HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Effectiveness of Acellular Pertussis Vaccine in Older Adults: Nested Matched Case-control Study.

BACKGROUND: Despite recommendations that older adults receive acellular pertussis vaccines, data on direct effectiveness in adults aged over 50 years are sparse. METHODS: A case-control study nested within an adult cohort. Cases were identified from linked pertussis notifications and each matched to 3 controls on age, sex, and cohort recruitment date. Cases and controls were invited to complete a questionnaire, with verification of vaccination status by their primary care provider. Vaccine effectiveness (VE) was estimated by conditional logistic regression, with adjustment for reported contact with children and area of residence. RESULTS: Of 1112 notified cases in the cohort, we had complete data for 333 cases and 506 controls. Among 172 PCR-diagnosed cases (mean age, 61 years), 11.2% versus 19.5% of controls had provider-verified pertussis vaccination, on average, 3.2 years earlier. Adjusted VE against PCR-diagnosed pertussis was 52% (95% CI, 15-73%), nonsignificantly higher if vaccinated within 2 years (63%; -5-87%). Adjusted VE was similar in adults born before 1950, presumed primed by natural infection (51%; -8-77%) versus those born 1950 or later who may have received whole-cell pertussis vaccine (53%; -11-80%) (P-heterogeneity = 0.9). Among 156 cases identified by single-point serology, adjusted VE was -55% (-177-13%). CONCLUSIONS: We found modest protection against PCR-confirmed pertussis among older adults (mean age, 61 years; range, 46-81 years) within 5 years after acellular vaccine. The most likely explanation for the markedly divergent VE estimate from cases identified by single-titer serology is misclassification arising from limited diagnostic specificity in our setting.

Lessons Learnt From Exercise Celestial Navigation: The Application of a Geographic Information System to Inform Legionnaires' Disease Control Activity.

Geographic information systems (GIS) have emerged in the past few decades as a technology capable of assisting in the control of infectious disease outbreaks. A Legionnaires' disease cluster investigation in May 2016 in Sydney, New South Wales (NSW), Australia, demonstrated the importance of using GIS to identify at-risk water sources in real-time for field investigation to help control any immediate environmental health risk, as well as the need for more staff trained in the use of this technology. Sydney Local Health District Public Health Unit (PHU) subsequently ran an exercise (based on this investigation) with 11 staff members from 4 PHUs across Sydney to further test staff capability to use GIS across NSW. At least 80% of exercise participants reported that the scenario progression was realistic, assigned tasks were clear, and sufficient data were provided to complete tasks. The exercise highlighted the multitude of geocoding applications and need for inter-operability of systems, as well as the need for trained staff with specific expertise in spatial analysis to help assist in outbreak control activity across NSW. Evaluation data demonstrated the need for a common GIS, regular education and training, and guidelines to support the collaborative use of GIS for infectious disease epidemiology in NSW. (Disaster Med Public Health Preparedness. 2019;13:372-374).

Weighted road density and allergic disease in children at high risk of developing asthma.

BACKGROUND: Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma. METHODS: We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis. RESULTS: Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06-1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01-1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03-1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children. CONCLUSION: Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.

An objective index of walkability for research and planning in the Sydney metropolitan region of New South Wales, Australia: an ecological study.

BACKGROUND: Walkability describes the capacity of the built environment to support walking for various purposes. This paper describes the construction and validation of two objective walkability indexes for Sydney, Australia. METHODS: Walkability indexes using residential density, intersection density, land use mix, with and without retail floor area ratio were calculated for 5,858 Sydney Census Collection Districts in a geographical information system. Associations between variables were evaluated using Spearman's rho (ρ). Internal consistency and factor structure of indexes were estimated with Cronbach's alpha and principal components analysis; convergent and predictive validity were measured using weighted kappa (κw) and by comparison with reported walking to work at the 2006 Australian Census using logistic regression. Spatial variation in walkability was assessed using choropleth maps and Moran's I. RESULTS: A three-attribute abridged Sydney Walkability Index comprising residential density, intersection density and land use mix was constructed for all Sydney as retail floor area was only available for 5.3% of Census Collection Districts. A four-attribute full index including retail floor area ratio was calculated for 263 Census Collection Districts in the Sydney Central Business District. Abridged and full walkability index scores for these 263 areas were strongly correlated (ρ=0.93) and there was good agreement between walkability quartiles (κw=0.73). Internal consistency ranged from 0.60 to 0.71, and all index variables loaded highly on a single factor. The percentage of employed persons who walked to work increased with increasing walkability: 3.0% in low income-low walkability areas versus 7.9% in low income-high walkability areas; and 2.1% in high income-low walkability areas versus 11% in high income-high walkability areas. The adjusted odds of walking to work were 1.05 (0.96-1.15), 1.58 (1.45-1.71) and 3.02 (2.76-3.30) times higher in medium, high and very high compared to low walkability areas. Associations were similar for full and abridged indexes. CONCLUSIONS: The abridged Sydney Walkability Index has predictive validity for utilitarian walking, will inform urban planning in Sydney, and will be used as an objective measure of neighbourhood walkability in a large population cohort. Abridged walkability indexes may be useful in settings where retail floor area data are unavailable.

Random property allocation: A novel geographic imputation procedure based on a complete geocoded address file.

Allocating an incomplete address to randomly selected property coordinates within a locality, known as random property allocation, has many advantages over other geoimputation techniques. We compared the performance of random property allocation to four other methods under various conditions using a simulation approach. All methods performed well for large spatial units, but random property allocation was the least prone to bias and error under volatile scenarios with small units and low prevalence. Both its coordinate based approach as well as the random process of assignment contribute to its increased accuracy and reduced bias in many scenarios. Hence it is preferable to fixed or areal geoimputation for many epidemiological and surveillance applications.

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.

Redistribution of traffic related air pollution associated with a new road tunnel.

The aim of this study was to assess the effect of a new road tunnel on the concentration and distribution of traffic-related air pollution (TRAP), specifically nitrogen dioxide (NO(2)) and particulate matter (PM), and to determine its relationship to change in traffic flow. We used continuously recorded data from four monitoring stations at nonroadside locations within the study area and three regional monitors outside the area. The four monitors in the study area were in background locations where smaller pollutant changes were expected compared with changes near the bypassed main road. We also deployed passive samplers to assess finer spatial variability in NO(2) including application of a land use regression model (LUR). The study was conducted from 2006 to 2008. Analysis of the continuously recorded data showed that the tunnel intervention did not lead to consistent reductions in NO(2) or PM over the wider study area. However, there were significant decreases in NO(2), NO(x), and PM(10) in the eastern section of the study area. Analysis of passive sampler data indicated that the greatest reductions in NO(2) concentrations occurred within 100 m of the bypassed main road. The LUR model also demonstrated that changes in NO(2) were most marked adjacent to the bypassed main road. These findings support the use of methods that highlight fine spatial variability in TRAP and demonstrate the utility of traffic interventions in reducing air pollution exposures for populations living close to main roads.

Validation of a spatiotemporal land use regression model incorporating fixed site monitors.

Land use regression (LUR) has been widely adopted as a method of describing spatial variation in air pollutants; however, traditional LUR methods are not suitable for characterizing short-term or time-variable exposures. Our aim was to develop and validate a spatiotemporal LUR model for use in epidemiological studies examining health effects attributable to time-variable air pollution exposures. A network of 42 NO(2) passive samplers was deployed for 12 two week periods over three years. A mixed effects model was tested using a combination of spatial predictors, and readings from fixed site continuous monitors, in order to predict NO(2) values for any two week period over three years in the defined study area. The final model, including terms based on traffic density at 50 and 150 m, population density within 500 m, commercial land use area within 750 m, and NO(2) concentrations at a central fixed site monitor, explained over 80% of the overall variation in NO(2) concentrations. We suggest that such a model can be used to study the association between variable air pollutant exposures and health effects in epidemiological studies.

Ophthalmologic presentation of oxidative phosphorylation diseases of childhood.

To investigate ophthalmologic manifestations in children with definitive oxidative phosphorylation disorders, a retrospective review was conducted of clinical and laboratory records of all such pediatric patients (n = 103) diagnosed and treated at one center between 1983 and 2006. All were residents of Victoria, Australia. Nystagmus or roving eye movements were the most common ophthalmologic manifestations as a presenting symptom of disease (13/20) and were the sole manifestation at presentation in 10/13 patients. Divergent strabismus was a presenting symptom in 5/20 patients and was the sole manifestation at presentation in 3/20 patients. Abnormal eye movements were noted in 6 patients and strabismus was noted in 4 patients with Leigh's or Leigh-like disease; in 9 of these 10 patients, Leigh's disease was the result of complex I deficiency. Altogether, ophthalmologic manifestations were noted at presentation in 12/35 patients with complex I deficiency. External ophthalmoplegia in conjunction with ptosis was the presenting symptom in 3/20 patients, all with Kearns-Sayers syndrome. Patients suspected of having oxidative phosphorylation disorders should be referred for ophthalmologic examination. Prospective studies are needed for a comprehensive elucidation of the ophthalmologic findings in these disorders.