Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care.

INTRODUCTION: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia's Home Medicine Review (HMR) can reduce patients' intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. METHOD AND ANALYSIS: Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants' cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. ETHICS AND DISSEMINATION: Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up. TRIAL REGISTRATION NUMBER: ACTRN12622000261718.

Effects of exposure to ambient ultrafine particles on respiratory health and systemic inflammation in children.

It is known that ultrafine particles (UFP, particles smaller than 0.1 µm) can penetrate deep into the lungs and potentially have adverse health effects. However, epidemiological data on the health effects of UFP is limited. Therefore, our objective was to test the hypothesis that exposure to UFPs is associated with respiratory health status and systemic inflammation among children aged 8 to 11 years. We conducted a cross-sectional study among 655 children (43.3% male) attending 25 primary (elementary) schools in the Brisbane Metropolitan Area, Australia. Ultrafine particle number concentration (PNC) was measured at each school and modelled at homes using Land Use Regression to derive exposure estimates. Health outcomes were respiratory symptoms and diagnoses, measured by parent-completed questionnaire, spirometric lung function, exhaled nitric oxide (FeNO), and serum C reactive protein (CRP). Exposure-response models, adjusted for potential personal and environmental confounders measured at the individual, home and school level, were fitted using Bayesian methods. PNC was not independently associated with respiratory symptoms, asthma diagnosis or spirometric lung function. However, PNC was positively associated with an increase in CRP (1.188-fold change per 1000 UFP cm-3 day/day (95% credible interval 1.077 to 1.299)) and an increase in FeNO among atopic participants (1.054 fold change per 1000 UFP cm-3 day/day (95% CrI 1.005 to 1.106)). UFPs do not affect respiratory health outcomes in children but do have systemic effects, detected here in the form of a positive association with a biomarker for systemic inflammation. This is consistent with the known propensity of UFPs to penetrate deep into the lung and circulatory system.

Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) in Brisbane, Queensland (Australia): study design and implementation.

Ultrafine particles are particles that are less than 0.1 micrometres (µm) in diameter. Due to their very small size they can penetrate deep into the lungs, and potentially cause more damage than larger particles. The Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) study is the first Australian epidemiological study to assess the health effects of ultrafine particles on children's health in general and peripheral airways in particular. The study is being conducted in Brisbane, Australia. Continuous indoor and outdoor air pollution monitoring was conducted within each of the twenty five participating school campuses to measure particulate matter, including in the ultrafine size range, and gases. Respiratory health effects were evaluated by conducting the following tests on participating children at each school: spirometry, forced oscillation technique (FOT) and multiple breath nitrogen washout test (MBNW) (to assess airway function), fraction of exhaled nitric oxide (FeNO, to assess airway inflammation), blood cotinine levels (to assess exposure to second-hand tobacco smoke), and serum C-reactive protein (CRP) levels (to measure systemic inflammation). A pilot study was conducted prior to commencing the main study to assess the feasibility and reliably of measurement of some of the clinical tests that have been proposed for the main study. Air pollutant exposure measurements were not included in the pilot study.

Respiratory health before and after the opening of a road traffic tunnel: a planned evaluation.

OBJECTIVE: The construction of a new road tunnel in Sydney, Australia, and concomitant reduction in traffic on a major road presented the opportunity to study the effects of this traffic intervention on respiratory health. METHODS: We made measurements in a cohort of residents in the year before the tunnel opened (2006) and in each of two years afterwards (2007-2008). Cohort members resided in one of four exposure zones, including a control zone. Each year, a respiratory questionnaire was administered (n = 2,978) and a panel sub-cohort (n = 380) performed spirometry once and recorded peak expiratory flow and symptoms twice daily for nine weeks. RESULTS: There was no consistent evidence of improvement in respiratory health in residents living along the bypassed main road, despite a reduction in traffic from 90,000 to 45,000 vpd. Residents living near tunnel feeder roads reported more upper respiratory symptoms in the survey but not in the panel sub-cohort. Residents living around the tunnel ventilation stack reported more upper and lower respiratory symptoms and had lower spirometric volumes after the tunnel opened. Air pollutant levels measured near the stack did not increase over the study period. CONCLUSION: The finding of adverse health effects among residents living around the stack is unexpected and difficult to explain, but might be due to unmeasured pollutants or risk factors or an unrecognized pollutant source nearby. The lack of improvement in respiratory health among people living along the bypassed main road probably reflects a minimal change in exposure due to distance of residence from the road.

A randomised cross-over cohort study of exposure to emissions from a road tunnel ventilation stack.

BACKGROUND AND OBJECTIVE: Road tunnels are increasingly important components of urban infrastructure. However, knowledge of their health impact on surrounding communities is limited. Our objective was to estimate the short-term respiratory health effects of exposure to emissions from a road tunnel ventilation stack. METHODS: We conducted a randomised cross-over cohort study in 36 volunteers who underwent three exposure scenarios in 2006 before the road tunnel opened, and in 2007 (n=27) and 2008 (n=20) after the tunnel opened. Exposure downwind of the stack was compared to upwind of the stack and to a distant heavily trafficked location adjacent to a main road. Spirometry, exhaled nitric oxide (eNO) and symptom scores were measured repeatedly during each 2 h exposure session. RESULTS: Downwind locations were associated with increased reports of 'dry nose' (score difference 0.36; 95% CI 0.09 to 0.63) compared with the control location (2006 vs 2007/2008), but not with impaired lung function, increased airway inflammation or other symptoms. The heavily trafficked location was associated with significantly increased eNO (ratio=1.09; 95% CI 1.04 to 1.14), eye (score difference 0.05; 95% CI 0.01 to 0.10) and chest (score difference 0.21; 95% CI 0.09 to 0.33) symptoms compared to the stack locations. CONCLUSIONS: There was no consistent evidence of adverse respiratory effects from short-term exposures downwind of the tunnel ventilation stack, except for dry nose symptoms. However, the findings of increased airway inflammation and symptoms in subjects after only 2 h exposure at the heavily trafficked location, are suggestive of detrimental effects of short-term exposures to traffic-related air pollution.

Respiratory health effects of exposure to low-NOx unflued gas heaters in the classroom: a double-blind, cluster-randomized, crossover study.

BACKGROUND: There are long-standing concerns about adverse effects of gas appliances on respiratory health. However, the potential adverse effect of low-NOx (nitrogen oxide) unflued gas heaters on children's health has not been assessed. OBJECTIVES: Our goal was to compare the respiratory health effects and air quality consequences of exposure to low-NOx unflued gas heaters with exposure to non-indoor-air-emitting flued gas heaters in school classrooms. METHODS: We conducted a double-blind, cluster-randomized, crossover study in 400 primary school students attending 22 schools in New South Wales, Australia. Children measured their lung function and recorded symptoms and medication use twice daily. Nitrogen dioxide (NO2) and formaldehyde concentrations were measured in classrooms using passive diffusion badges. RESULTS: NO2 concentrations were, on average, 1.8 times higher [95% confidence interval (CI), 1.6-2.1] and formaldehyde concentrations were, on average, 9.4 ppb higher (95% CI, 5.7-13.1) during exposure to unflued gas versus flued gas heaters. Exposure to the unflued gas heaters was associated with increased cough reported in the evening [odds ratio (OR) = 1.16; 95% CI, 1.01-1.34] and wheeze reported in the morning (OR = 1.38; 95% CI, 1.04-1.83). The association with wheeze was greater in atopic subjects. There was no evidence of an adverse effect on lung function. CONCLUSIONS: We conclude that classroom exposure to low-NOx unflued gas heaters causes increased respiratory symptoms, particularly in atopic children, but is not associated with significant decrements in lung function. It is important to seek alternative sources of heating that do not have adverse effects on health.