Anne B. Chang

Description:Background: Chronic suppurative lung disease (CSLD) is an umbrella term to define the spectrum of endobronchial suppurative lung disease, including bronchiectasis and protracted bacterial bronchitis (PBB), associated with chronic wet or productive cough. Research that explores new therapeutic options in children with CSLD has been identified by clinicians and patients as one of the top research priorities. Mucolytic agents work to improve mucociliary clearance and interrupt the vicious vortex of airway infection and inflammation, hence they have potential as a therapeutic option. Objectives: To assess the effects of mucolytics for reducing exacerbations, improving quality of life and other clinical outcomes in children with CSLD (including PBB and bronchiectasis), and to assess the risk of harm due to adverse events. Search Methods: An Information Specialist searched the Cochrane Airways Trials Register to June 2022, and a review author searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 27 September 2024. Other review authors handsearched respiratory journals. Selection criteria: We included randomised controlled trials (RCTs), of both cross-over and parallel design, that compared a mucolytic with a placebo or 'no intervention' control group and included children (aged 18 years and under) with any type of CSLD (including PBB and bronchiectasis). We excluded studies with adult participants and studies in children with cystic fibrosis, empyema, pulmonary abscess or bronchopulmonary fistula. Data collection and analysis: Two authors independently reviewed titles and abstracts to assess eligibility for inclusion. The authors then assessed study quality and extracted data. They assessed the quality of the study using the Cochrane risk of bias tool (RoB 2), and used GRADE to assess the certainty of evidence. Outcomes of interest to be analysed included: i) for maintenance or stable state: rate of exacerbations, ii) for exacerbation state: time to resolution of respiratory exacerbation, iii) lung function - forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), iv) quality of life and v) adverse events. Only one study met the inclusion criteria, so we could not perform a meta-analysis. Data were continuous, so we reported outcomes as mean differences. Main Results: The sole included RCT was a cross-over study of 63 children in the total cohort, with reported data and analysis of only 52 children (26 per arm) with non-cystic fibrosis bronchiectasis. The study compared 3% hypertonic saline nebulised before chest physiotherapy with a control arm (physiotherapy alone), with each phase lasting eight weeks. Children in the hypertonic saline arm had a mean age of 9.80 (SD 2.97) years and 42.3% were male; those in the control arm had a mean age of 9.10 (SD 2.40) years and 38.4% were male. Only results of the first arm of the cross-over study were included in this review. The RCT reported a clinically important difference between the groups for our review's primary outcome: rate of respiratory exacerbations. The mean number of exacerbations per child-year was 2.50 (SD 0.64) in the intervention group and 7.80 (SD 1.05) in the control group (mean difference (MD) -5.30, 95% CI -5.77 to -4.83; 1 study, 52 participants; very low-certainty evidence). The RCT also reported that the percentage point improvement in mean % predicted FEV1 and FVC from baseline to week eight was better with hypertonic saline compared to control. Mean FEV1 improvement was 14.15% (SD 5.50) in the intervention group versus 5.04% (SD 5.55) in the control group (MD 9.11%, 95% CI 6.11 to 12.11; 1 study, 52 participants; very low-certainty evidence). While for FVC, the mean improvement was 13.77% (SD 5.73) compared with 7.54% (SD 4.90), respectively (MD 6.23%, 95% CI 3.33 to 9.13; 1 study, 52 participants; very low-certainty evidence). Quality of life measures were not used. We judged the study to have a high risk of bias due to unblinding, missing data, deviation from the intended intervention and reporting bias with measurement and selection of outcome measures. The authors reported that there were no dropouts due to adverse events. No data were available regarding quality of life. The included study assessed mucolytic use during a stable state, and we found no studies of mucolytic use during an exacerbation. We also found no studies assessing oral mucolytics, other inhaled mucolytics, use in PBB, or in settings other than hospital outpatients. We also found two ongoing studies, one using hypertonic saline and one using an oral mucolytic agent erdosteine, which will potentially be included in future updates of this review. Authors' Conclusions: This systematic review is limited to a single small study, which we judged to be at high risk of bias. It remains uncertain whether regular nebulised hypertonic saline during a stable state reduces exacerbations or improves lung function. Further multi-centre, well-designed RCTs of longer duration that investigate various mucolytics are required to answer this important clinical question.

Description:Small datasets are common in many fields due to factors such as limited data collection opportunities or privacy concerns. These datasets often contain high-dimensional features, yet present significant challenges of dimensionality, wherein the sparsity of data in high-dimensional spaces makes it difficult to extract meaningful information and less accurate predictive models are produced. In this regard, feature extraction algorithms are important in addressing these challenges by reducing dimensionality while retaining essential information. These algorithms can be classified into supervised, unsupervised, and semi-supervised methods and categorized as linear or nonlinear. To overview this critical issue, this review focuses on unsupervised feature extraction algorithms (UFEAs) due to their ability to handle high-dimensional data without relying on labelled information. From this review, eight representative UFEAs were selected: principal component analysis, classical multidimensional scaling, Kernel PCA, isometric mapping, locally linear embedding, Laplacian Eigenmaps, independent component analysis and Autoencoders. The theoretical background of these algorithms has been presented, discussing their conceptual viewpoints, such as whether they are linear or nonlinear, manifold-based, probabilistic density function-based, or neural network-based. After classifying these algorithms using these taxonomies, we thoroughly and systematically reviewed each algorithm from the perspective of their working mechanisms, providing a detailed algorithmic explanation for each UFEA. We also explored how these mechanisms contribute to an effective reduction in dimensionality, particularly in small datasets with high dimensionality. Furthermore, we compared these algorithms in terms of transformation approach, goals, parameters, and computational complexity. Finally, we evaluated each algorithm against state-of-the-art research using various datasets to assess their accuracy, highlighting which algorithm is most appropriate for specific scenarios. Overall, this review provides insights into the strengths and weaknesses of various UFEAs, offering guidance on selecting appropriate algorithms for small high-dimensional datasets.

Description:Background: Acute lower respiratory infections (ALRIs) remain the leading causes of repeated hospitalisations among young disadvantaged Australian and New Zealand First Nations and Timorese children. Severe (hospitalised) and recurrent ALRIs in the first years of life are associated with future chronic lung diseases (eg, bronchiectasis) and impaired lung function. Despite the high burden and long-term consequences of severe ALRIs, clinical, evidence-based and feasible interventions (other than vaccine programmes) that reduce ALRI hospitalisations in children are limited. This randomised controlled trial (RCT) will address this unmet need by trialling a commonly prescribed macrolide antibiotic (azithromycin) for 6-12 months. Long-term azithromycin was chosen as it reduces ALRI rates by 50% in Australian and New Zealand First Nations children with chronic suppurative lung disease or bronchiectasis. The aim of this multicentre, international, double-blind, placebo-containing RCT is to determine whether 6-12 months of weekly azithromycin administered to Australian and New Zealand First Nations and Timorese children after their hospitalisation with an ALRI reduces subsequent ALRIs compared with placebo. Our primary hypothesis is that children receiving long-term azithromycin will have fewer medically attended ALRIs over the intervention period than those receiving placebo. Methods: We will recruit 160 Australian and New Zealand First Nations and Timorese children aged <2 years to a parallel, superiority RCT across four hospitals from three countries (Australia, New Zealand and Timor-Leste). The primary outcome is the rate of medically attended ALRIs during the intervention period. The secondary outcomes are the rates and proportions of children with ALRI-related hospitalisation, chronic symptoms/signs suggestive of underlying chronic suppurative lung disease or bronchiectasis, serious adverse events, and antimicrobial resistance in the upper airways, and cost-effectiveness analyses. Background: The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Health Research (Australia), Health and Disability Ethics Committee (New Zealand) and the Institute National of Health-Research Technical Committee (Timor-Leste) approved this study. The study outcomes will be disseminated to academic and medical communities via international peer-reviewed journals and conference presentations, and findings reported to health departments and consumer-based health organisations. Background: Australia New Zealand Clinical Trial Registry ACTRN12619000456156.

Description:Addressing drug-resistant tuberculosis (DR-TB) is a priority of the tuberculosis (TB) programme. People with DR-TB frequently have worse outcomes and require more costly and complex management, compared with those with drug-sensitive TB (DS-TB). Our study examined the epidemiology of DR-TB in Sabah, Malaysia, a state with high TB burden. We aimed to identify factors associated with poor treatment outcomes. Retrospective cohort study. Data were derived from a national registry of TB patients from Sabah. Descriptive analyses were used to characterise DR-TB epidemiology, including annual trends. Multivariable logistic regression was used to identify factors associated with poor DR-TB treatment outcomes. Between 2016 and 2021, there were 29,337 registered TB patients, of whom 158 (0.54 %) had DR-TB. The proportion of people with DR-TB between 2016 and 2019 was between 0.32 % and 0.47 % of annual total TB, increasing to 0.97 % in 2021. The proportion of people with DR-TB who were cured or completed treatment (63.1 %) was lower compared with DS-TB (86.0 %). In multivariable analysis, poor DR-TB treatment outcomes (death, lost to follow-up, failed treatment, transferred out & lost) were significantly associated with non-citizen status (adjusted odds ratio [aOR] = 2.49; 95 %CI 1.23-5.13) and male sex (aOR = 2.34; 95 %CI 1.15-4.94). There was an increase in the proportion of TB that was DR-TB, coinciding with the COVID-19 pandemic in Sabah. Non-citizens and male sex were the most significant predictors of poor treatment outcomes among those with DR-TB.

Description:Despite significant global reductions in cases of pneumonia during the last 3 decades, pneumonia remains the leading cause of post-neonatal mortality in children aged <5 years. Beyond the immediate disease burden it imposes, pneumonia contributes to long-term morbidity, including lung function deficits and bronchiectasis. Viruses are the most common cause of childhood pneumonia, but bacteria also play a crucial role. However, the optimal duration of antibiotic therapy for bacterial pneumonia remains uncertain in both low- and middle-income countries and in high-income countries. Knowing the optimal duration of antibiotic therapy for pneumonia is crucial for effective antimicrobial stewardship. This is especially important as concerns mount over rising antibiotic resistance in respiratory bacterial pathogens, which increases the risk of treatment failure. Numerous studies have focused on the duration of oral antibiotics and short-term outcomes, such as clinical cure and mortality. In contrast, only one study has examined both intravenous and oral antibiotics and their impact on long-term respiratory outcomes following pneumonia hospitalisation. However, study findings may be influenced by their inclusion criteria when children unlikely to have bacterial pneumonia are included. Efforts to differentiate between bacterial and non-bacterial pneumonia continue, but a validated, accurate, and simple point-of-care diagnostic test remains elusive. Without certainty that a child has bacterial pneumonia, determining the optimal duration of antibiotic treatment is challenging. This review examines the evidence for the recommended duration of antibiotics for treating uncomplicated pneumonia in otherwise healthy children and concludes that the question of duration is unresolved.