Prevalence and burden of difficult-to-treat and severe asthma in Australia: A national population survey.

BACKGROUND AND OBJECTIVE: Most evidence about difficult-to-treat and severe asthma (DTTA) comes from clinical trials and registries. We aimed to identify people with DTTA from a large nationally representative asthma population and describe their characteristics and healthcare utilization compared with people whose asthma was not 'difficult-to-treat'. METHODS: We conducted a cross-sectional survey of Australians aged ≥18 years with current asthma from large web-based survey panels. Enrolment was stratified by gender, age-group and state/territory based on national population data for people with asthma. Difficult-to-treat or severe asthma was defined by poor symptom control, exacerbations and/or oral corticosteroid/biologic use despite medium/high-dose inhaled therapy. Outcomes included exacerbations, healthcare utilization, multimorbidity, quality of life and coronavirus disease of 2019 (COVID-19)-related behaviour. Weighted data were analysed using SAS version 9.4. RESULTS: The survey was conducted in February-March 2021. The weighted sample comprised 6048 adults with current asthma (average age 47.3 ± SD 18.1 years, 59.9% female), with 1313 (21.7%) satisfying ≥1 DTTA criteria. Of these, 50.4% had very poorly controlled symptoms (Asthma Control Test ≤15), 36.2% were current smokers, and 85.4% had ≥1 additional chronic condition, most commonly anxiety/depression. More than twice as many participants with DTTA versus non-DTTA had ≥1 urgent general practitioner (GP) visit (61.4% vs. 27.5%, OR 4.8 [4.2-5.5, p < 0.0001]), or ≥1 emergency room visit (41.9% vs. 17.9%, OR 3.8 [3.3-4.4, p < 0.0001]) in the previous 12 months. CONCLUSION: Our findings emphasize the burden of uncontrolled symptoms, current smoking, multimorbidity and healthcare utilization in people with DTTA in the community, who may be under-represented in registries or clinical trials.

Azithromycin Induced Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Asthma remission is a potential treatment goal. RESEARCH QUESTION: Does adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared with placebo? STUDY DESIGN AND METHODS: This secondary analysis used data from the AMAZES clinical trial-a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids during the previous 6 months evaluated at 12 months and a 5-item Asthma Control Questionnaire score ≤ 1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (postbronchodilator FEV1 ≥ 80% or postbronchodilator FEV1 ≤ 5% decline from baseline) and complete remission (sputum eosinophil count < 3% plus the aforementioned criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. RESULTS: A total of 335 participants (41.5% male; median age, 61.01 years; quartile 1-3, 51.03-68.73) who completed the 12-month treatment period were included in the analysis. Twelve months of treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; P = .032) and clinical remission plus lung function criteria (50.8% vs 37.1%; P = .029) compared with placebo, respectively. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; P = .058). Sensitivity analyses supported these findings. Baseline factors (eg, better asthma-related quality of life, absence of oral corticosteroid burst in the previous year) predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. INTERPRETATION: Adults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Estimates of global mortality burden associated with short-term exposure to fine particulate matter (PM2·5).

BACKGROUND: The acute health effects of short-term (hours to days) exposure to fine particulate matter (PM2·5) have been well documented; however, the global mortality burden attributable to this exposure has not been estimated. We aimed to estimate the global, regional, and urban mortality burden associated with short-term exposure to PM2·5 and the spatiotemporal variations in this burden from 2000 to 2019. METHODS: We combined estimated global daily PM2·5 concentrations, annual population counts, country-level mortality rates, and epidemiologically derived exposure-response functions to estimate the mortality attributable to short-term PM2·5 exposure from 2000 to 2019, in the continental regions and in 13 189 urban centres worldwide at a spatial resolution of 0·1°â€ˆ× 0·1°. We tested the robustness of our mortality estimates with different theoretical minimum risk exposure levels, lag effects, and exposure-response functions. FINDINGS: Approximately 1 million (95% CI 690 000-1·3 million) premature deaths per year from 2000 to 2019 were attributable to short-term PM2·5 exposure, representing 2·08% (1·41-2·75) of total global deaths or 17 (11-22) premature deaths per 100 000 population. Annually, 0·23 million (0·15 million-0·30 million) deaths attributable to short-term PM2·5 exposure were in urban areas, constituting 22·74% of the total global deaths attributable to this cause and accounting for 2·30% (1·56-3·05) of total global deaths in urban areas. The sensitivity analyses showed that our worldwide estimates of mortality attributed to short-term PM2·5 exposure were robust. INTERPRETATION: Short-term exposure to PM2·5 contributes a substantial global mortality burden, particularly in Asia and Africa, as well as in global urban areas. Our results highlight the importance of mitigation strategies to reduce short-term exposure to air pollution and its adverse effects on human health. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise.

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

Mandating indoor air quality for public buildings.

If some countries lead by example, standards may increasingly become normalized.

COPD in Never-Smokers: BOLD Australia Study.

Purpose: Tobacco smoking is the major risk factor for COPD, and it is common for other risk factors in never-smokers to be overlooked. We examined the prevalence of COPD among never-smokers in Australia and identified associated risk factors. Methods: We used data from the Australia Burden of Obstructive Lung Disease (BOLD) study, a cross-section of people aged ≥40 years from six sites. Participants completed interviews and post-bronchodilator spirometry. COPD was primarily defined as an FEV1/FVC ratio <0.70 and secondarily as the ratio less than the lower limit of normal (LLN). Results: The prevalence of COPD in the 1656 never-smokers who completed the study was 10.5% (95% CI: 9.1-12.1%) [ratio

Biologics (mepolizumab and omalizumab) induced remission in severe asthma patients.

BACKGROUND: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. METHODS: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified. RESULTS: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission. CONCLUSION: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.

Revisiting Transfer Learning Method for Tuberculosis Diagnosis.

Transfer learning (TL) has been proven to be a good strategy for solving domain-specific problems in many deep learning (DL) applications. Typically, in TL, a pre-trained DL model is used as a feature extractor and the extracted features are then fed to a newly trained classifier as the model head. In this study, we propose a new ensemble approach of transfer learning that uses multiple neural network classifiers at once in the model head. We compared the classification results of the proposed ensemble approach with the direct approach of several popular models, namely VGG-16, ResNet-50, and MobileNet, on two publicly available tuberculosis datasets, i.e., Montgomery County (MC) and Shenzhen (SZ) datasets. Moreover, we also compared the results when a fully pre-trained DL model was used for feature extraction versus the cases in which the features were obtained from a middle layer of the pre-trained DL model. Several metrics derived from confusion matrix results were used, namely the accuracy (ACC), sensitivity (SNS), specificity (SPC), precision (PRC), and F1-score. We concluded that the proposed ensemble approach outperformed the direct approach. Best result was achieved by ResNet-50 when the features were extracted from a middle layer with an accuracy of 91.2698% on MC dataset.Clinical Relevance- The proposed ensemble approach could increase the detection accuracy of 7-8% for Montgomery County dataset and 4-5% for Shenzhen dataset.

mHealth application for improving treatment outcomes for patients with multidrug-resistant tuberculosis in Vietnam: an economic evaluation protocol for the V-SMART trial.

INTRODUCTION: The Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART) trial is a randomised controlled trial of using mobile health (mHealth) technologies to improve adherence to medications and management of adverse events (AEs) in people with multidrug-resistant tuberculosis (MDR-TB) undergoing treatment in Vietnam. This economic evaluation seeks to quantify the cost-effectiveness of this mHealth intervention from a healthcare provider and societal perspective. METHODS AND ANALYSIS: The V-SMART trial will recruit 902 patients treated for MDR-TB across seven participating provinces in Vietnam. Participants in both intervention and control groups will receive standard community-based therapy for MDR-TB. Participants in the intervention group will also have a purpose-designed App installed on their smartphones to report AEs to health workers and to facilitate timely management of AEs. This economic evaluation will compare the costs and health outcomes between the intervention group (mHealth) and the control group (standard of care). Costs associated with delivering the intervention and health service utilisation will be recorded, as well as patient out-of-pocket costs. The health-related quality of life (HRQoL) of study participants will be captured using the 36-Item Short Form Survey (SF-36) questionnaire and used to calculate quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) will be based on the primary outcome (proportion of patients with treatment success after 24 months) and QALYs gained. Sensitivity analysis will be conducted to test the robustness of the ICERs. A budget impact analysis will be conducted from a payer perspective to provide an estimate of the total budget required to scale-up delivery of the intervention. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the University of Sydney Human Research Ethics Committee (2019/676), the Scientific Committee of the Ministry of Science and Technology, Vietnam (08/QD-HDQL-NAFOSTED) and the Institutional Review Board of the National Lung Hospital, Vietnam (13/19/CT-HDDD). Study findings will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Respiratory Symptoms, Disease Burden, and Quality of Life in Australian Adults According to GOLD Spirometry Grades: Data from the BOLD Australia Study.

Purpose: Population data on the burden of chronic obstructive pulmonary disease (COPD) are often based on patient-reported diagnoses of COPD, emphysema or chronic bronchitis, without spirometry. We aimed to investigate the relationship between health burden, quality of life and severity of airway obstruction in Australian adults aged ≥40 years. Methods: We used data from the BOLD Australia study, which included randomly selected adults aged ≥40 years from six study sites to reflect the sociodemographic and geographic diversity of the Australian population (n = 3522). Participants with post-bronchodilator airflow limitation (ratio of forced expiratory volume in 1 second FEV1 to forced vital capacity <0.7) were grouped by GOLD spirometry grades 1-4. Quality of life was assessed with Short Form 12 (SF-12) Health Survey Questionnaire. Health burden was assessed as lost time off work or social activities, and healthcare utilization. Results: Of the study sample, 2969 participants did not have airflow limitation, 294 (8.4%) were classified as GOLD Grade 1, 212 (6.0%) as GOLD 2 and 43 (1.2%) as GOLD 3-4. Participants with higher GOLD grades had more respiratory symptoms, more comorbidities and greater burden than those with lower GOLD grades. The scores of mental and physical subscales of SF-12 were lower, indicating worse quality of life, from the no airflow limitation group to the GOLD 3-4 group (P = 0.03 and P < 0.001, respectively). Conclusion: Greater airflow limitation is associated with greater burden and poor quality of life. Interventions to prevent, or reduce the level of, airflow limitation will reduce the symptom burden and improve quality of life for patients.

Risk factors and clinical characteristics of breathlessness in Australian adults: Data from the BOLD Australia study.

BACKGROUND: Breathlessness is a common symptom related to a significant health burden. However, the association of breathlessness with clinical characteristics, especially objective pulmonary test results is scarce. We aimed to identify the characteristics independently associated with breathlessness in Australian adults. METHOD: The analysis used data from BOLD Australia, a cross-sectional study that included randomly selected adults aged ≥40 years from six sites in Australia. Clinical characteristics and spirometry results were compared for breathlessness (modified Medical Research Council [mMRC] grade ≥2). RESULTS: Among all respondents (n = 3321), 252 participants (7.6%) reported breathlessness. The main univariate associations were obesity, chronic respiratory diseases, heart diseases and being Indigenous Australians (odds ratios [ORs] = 2.78, 5.20, 3.77 and 4.38, respectively). Participants with breathlessness had lower pre-and post-bronchodilator lung function than those without. Impaired spirometry results including FVC or FEV1 below 80% predicted, or FEV1/FVC < LLN were independently associated with breathlessness (adjusted ORs = 2.66, 2.94 and 2.34, respectively). CONCLUSIONS: Breathlessness is common among Australian adults and is independently associated with obesity, chronic respiratory diseases, heart diseases, being Indigenous Australians, and impaired spirometry. Multi-disciplinary assessment and comprehensive investigation is needed in clinical practice to address the many factors associated with breathlessness in the population.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Finding and treating both tuberculosis disease and latent infection during population-wide active case finding for tuberculosis elimination.

In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among "high-risk" populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection-affecting up to a quarter of the global population -complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow's tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.

Smoking behaviour, tobacco sales and tobacco advertising at 40 'Smoke Free Hospitals' in Vietnam.

BACKGROUND: Tobacco remains the leading cause of preventable death globally. Vietnam's 2012 Law on Prevention and Control of Tobacco Harms establishes all healthcare facilities as smoke-free environments. We aimed to evaluate the implementation of these policies within health facilities across Vietnam. METHODS: A cross-sectional study was undertaken at 40 central, provincial, district and commune healthcare facilities in four provinces of Vietnam. The presence of tobacco sales, smoke-free signage, evidence of recent tobacco use and smoking behaviours by patients and staff were observed over a 1-week period at multiple locations within each facility. Adherence with national regulations was reported using descriptive statistics. RESULTS: 23 out of 40 facilities (57.5%) followed the requirements of the national smoke-free policy regarding tobacco sales, advertising and signage. Smoking was observed within health facility grounds at 26 (65%) facilities during the observation period. Indirect evidence of smoking was observed at 35 (88%) facilities. Sites where smoking was permitted (n=2) were more likely to have observed smoking behaviour (relative risk (RR) 2.16, 95% CI 1.83 to 2.56). Facilities where tobacco was sold (n=7) were more likely to have smoking behaviour observed at any of their sites (RR 1.53, 95% CI 0.93 to 2.51). CONCLUSIONS: Implementation of current smoke-free hospital regulations remains incomplete, with widespread evidence of smoking observed at three levels of the Vietnamese healthcare facilities. Further interventions are required to establish the reputation of Vietnamese healthcare facilities as smoke-free environments.

Causes of hypercapnic respiratory failure: a population-based case-control study.

OBJECTIVE: There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. METHODS: A case-control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. RESULTS: We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). CONCLUSIONS: COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

Clinical characteristics of adults with self-reported diagnosed asthma and/or COPD: data from the BOLD Australia Study.

Background: Diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the community is variable, often without spirometry. Some studies report that adults with both diagnostic labels (asthma+COPD) have worse health outcomes than those with asthma or COPD only, but data for Australian adults are limited. We investigated the relationship between clinical characteristics and self-reported diagnoses of asthma, COPD and both. Method: We used data from the BOLD Australia study, which included randomly selected adults aged ≥40 years from six study sites. The BOLD questionnaires and spirometry test were used in all sites. Participants were grouped by self-reported diagnosis. Demographic and clinical characteristics and lung function were compared between groups. Results: Of the study sample (n=3522), 336 reported asthma only, 172 reported COPD only, 77 reported asthma+COPD and 2937 reported neither. Fewer than half of participants with a COPD diagnosis (with or without asthma) had airflow limitation. Participants with asthma+COPD had more respiratory symptoms and greater airflow limitation than those with either diagnosis alone. Having asthma+COPD was independently associated with a higher probability of having clinically important breathlessness (modified Medical Research Council score ≥2) than asthma only (adjusted OR 3.44, 95% CI 1.86-6.33) or COPD only (adjusted OR 3.28, 95% CI 1.69-6.39). Airflow limitation (Global Initiative for Chronic Obstructive Lung Disease 2 or higher, using post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.7) was similar between asthma only and COPD only, but twice as prevalent in asthma+COPD (adjusted OR 2.18 and 2.58, respectively). Conclusions: Adults with diagnoses of asthma+COPD have a higher symptom and disease burden than those with diagnoses of asthma only or COPD only. These patients should receive regular comprehensive reviews because of the substantially increased burden of having both diagnoses.

Machine and Deep Learning for Tuberculosis Detection on Chest X-Rays: Systematic Literature Review.

BACKGROUND: Tuberculosis (TB) was the leading infectious cause of mortality globally prior to COVID-19 and chest radiography has an important role in the detection, and subsequent diagnosis, of patients with this disease. The conventional experts reading has substantial within- and between-observer variability, indicating poor reliability of human readers. Substantial efforts have been made in utilizing various artificial intelligence-based algorithms to address the limitations of human reading of chest radiographs for diagnosing TB. OBJECTIVE: This systematic literature review (SLR) aims to assess the performance of machine learning (ML) and deep learning (DL) in the detection of TB using chest radiography (chest x-ray [CXR]). METHODS: In conducting and reporting the SLR, we followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 309 records were identified from Scopus, PubMed, and IEEE (Institute of Electrical and Electronics Engineers) databases. We independently screened, reviewed, and assessed all available records and included 47 studies that met the inclusion criteria in this SLR. We also performed the risk of bias assessment using Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) and meta-analysis of 10 included studies that provided confusion matrix results. RESULTS: Various CXR data sets have been used in the included studies, with 2 of the most popular ones being Montgomery County (n=29) and Shenzhen (n=36) data sets. DL (n=34) was more commonly used than ML (n=7) in the included studies. Most studies used human radiologist's report as the reference standard. Support vector machine (n=5), k-nearest neighbors (n=3), and random forest (n=2) were the most popular ML approaches. Meanwhile, convolutional neural networks were the most commonly used DL techniques, with the 4 most popular applications being ResNet-50 (n=11), VGG-16 (n=8), VGG-19 (n=7), and AlexNet (n=6). Four performance metrics were popularly used, namely, accuracy (n=35), area under the curve (AUC; n=34), sensitivity (n=27), and specificity (n=23). In terms of the performance results, ML showed higher accuracy (mean ~93.71%) and sensitivity (mean ~92.55%), while on average DL models achieved better AUC (mean ~92.12%) and specificity (mean ~91.54%). Based on data from 10 studies that provided confusion matrix results, we estimated the pooled sensitivity and specificity of ML and DL methods to be 0.9857 (95% CI 0.9477-1.00) and 0.9805 (95% CI 0.9255-1.00), respectively. From the risk of bias assessment, 17 studies were regarded as having unclear risks for the reference standard aspect and 6 studies were regarded as having unclear risks for the flow and timing aspect. Only 2 included studies had built applications based on the proposed solutions. CONCLUSIONS: Findings from this SLR confirm the high potential of both ML and DL for TB detection using CXR. Future studies need to pay a close attention on 2 aspects of risk of bias, namely, the reference standard and the flow and timing aspects. TRIAL REGISTRATION: PROSPERO CRD42021277155; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=277155.

"It's like a forgotten issue sometimes ": Qualitative study of individuals living and caring for people with chronic breathlessness.

INTRODUCTION: This study aims to explore the perspectives of patients and carers with chronic breathlessness on current provision of care, care expectations, and self-management needs to develop relevant health services and resources to improve clinical outcomes. METHODS: In-depth semistructured interviews were conducted on patients living with chronic breathlessness and carers. RESULTS: Thirteen patients (cardiac, respiratory, and noncardiorespiratory) and two carers were interviewed (mean age 57 years, 47% female, median duration with breathlessness 5 years). Four main themes were identified: (1) living with breathlessness, (2) diagnosis delays, misdiagnosis, and knowledge gaps, (3) beyond curing disease: symptom relief and improving quality of life, and (4) self-management and limited support for it. CONCLUSION: Breathlessness has a high personal impact but remains a neglected condition in Australia. Patients suffer from lack of personal, community, and provider awareness, discontinuity of care, and too few clinical and self-management options.

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. METHODS: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). RESULTS: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. CONCLUSION: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

Beyond patient delay, navigating structural health system barriers to timely care and treatment in a high burden TB setting in Papua New Guinea.

Tuberculosis (TB) is a major public health issue in Papua New Guinea, with incidence rates particularly high in the South Fly District of Western Province. We present three case studies, along with additional vignettes, that were derived from interviews and focus groups carried out between July 2019 and July 2020 of people living in rural areas of the remote South Fly District depicting their challenges accessing timely TB diagnosis and care; most services within the district are only offered offshore on Daru Island. The findings detail that rather than 'patient delay' attributed to poor health seeking behaviours and inadequate knowledge of TB symptoms, many people were actively trying to navigate structural barriers hindering access to and utilisation of limited local TB services. The findings highlight a fragile and fragmented health system, a lack of attention given to primary health services, and undue financial burdens placed on people living in rural and remote areas associated with costly transportation to access functioning health services. We conclude that a person-centred and effective decentralised model of TB care as outlined in health policies is imperative for equitable access to essential health care services in Papua New Guinea.