protalix Biotherapeutics, and CLS Therapeutics, and payments from AstraZeneca, Merck, BMS, Roche, Amgen, Pfizer, Xenetic Biosciences, Protalix Biotherapeutics, BMS, and Eisai. Shirley White-Dupuis receives honoraria from the Research Institute of the McGill University Health Centre for expertise and guidance on lung health research projects as a member of Puvaqatsianirmut, and is chair of the board of directors of the Nunavik Regional Board of Health and Social Services. Larry Watt receives honoraria from the Research Institute of the McGill University Health Centre for expertise and guidance on lung health research as a member of Puvaqatsianirmut, and is also executive director of Ungava Tulattavik Health Centre. Minnie Grey is former executive director of Nunavik Regional Board and Health Social Services. Faiz Ahmad Khan reports grants from CIHR, World Health Organization, Fonds de recherche du Québec – Nature et technologies, National Research Council of Canada, and Observatoire international sur les impacts sociétaux de l’IA et du numérique, funded by the Fonds de recherche du Québec. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Introduction: Lung cancer is the most common cancer worldwide in mortality and the second in incidence. Epidemiological studies found a higher lung cancer risk for smoking women in comparison to men, but these sex differences, irrespective of smoking habits, remain controversial. One of the hypotheses concerns the genetic contribution of the sex chromosomes. However, while genome-wide association studies identified many lung cancer susceptibility loci, these analyses have excluded X-linked loci., Methods: To account for nongenetic factors, we first presented an association test based on an additive-multiplicative hazard model accounting for random/nonrandom X-inactivation process. A simulation study was performed to investigate the properties of the proposed test as compared with the Wald test from a Cox model with random X-inactivation process and the partial likelihood ratio test proposed by Xu et al. accounting for nonrandom X-inactivation process. Then, we performed an X chromosome-wide association study on 9,261 individuals from the population-based cohort CARTaGENE to identify susceptibility loci for lung cancer among current and past smokers. We adjusted for the PLCOm2012 lung cancer risk score used in screening programs., Results: Simulation results show the good behavior of the proposed test in terms of power and type I error probability as compared to the Xu et al. and the Wald test. Using the proposed test statistic and adjusting for the PLCOm2012 score, the X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 (p = 2.75×10-9) and rs12835699 (p = 1.26×10-6). For both SNPs, the minor allele was associated with lower lung cancer risk. Adjusting for multiple testing, no signal was detected using the Wald or the Xu et al. likelihood ratio tests., Conclusion: By taking into account smoking behavior and the X-inactivation process, the investigation of the X chromosome has shed a new light on the association between X-linked loci and lung cancer. We identified two loci associated with lung cancer located in the IL1RAPL1 gene. This finding would have been overlooked by examining only results from other test statistics., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

Background: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19., Objective: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population., Design: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424)., Setting: 12 clinical sites in Brazil., Participants: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease., Intervention: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos., Measurements: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions., Results: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected., Limitation: Low event rate overall, consistent with contemporary trials in vaccinated populations., Conclusion: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care., Primary Funding Source: Latona Foundation, FastGrants, and Rainwater Charitable Foundation., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3305.

Background: The PLCO m2012 prediction tool for risk of lung cancer has been proposed for a pilot program for lung cancer screening in Quebec, but has not been validated in this population. We sought to validate PLCO m2012 in a cohort of Quebec residents, and to determine the hypothetical performance of different screening strategies., Methods: We included smokers without a history of lung cancer from the population-based CARTaGENE cohort. To assess PLCO m2012 calibration and discrimination, we determined the ratio of expected to observed number of cases, as well as the sensitivity, specificity and positive predictive values of different risk thresholds. To assess the performance of screening strategies if applied between Jan. 1, 1998, and Dec. 31, 2015, we tested different thresholds of the PLCO m2012 detection of lung cancer over 6 years (1.51%, 1.70% and 2.00%), the criteria of Quebec's pilot program (for people aged 55-74 yr and 50-74 yr) and recommendations from 2021 United States and 2016 Canada guidelines. We assessed shift and serial scenarios of screening, whereby eligibility was assessed annually or every 6 years, respectively., Results: Among 11 652 participants, 176 (1.51%) lung cancers were diagnosed in 6 years. The PLCO m2012 tool underestimated the number of cases (expected-to-observed ratio 0.68, 95% confidence interval [CI] 0.59-0.79), but the discrimination was good (C-statistic 0.727, 95% CI 0.679-0.770). From a threshold of 1.51% to 2.00%, sensitivities ranged from 52.3% (95% CI 44.6%-59.8%) to 44.9% (95% CI 37.4%-52.6%), specificities ranged from 81.6% (95% CI 80.8%-82.3%) to 87.7% (95% CI 87.0%-88.3%) and positive predictive values ranged from 4.2% (95% CI 3.4%-5.1%) to 5.3% (95% CI 4.2%-6.5%). Overall, 8938 participants had sufficient data to test performance of screening strategies. If eligibility was estimated annually, Quebec pilot criteria would have detected fewer cancers than PLCO m2012 at a 2.00% threshold (48.3% v. 50.2%) for a similar number of scans per detected cancer. If eligibility was estimated every 6 years, up to 26 fewer lung cancers would have been detected; however, this scenario led to higher positive predictive values (highest for PLCO m2012 with a 2.00% threshold at 6.0%, 95% CI 4.8%-7.3%)., Interpretation: In a cohort of Quebec smokers, the PLCO m2012 risk prediction tool had good discrimination in detecting lung cancer, but it may be helpful to adjust the intercept to improve calibration. The implementation of risk prediction models in some of the provinces of Canada should be done with caution., Competing Interests: Competing interests: Nicole Ezer reports funding from the Canadian Institutes of Health Research and Rossy Cancer Network, a speaker fee from GSK, advisory board participation with GSK and receipt of study materials from COVIS Pharma. Martin Tammemägi developed the PLCOm2012 lung cancer risk prediction models (and related models), used in the current study. To date, he has not received any money for use of the model, nor does he anticipate any payments in the future. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD., Methods: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD., Results: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97)., Conclusions: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms., Competing Interests: Conflict of interest: M. Cherian reports no conflict of interest. K.M.A. Magner reports no conflict of interest. G.A. Whitmore reports no conflict of interest. K.L. Vandemheen reports no conflict of interest. C. Bergeron reports grants, contracts or honoraria from Novartis, Biohaven, AstraZeneca, Sanofi, Valeo and Grifols; and advisory board participation Sanofi, AstraZeneca, GlaxoSmithKline, Takeda and Valeo. L-P. Boulet reports grants, contracts, consulting fees or honoraria from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Regeneron, Covis and Novartis; royalties or licences from UptoDate and Taylor & Francis; leadership roles with the Global Initiative for Asthma (GINA), Global Asthma Association (INTERASMA) and Canadian Thoracic Society; and holds the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. A. Cote reports grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Valeo, Sanofi-Regeneron and Covis; and advisory board participation with AstraZeneca, Sanofi and Valeo. S.K. Field reports grants, contracts, consulting fees or honoraria from Bayer, Insmed, Merck, Valeo and GlaxoSmithKline. E. Penz reports grants, contracts, consulting fees or honoraria from the Saskatchewan Health Research Foundation, CIHR, Respiratory Research Centre, SCPOR, AstraZeneca, Saskatchewan Cancer Agency, GlaxoSmithKline, Sanofi, Genzyme, ICBEM and Boehringer Ingelheim; and leadership roles with the Canadian Thoracic Society COPD Assembly, CIHR Institute Advisory Board and Youth4Change. R.A. McIvor reports no conflict of interest. C. Lemière repots grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Sanofi and Novartis; and royalties or licences from UptoDate. S. Gupta reports no conflict of interest. I. Mayers reports no conflict of interest. M. Bhutani reports grants, contracts, consulting fees, support for travel or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Novartis, Grifols, Sanofi, Covis, Valeo, Lung Association of Saskatchewan, Canadian Thoracic Society and Lung Association of Alberta and Northwest Territories; and leadership roles with the Canadian Thoracic Society and Alberta Health Services. P. Hernandez reports grants, contracts, support for travel or honoraria from the CIHR, Cyclomedia, Boehringer Ingelheim, Vertex, Grifols, AstraZeneca, Boehringer Ingelheim, Janssen and Canadian Thoracic Society; advisory board participation with Acceleron, AstraZeneca, Boehringer Ingelheim, Covis, GlaxoSmithKline, Grifols, Janssen, Novartis, Sanofi, Takeda and Valeo; and leadership roles with the Canadian Thoracic Society. M.D. Lougheed reports grants, contracts or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Canadian Thoracic Society and MDBriefcase; advisory board participation with AstraZeneca; leadership roles with the Canadian Thoracic Society, Health Quality Ontario and the Lung Association. C.J. Licskai reports no conflict of interest. T. Azher reports no conflict of interest. M. Ainslie reports no conflict of interest. N. Ezer reports grants, contracts or honoraria from the CIHR, Rossy Cancer Network, Covis Pharma, GlaxoSmithKline, AstraZeneca, Fédération des Omnipracticiens du Québec and Médecin du Québec Magazine; advisory board participation with GlaxoSmithKline; leadership role with the Quebec Ministry of Health Lung Cancer Screening Implementation Committee; and receipt of study drug from Covis. S. Mulpuru reports no conflict of interest. S.D. Aaron reports honoraria from AstraZeneca, Sanofi and GlaxoSmithKline; and advisory board participation with AstraZeneca, GlaxoSmithKline and Sanofi., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: There is a literature gap for hospitals in single-payer health care systems quantifying the influence of hospital volume on outcomes after major lung cancer resection. We aimed to determine the effect of hospital volume on mortality and length of stay., Methods: A retrospective cohort study using administrative, population-based data from a single-payer universal health care system was performed in adults with non-small cell lung cancer who underwent lobectomy or pneumonectomy between 2008 and 2017. Hospital volume was defined as the average annual number of major lung resections performed at each institution. Length of stay and postoperative mortality were compared using multivariable linear and nonlinear regression between hospital volume categories and continuously. Adjusted association between hospital volume and postoperative mortality was determined by multivariable logistic regression., Results: In all, 10 831 lung resections were performed: 1237 pneumonectomies and 9594 lobectomies. Patients undergoing lobectomy at high-volume hospitals had shorter median length of stay (6 vs 8 days, P = .001) compared with low-volume hospitals. After adjusting for confounders, surgery at a high-volume center was significantly associated with shorter length of stay after lobectomy and overall resections (P ≤ .001), but not after pneumonectomy (P = .787). Surgery at a high-volume center was positively associated with improved 90-day mortality in lobectomy and overall procedures (odds ratio 0.607 [95% confidence interval, 0.399 to 0.925], and 0.632 [95% confidence interval, 0.441 to 0.904], respectively). Volume was not a predictor of 90-day mortality after pneumonectomy (odds ratio 0.533 [95% confidence interval, 0.257 to 1.104], P = .090)., Conclusions: Surgery at a high-volume center was positively correlated with improved 90-day survival and shorter hospital length of stay. The results support regionalized lung cancer care in a single-payer health care system., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality., Methods and Analysis: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI., Ethics and Dissemination: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: NCT04851015., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Interpretation of Low Dose CT scans and protocol driven management of findings is a key aspect of lung cancer screening program performance. Reliable and reproducible methods are needed to communicate radiologists' interpretation to the screening program or clinicians driving management decision., Methods: We performed an audit of a subset of dictated reports from the PANCAN study to assess for omissions. We developed an electronic synoptic reporting tool for radiologists embedded in a clinical documentation system software. The tool was then used for reporting as part of the Alberta Lung Cancer Screening Study and McGill University Health Centre Pilot Lung Cancer Screening Program., Results: Fifty reports were audited for completeness. At least one omission was noted in 30 (70%) of reports, with a major omission (missing lobe, size, type of nodule in report or actionable incidental finding in recommendation section of report) in 24 (48%). Details of the reporting template and functionality such as automated nodule cancer risk assessment, Lung-RADS category assignment, auto-generated narrative type report as well as personalize participant results letter is provided. A description of the system's performance in its application in 2815 CT reports is then summarized., Conclusions: We found that narrative type radiologist reports for lung cancer screening CT examinations frequently lacked specific discrete data elements required for management. We demonstrate the successful implementation of a radiology synoptic reporting system for use in lung cancer screening, and the use of this information to drive program management and communications., (© 2022. The Author(s).)

Introduction: Smoking cessation integration within lung cancer screening programs is challenging. Currently, phone counselling is available across Canada for individuals referred by healthcare workers and by self-referral. We compared quit rates after phone counselling interventions between participants who self-refer, those referred by healthcare workers, and those referred by a lung cancer screening program., Methods: This is a retrospective cohort study of participants referred to provincial smoking cessation quit line in contemporaneous cohorts: self-referred participants, healthcare worker referred, and those referred by a lung cancer screening program if they were still actively smoking at the time of first contact. Baseline, covariates (sociodemographic information, smoking history, and history of mental health disorder) and quit intentions (stage of change, readiness for change, previous use of quit programs, and previous quit attempts) were compared among the three cohorts. Our primary outcome was defined as self-reported 30-day abstinence rates at 6 months. Multivariable logistic regression was used to identify whether group assignment was associated with higher quit rates., Results: Participants referred by a lung cancer screening program had low quit rates (12%, 95% CI: 5-19) at six months despite the use of phone counselling. Compared to patients who were self-referred to the smoking cessation phone helpline, individuals referred by a lung cancer screening program were much less likely to quit (adjusted OR 0.37; 95% CI: 0.17-0.8), whereas those referred by healthcare workers were twice as likely to quit (adjusted OR 2.16 (1.3-3.58)) even after adjustment for differences in smoking intensity and quit intentions., Conclusions: Phone counselling alone has very limited benefit in a lung cancer screening program. Participants differ significantly from those who are otherwise referred by healthcare workers. This study underlines the importance of a dedicated and personalized tobacco treatment program within every lung cancer screening program. The program should incorporate best practices and encourage treatment regardless of readiness to quit., Competing Interests: NE works as a consultant for the Programme Quebecois de Cancerologie lung cancer screening demonstration project. All other authors declare that they have no conflicts of interest., (Copyright © 2022 Ankita Ghatak et al.)

Objective: To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19., Design: Randomised, double blind, placebo controlled trial., Setting: Three Canadian provinces (Quebec, Ontario, and British Columbia)., Participants: 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea., Intervention: Participants were randomised to receive either inhaled ciclesonide (600 μg twice daily) and intranasal ciclesonide (200 μg daily) or metered dose inhaler and nasal saline placebos for 14 days., Main Outcome Measures: The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex., Results: The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval -7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered., Conclusion: Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed., Trial Registration: ClinicalTrials.gov NCT04435795., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: NE reports grants from Fonds de Recherche du Québec en Santé, grants from Rossy Cancer Network, non-financial support from COVIS Pharma (study drug donation), advisory board fees from Glaxo Smith Kline, advisory board fees from Astra Zeneca, grants from Canadian Institute of Health Research, grants from MEDTEQ, outside the submitted work. SB reports personal fees from Verity Pharma and from Merck, outside the submitted work. All remaining authors declare no support from any organisation for the submitted; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Microabstract: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8). Accuracy of diagnosis can be significantly improved with integration of NGS data., Background: Distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastases (IPM) is challenging. The goal of this study was to evaluate how Next Generation Sequencing (NGS) information may be integrated in the diagnostic strategy., Patients and Methods: Patients with multiple lung adenocarcinomas were classified using both the comprehensive histologic assessment and NGS. We computed the joint probability of each pair having independent mutations by chance (thus being classified as MPLC). These probabilities were computed using the marginal mutation rates of each mutation, and the known negative dependencies between driver genes and different gene loci. With these NGS-driven data, cases were re-classified as MPLC or IPM., Results: We analyzed 61 patients with a total of 131 tumors. The most frequent mutation was KRAS (57.3%) which occured at a rate higher than expected (p < 0.001) in lung cancer. No mutation was detected in 25/131 tumors (19.1%). Discordant molecular findings between tumor sites were found in 46 patients (75.4%); 11 patients (18.0%) had concordant molecular findings, and 4 patients (6.6%) had concordant molecular findings at 2 of the 3 sites. After integration of the NGS data, the initial diagnosis was confirmed for 41 patients (67.2%), the diagnosis was revised for 12 patients (19.7%) or was considered as non-informative for 8 patients (13.1%)., Conclusion: Integrating the information of NGS data may significantly improve accuracy of diagnosis and staging., (Copyright © 2021. Published by Elsevier Ltd.)

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21-75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0-1 exacerbations in past 12 months) participated in regular exercise as much as they wanted (χ (9) 2 =20.43, Cramer's V =.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness ( p <.001, η 2 p =.86) and the most common facilitator was engaging as part of their routine ( p <.001, η 2 p =.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities.

The continuing development of avionics for Unmanned Aircraft Systems (UASs) is introducing higher levels of intelligence and autonomy both in the flight vehicle and in the ground mission control, allowing new promising operational concepts to emerge. One-to-Many (OTM) UAS operations is one such concept and its implementation will require significant advances in several areas, particularly in the field of Human-Machine Interfaces and Interactions (HMI 2 ). Measuring cognitive load during OTM operations, in particular Mental Workload (MWL), is desirable as it can relieve some of the negative effects of increased automation by providing the ability to dynamically optimize avionics HMI 2 to achieve an optimal sharing of tasks between the autonomous flight vehicles and the human operator. The novel Cognitive Human Machine System (CHMS) proposed in this paper is a Cyber-Physical Human (CPH) system that exploits the recent technological developments of affordable physiological sensors. This system focuses on physiological sensing and Artificial Intelligence (AI) techniques that can support a dynamic adaptation of the HMI 2 in response to the operators' cognitive state (including MWL), external/environmental conditions and mission success criteria. However, significant research gaps still exist, one of which relates to a universally valid method for determining MWL that can be applied to UAS operational scenarios. As such, in this paper we present results from a study on measuring MWL on five participants in an OTM UAS wildfire detection scenario, using Electroencephalogram (EEG) and eye tracking measurements. These physiological data are compared with a subjective measure and a task index collected from mission-specific data, which serves as an objective task performance measure. The results show statistically significant differences for all measures including the subjective, performance and physiological measures performed on the various mission phases. Additionally, a good correlation is found between the two physiological measurements and the task index. Fusing the physiological data and correlating with the task index gave the highest correlation coefficient (CC = 0.726 ± 0.14) across all participants. This demonstrates how fusing different physiological measurements can provide a more accurate representation of the operators' MWL, whilst also allowing for increased integrity and reliability of the system.

Lung cancer is the most frequent type of cancer-related death in people living with HIV (PLWH). We conducted a review of primary lung cancers in PLWH at the McGill University Health Centre from 1988-May 2018 to understand potential factors contributing to their development prior to the implementation of a lung cancer screening program. Twenty-seven individuals had a diagnosis of a lung tumor. Of these individuals, 21 (78%) had a primary lung cancer, over 21,428 person-years follow-up. Median age was 54.5 years [25th and 75th percentiles 49.0, 62.0]. Median CD4 count was 185.0 cells/μL [25th and 75th percentiles 54.0, 446.0] and 52% were on antitretroviral therapy with suppressed viral loads. Type of primary lung cancer included: non-small cell lung cancer ( n  = 15), small-cell lung cancer ( n  = 4) and bronchial carcinomas ( n  = 2). Metastatic disease at diagnosis was present in 11 (52%) persons. Survival was a median of 7.5 months from the time of diagnosis [25th and 75th percentiles 2.0, 9.0]. In conclusion, we observed a high proportion of lung cancers detected at very late stages of disease and with metastatic involvement. The implementation of a lung cancer screening program in 2018 should set a stage shift for earlier diagnosis and treatment.

Background: Pneumocystis jirovecii pneumonia (PJP) can be challenging to diagnose, often requiring bronchoscopy. Since most patients suspected of PJP undergo imaging, we hypothesized that the findings of these studies could help estimate the probability of disease prior to invasive testing., Methods: We created a cohort of patients who underwent bronchoscopy specifically to diagnose PJP and conducted a nested case-control study to compare the radiographic features between patients with (n = 72) and without (n = 288) pathologically proven PJP. We used multivariable logistic regression to identify radiographic features independently associated with PJP., Results: Chest x-ray findings poorly predicted the diagnosis of PJP. However, multivariable analysis of CT scan findings found that "increased interstitial markings" (OR 4.3; 95%CI 2.2-8.2), "ground glass opacities" (OR 3.3; 95%CI 1.2-9.1) and the radiologist's impression of PJP being "possible" (OR 2.0; 95%CI 1.0-4.1) or "likely" (OR 9.3; 95%CI 3.4-25.3) were independently associated with the final diagnosis (c-statistic 0.75)., Conclusions: Where there is clinical suspicion of PJP, the use of CT scan can help determine the probability of PJP. Identifying patients at low risk of PJP may enable better use of non-invasive testing to avoid bronchoscopy while higher probability patients could be prioritized.

Background: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited., Objective: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care., Methods: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients., Results: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased., Conclusions: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

This paper presents a sensor-orientated approach to on-orbit position uncertainty generation and quantification for both ground-based and space-based surveillance applications. A mathematical framework based on the least squares formulation is developed to exploit real-time navigation measurements and tracking observables to provide a sound methodology that supports separation assurance and collision avoidance among Resident Space Objects (RSO). In line with the envisioned Space Situational Awareness (SSA) evolutions, the method aims to represent the navigation and tracking errors in the form of an uncertainty volume that accurately depicts the size, shape, and orientation. Simulation case studies are then conducted to verify under which sensors performance the method meets Gaussian assumptions, with a greater view to the implications that uncertainty has on the cyber-physical architecture evolutions and Cognitive Human-Machine Systems required for Space Situational Awareness and the development of a comprehensive Space Traffic Management framework.

Intelligent automation and trusted autonomy are being introduced in aerospace cyber-physical systems to support diverse tasks including data processing, decision-making, information sharing and mission execution. Due to the increasing level of integration/collaboration between humans and automation in these tasks, the operational performance of closed-loop human-machine systems can be enhanced when the machine monitors the operator's cognitive states and adapts to them in order to maximise the effectiveness of the Human-Machine Interfaces and Interactions (HMI 2 ). Technological developments have led to neurophysiological observations becoming a reliable methodology to evaluate the human operator's states using a variety of wearable and remote sensors. The adoption of sensor networks can be seen as an evolution of this approach, as there are notable advantages if these sensors collect and exchange data in real-time, while their operation is controlled remotely and synchronised. This paper discusses recent advances in sensor networks for aerospace cyber-physical systems, focusing on Cognitive HMI 2 (CHMI 2 ) implementations. The key neurophysiological measurements used in this context and their relationship with the operator's cognitive states are discussed. Suitable data analysis techniques based on machine learning and statistical inference are also presented, as these techniques allow processing both neurophysiological and operational data to obtain accurate cognitive state estimations. Lastly, to support the development of sensor networks for CHMI 2 applications, the paper addresses the performance characterisation of various state-of-the-art sensors and the propagation of measurement uncertainties through a machine learning-based inference engine. Results show that a proper sensor selection and integration can support the implementation of effective human-machine systems for various challenging aerospace applications, including Air Traffic Management (ATM), commercial airliner Single-Pilot Operations (SIPO), one-to-many Unmanned Aircraft Systems (UAS), and space operations management., Competing Interests: The authors declare no conflict of interest.

Rationale: Video-assisted thoracoscopic surgery (VATS) and open lobectomy are both standard of care for the treatment of early-stage non-small cell lung cancer (NSCLC) because of equivalent long-term survival., Objectives: To evaluate whether the improved perioperative outcomes associated with VATS lobectomy are explained by surgeon characteristics, including case volume and specialty training., Methods: We analyzed the Surveillance, Epidemiology, and End Results-Medicare-linked registry to identify stage I-II NSCLC in patients above 65 years of age. We used a propensity score model to adjust for differences in patient characteristics undergoing VATS versus open lobectomy. Perioperative complications, extended length of stay, and perioperative mortality among patients were compared after adjustment for surgeon's volume and specialty using linear mixed models. We compared survival using a Cox model with robust standard errors., Results: We identified 9,508 patients in the registry who underwent lobectomy for early-stage NSCLC. VATS lobectomies were more commonly performed by high-volume surgeons (P < 0.001) and thoracic surgeons (P = 0.01). VATS lobectomy was associated with decreased adjusted odds of cardiovascular complications (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.47-0.90), thromboembolic complications (OR = 0.47; 95% CI = 0.38-0.58), extrapulmonary infections (OR = 0.75; 95% CI = 0.61-0.94), extended length of stay (OR = 0.47; 95% CI = 0.40-0.56), and perioperative mortality (OR = 0.33; 95% CI = 0.23-0.48) even after controlling for differences in surgeon volume and specialty. Long-term survival was equivalent for VATS and open lobectomy (hazard ratio = 0.95; 95% CI = 0.85-1.08) after controlling for patient and tumor characteristics, surgeon volume, and specialization., Conclusions: VATS lobectomy for NSCLC is associated with better postoperative outcomes, but similar long-term survival, compared with open lobectomy among older adults, even after controlling for surgeon experience.

Background: Guidelines recommend timely evaluation of patients with suspected lung cancer. We evaluated the impact of a Rapid Investigation Clinic (RIC) on timeliness of lung cancer diagnosis and treatment between February 2010 and December 2011., Methods: Investigation within the RIC was conducted by a pulmonologist and a nurse clinician. Controls were patients with lung cancer, investigated outside the RIC at the same institution during the same time period. The primary outcome was time between first contact with a local physician for suspected lung cancer (T0) and first treatment. Factors associated with the delay from T0 to first treatment were examined using multivariate analysis. Completeness of lung cancer staging according to guidelines was assessed., Results: A total of 195 patients were investigated within the RIC vs. 132 patients outside the RIC. The median delay between T0 and first treatment was 65 days (interquartile range [IQR] 46-92 days) in the RIC and 78 days (IQR 49-119 days) in the non-RIC patients (p ≤ 0.01). Time from T0 to pathological diagnosis was shorter in the RIC (median 26 days; IQR 14-42 days) vs. non-RIC patients (median 40 days; IQR 16-68 days). In multivariate analysis, investigation in the RIC was associated with a reduction in time to first treatment of 24 days (95% confidence interval [CI] 12-35 days) when adjusted for relevant confounders. Guideline-concordant investigation occurred more frequently in RIC patients, based on the quality indicators examined., Conclusions: A Rapid Investigation Clinic reduces delays to lung cancer diagnosis and treatment, and impacts quality of care.

Objectives: Prior studies have shown an anticancer effect of statins in patients with certain malignancies. However, it is unclear whether statins have a mortality benefit in lung cancer. We compared survival of patients with stage IV non-small cell lung cancer (NSCLC) receiving vs. not receiving statins prior to diagnosis., Methods: Using data from the Surveillance, Epidemiology and End Results registry linked to Medicare claims, we identified 5118 patients  >65 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of statin use with overall and lung cancer-specific survival while controlling for measured confounders., Results: Overall, 27% of patients were on statins at time of lung cancer diagnosis. Median survival in the statin group was 7 months, compared to 4 months in patients not treated with statins (p<0.001). Propensity score analyses found that statin use was associated with improvement in overall (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.73-0.79) and lung cancer-specific survival (HR: 0.77, 95% CI: 0.73-0.81), after controlling for baseline patient characteristics, cancer characteristics, staging work-up and chemotherapy use., Conclusions: Statin use is associated with improved survival among patients with stage IV NSCLC suggesting a potential anticancer effect. Further research should evaluate plausible biological mechanisms as well as test the effect of statins in prospective clinical trials., Competing Interests: All other authors are without any conflicts of interest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Limited resection has been increasingly used in older patients with stage IA lung cancer. However, the equivalency of limited resection versus lobectomy according to histology is unknown., Methods: We identified patients older than 65 years with stage IA invasive adenocarcinoma or squamous cell carcinoma ≤ 2 cm who were treated with limited resection (wedge or segmentectomy) or lobectomy in the Surveillance, Epidemiology, and End Results-Medicare database. We estimated propensity scores that predicted the use of limited resection and compared survival of patients treated with limited resection versus lobectomy. Treatments were considered equivalent if the upper 95th percentile of the hazard ratio (HR) for limited resection was ≤ 1.25., Results: Overall, 27% of 2,008 patients with adenocarcinoma and 32% of 1,139 patients with squamous cell carcinoma underwent limited resection. Survival analyses, adjusted for propensity score by using inverse probability weighting, showed that limited resection was not equivalent to lobectomy in patients with adenocarcinoma (HR, 1.21; upper 95% CI,1.34) or squamous cell carcinoma (HR, 1.21; upper 95% CI, 1.39). Although patients with adenocarcinomas treated with segmentectomy had equivalent survival rates to those treated with lobectomy (HR, 0.97; upper 95% CI, 1.07), outcomes of those treated with wedge resection (HR, 1.29; upper 95% CI, 1.42) did not. Among patients with squamous cell carcinoma, neither wedge resection (HR, 1.34; upper 95% CI, 1.53) nor segmentectomy (HR, 1.19; upper 95% CI, 1.36) were equivalent to lobectomy., Conclusion: We found generally that limited resection is not equivalent to lobectomy in older patients with invasive non-small-cell lung cancer ≤ 2 cm in size, although segmentectomy may be equivalent in patients with adenocarcinoma., (© 2015 by American Society of Clinical Oncology.)

Background: Limited resection and stereotactic body radiotherapy (SBRT) have emerged as treatment options for older patients with early-stage non-small-cell lung cancer (NSCLC), who are not good candidates for lobectomy., Methods: We used the Surveillance, Epidemiology and End Results-Medicare registry to identify patients older than 65 years with stage I to II NSCLC and negative lymph nodes treated with SBRT versus limited resection. We fitted a propensity score model predicting the use of SBRT and compared adjusted overall survival of patients treated with SBRT versus limited resection. Secondary analyses stratified the sample by type of limited resection (wedge versus segmentectomy), age (≤75 versus >75 years), and tumor size (<3 versus ≥3 cm). We also compared rates of surgical complications and SBRT-related toxicity in the two groups., Results: We identified 2243 patients of which 362 (16%) patients received SBRT. SBRT-treated patients were older, had higher comorbidity scores, and had larger tumors (p < 0.001 for all comparisons). Adjusted analyses showed no differences in survival (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.97-1.47) among patients treated with SBRT versus limited resection. Although survival of patients who underwent SBRT versus wedge resection was not different (HR, 1.22; 95% CI, 0.98-1.52), SBRT was associated with worse outcomes when compared with segmentectomy (HR, 1.55; 95% CI, 1.18-2.03). Adverse events were most often respiratory and more frequent in the patients treated with limited resection (28% versus 14%, p < 0.001)., Conclusion: SBRT is better tolerated and associated with similar survival when compared with wedge resection but not with segmentectomy in older patients with node-negative NSCLC.

The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson's and Alzheimer's diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-β-D-allopyranosyl-(1→2)]-6''-O-acetyl-β-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.