Relative risks of childhood developmental vulnerabilities in three Australian communities with exposure to per- and polyfluoroalkyl substances: data linkage study.

Background: Aqueous film forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS) caused local environmental contamination in three Australian residential areas: Katherine in the Northern Territory (NT), Oakey in Queensland (Qld) and Williamtown in New South Wales (NSW). We examined whether children who lived in these areas had higher risks of developmental vulnerabilities than children who lived in comparison areas without known contamination. Methods: All children identified in the Medicare Enrolment File-a consumer directory for Australia's universal healthcare insurance scheme-who ever lived in exposure areas, and a sample of children who ever lived in selected comparison areas, were linked to the Australian Early Development Census (AEDC). The AEDC data were available from four cycles: 2009, 2012, 2015 and 2018. For each exposure area, we estimated relative risks (RRs) of developmental vulnerability on each of five AEDC domains and a summary measure, adjusting for sociodemographic characteristics and other potential confounders. Findings: We included 2,429 children from the NT, 2,592 from Qld and 510 from NSW. We observed lower risk of developmental vulnerability in the Communication skills and general knowledge domain in Katherine (RR = 0.74, 95% confidence interval (CI) 0.57 to 0.97), and higher risks of developmental vulnerability in the same domain (RR = 1.49, 95% CI 1.18 to 1.87) and in the Physical health and wellbeing domain in Oakey (RR = 1.31, 95% CI 1.06 to 1.61). Risks of developmental vulnerabilities on other domains were not different from those in the relevant comparison areas or were uncertain due to small numbers of events. Conclusion: There was inadequate evidence for increased risks of developmental vulnerabilities in children who ever lived in three PFAS-affected areas in Australia.

Relative Risks of Adverse Perinatal Outcomes in Three Australian Communities Exposed to Per- and Polyfluoroalkyl Substances: Data Linkage Study.

INTRODUCTION: Firefighting foams containing per- and polyfluoroalkyl substances (PFAS) have caused environmental contamination in several Australian residential areas, including Katherine in the Northern Territory (NT), Oakey in Queensland (Qld), and Williamtown in New South Wales (NSW). We examined whether the risks of adverse perinatal outcomes were higher in mothers living in these exposure areas than in selected comparison areas without known contamination. METHODS: We linked residential addresses in exposure areas to addresses collected in the jurisdictional Perinatal Data Collections of the NT (1986-2017), Qld (2007-2018), and NSW (1994-2018) to select all pregnancies from mothers who gave birth while living in these areas. We also identified one comparison group for each exposure area by selecting pregnancies where the maternal address was in selected comparison areas. We examined 12 binary perinatal outcomes and three growth measurements. For each exposure area, we estimated relative risks (RRs) of adverse outcomes and differences in means of growth measures, adjusting for sociodemographic characteristics and other potential confounders. RESULTS: We included 16,970 pregnancies from the NT, 4654 from Qld, and 7475 from NSW. We observed elevated risks of stillbirth in Oakey (RR = 2.59, 95% confidence interval (CI) 1.25 to 5.39) and of postpartum haemorrhage (RR = 1.94, 95% CI 1.13 to 3.33) and pregnancy-induced hypertension (RR = 1.88, 95% CI 1.30 to 2.73) in Williamtown. The risks of other perinatal outcomes were not materially different from those in the relevant comparison areas or were uncertain due to small numbers of events. CONCLUSIONS: There was limited evidence for increased risks of adverse perinatal outcomes in mothers living in areas with PFAS contamination from firefighting foams. We found higher risks of some outcomes in individual areas, but these were not consistent across all areas under study and could have been due to chance, bias, or confounding.

Economic evaluations of whole-genome sequencing for pathogen identification in public health surveillance and health-care-associated infections: a systematic review.

Whole-genome sequencing (WGS) has resulted in improvements to pathogen characterisation for the rapid investigation and management of disease outbreaks and surveillance. We conducted a systematic review to synthesise the economic evidence of WGS implementation for pathogen identification and surveillance. Of the 2285 unique publications identified through online database searches, 19 studies met the inclusion criteria. The economic evidence to support the broader application of WGS as a front-line pathogen characterisation and surveillance tool is insufficient and of low quality. WGS has been evaluated in various clinical settings, but these evaluations are predominantly investigations of a single pathogen. There are also considerable variations in the evaluation approach. Economic evaluations of costs, effectiveness, and cost-effectiveness are needed to support the implementation of WGS in public health settings.

Psychological distress in three Australian communities living with environmental per- and polyfluoroalkyl substances contamination.

BACKGROUND: Environmental chemical contamination is a recognised risk factor for psychological distress, but has been seldom studied in the context of per- and polyfluoroalkyl substances (PFAS) contamination. We examined psychological distress in a cross-sectional study of three Australian communities exposed to PFAS from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities without environmental contamination. METHODS: Participation was voluntary following recruitment from a PFAS blood-testing program (exposed) or random selection (comparison). Participants provided blood samples and completed a survey on their exposure history, sociodemographic characteristics, and four measures of psychological distress (Kessler-6, Distress Questionnaire-5, Patient Health Questionnaire-15, and Generalised Anxiety Disorder-7). We estimated prevalence ratios (PR) of clinically-significant psychological distress scores, and differences in mean scores: (1) between exposed and comparison communities; (2) per doubling in PFAS serum concentrations in exposed communities; (3) for factors that affect the perceived risk of living in a community exposed to PFAS; and (4) in relation to self-reported health concerns. RESULTS: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher levels of self-reported psychological distress in exposed communities than in comparison communities (e.g., Katherine compared to Alice Springs, Northern Territory: clinically-significant anxiety scores, adjusted PR = 2.82, 95 % CI 1.16-6.89). We found little evidence to suggest that psychological distress was associated with PFAS serum concentrations (e.g., Katherine, PFOS and anxiety, adjusted PR = 0.85, 95 % CI 0.65-1.10). Psychological distress was higher among exposed participants who were occupationally exposed to firefighting foam, used bore water on their properties, or were concerned about their health. CONCLUSION: Psychological distress was substantially more prevalent in exposed communities than in comparison communities. Our findings suggest that the perception of risks to health, rather than PFAS exposure, contribute to psychological distress in communities with PFAS contamination.

Liver and cardiometabolic markers and conditions in a cross-sectional study of three Australian communities living with environmental per- and polyfluoroalkyl substances contamination.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive. OBJECTIVES: We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities. METHODS: Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression). RESULTS: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease. DISCUSSION: Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference.

Longitudinal measurements of per- and poly-fluoroalkyl substances (PFAS) in archived human serum samples between 1975 and 1995 in Australia.

Per- and poly-fluoroalkyl substances (PFAS) are a group of manmade compounds produced since the 1950 s and used in a range of industrial processes and consumer products. In Australia, PFAS serum concentrations have been measured in the general population since 2002. However, few studies have retrospectively measured PFAS concentrations in serum samples representative of a general population prior to 2000, none of which have been conducted in Australia. To understand the general population's exposure to PFAS prior to 2002, longitudinal PFAS serum concentration measurements are required. In the current study, we accessed 'The Busselton Health Study Data Bank' to analyse archived serum samples for PFAS. Repeat serum samples collected in 1975, 1981 and 1995 were obtained from 17 participants. Of the 35 PFAS analysed, 13 PFAS were detected in the serum samples collected in 1975. Both the detection frequency and ∑PFAS serum concentrations increased between 1975 and 1995. Median ∑PFAS serum concentration increased over 7-fold; from 3.3 ng/mL in 1975-26 ng/mL in 1995. The increase in serum concentrations reflects the global production history of these PFAS during this period in time.

Associations between serum perfluoroalkyl acid (PFAA) concentrations and health related biomarkers in firefighters.

OBJECTIVES: Firefighters who used aqueous film forming foam in the past have experienced elevated exposures to perfluoroalkyl acids (PFAAs). The objective of this study was to examine the associations between clinical chemistry endpoints and serum concentrations of perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorooctane sulfonate (PFOS) in firefighters. Multiple linear regression was used to assess relationships between PFAA serum concentrations and biochemical markers for cardiovascular disease, kidney-, liver- and thyroid function, in a cross-sectional survey of 783 firefighters with elevated levels of PFHxS, PFHpS and PFOS in relation to the most recently reported levels in the general Australian population. Linear logistic regression was used to assess the odds ratios for selected self-reported health outcomes. Repeated measures linear mixed models were further used to assess relationships between PFAAs and biomarkers for cardiovascular disease and kidney function longitudinally in a subset of the firefighters (n = 130) where serum measurements were available from two timepoints, five years apart. In the cross-sectional analysis, higher levels of all PFAAs were significantly associated with higher levels of biomarkers for cardiovascular disease (total-cholesterol, and LDL-cholesterol). For example, doubling in PFOS serum concentration were associated with increases in total cholesterol (ß:0.111, 95% confidence interval (95%CI): 0.026, 0.195 mmol/L) and LDL-cholesterol (ß: 0.104, 95%CI:0.03, 0.178 mmol/L). Doubling in PFOA concentration, despite not being elevated in the study population, were additionally positively associated with kidney function marker urate (e.g., ß: 0.010, 95%CI; 0.004, 0.016 mmol/L) and thyroid function marker TSH (e.g., ß: 0.087, 95%CI: 0.014, 0.161 mIU/L). PFAAs were not associated with any assessed self-reported health conditions. No significant relationships were observed in the longitudinal analysis. Findings support previous studies, particularly on the association between PFAAs and serum lipids.

Biomonitoring of per- and polyfluoroalkyl substances (PFAS) exposure in firefighters: Study design and lessons learned from stakeholder and participant engagement.

Firefighters may be occupationally exposed to per- and polyfluoroalkyl substances (PFASs) through Aqueous Film-Forming Foam (AFFF), smoke, dust and turnout gear, in addition to other background exposure sources. Epidemiological assessment of PFAS exposure in an occupational cohort of firefighting staff commenced in 2013-2014, following cessation of PFAS-based AFFF in Australian aviation. Here we present the study design and methodology of a follow-up study conducted in 2018-2019. We focus on our experiences engaging with stakeholders and participants with the establishment of an inclusive study group and highlight the key lessons learned from implementing a co-design process in the study. The study included a cross-sectional assessment of blood serum concentrations of 40 PFASs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS), and 14 health-related biomarkers in 799 current and former Aviation Rescue Firefighting Services employees. A large proportion (87%) of the participants from the preliminary exposure study in 2013-2014 were re-recruited in the follow-up study. This enabled further longitudinal analyses in this subset of 130 participants. Participants included employees from different work roles and timeframes, reflecting the periods when three different firefighting foams were utilised in Australia. Establishment of a collaborative and inclusive study group (including stakeholders and participants) contributed to several components of the study design, including the expansion of robust analytical quality assurance and control measurements, and tailoring of communication and dissemination strategies. These outcomes were key factors that improved transparency of the research design, methods and results. Additionally, implementing elements of co-design helped build trust between researchers and participants, which is an important consideration for studies funded by stakeholders related to the exposure source.

Health and social concerns about living in three communities affected by per- and polyfluoroalkyl substances (PFAS): A qualitative study in Australia.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS) is a public health issue globally. In Australia high concentrations of PFAS have been found in environments close to sites where Aqueous Film Forming Foams (AFFF) were historically used for firefighting activities. This has resulted in significant community concern about the potential long-term health effects of these chemicals. OBJECTIVE: We describe residents' perceptions and experiences of PFAS in three regional Australian towns where exposure has occurred. METHODS: We conducted focus groups to generate free-flowing open discussion on PFAS in three affected communities, including some with significant numbers of First Nations Peoples. We recruited participants using a range of media outlets and postal services. Focus group transcripts were analysed thematically to identify major shared concerns using Atlas Ti. RESULTS: One hundred and eighty residents attended fifteen focus groups that were conducted in the three communities. They included 69 First Nations People living in three communities near the town of Katherine in the Northern Territory. Study participants were concerned about potential physical health effects of exposure to PFAS, such as cancer clusters, unexplained deaths, potential exacerbation of existing health conditions, and the future health of their children. They expressed feelings of stress and anxiety about living with uncertainty related to the possible health and the socio-economic impacts of PFAS contamination in their communities. CONCLUSION: While research has concentrated on the physical health effects of PFAS, more attention needs to be given to the immediate psychosocial impacts of living in an affected community.

Investigating spatial convergence of diagnosed dementia, depression and type 2 diabetes prevalence in West Adelaide, Australia.

BACKGROUND: Comorbid depression and type 2 diabetes (T2D) is an important risk factor for dementia. This study investigates the factors associated with, the spatial variation and spatial convergence of diagnosed cases of these conditions. This approach may identify areas with unmet needs. METHODS: We used cross-sectional data (2010 to 2014) from 16 general practices in west Adelaide, Australia. Multi-level modelling accounting for individual-level characteristics nested within statistical area level 1 (SA1) determined covariate associations with these three diseases. Getis-Ord Gi method was used to investigate spatial variation, hot spots and cold spots of these conditions. RESULTS: 1.4% of active patients in west Adelaide aged 45 and above were diagnosed with dementia, 9.6% with depression and 13.3% with T2D. Comorbidity was significant across all three diseases. Elderly age (65+ years) was significantly associated with diagnosed dementia and T2D. Hyperlipidemia or hypertension diagnosis and belonging to lower socioeconomic status were significantly associated with diagnosed T2D and depression. The spatial distribution of each disease varied across west Adelaide. Spatial convergence of the three diseases was observed in two large hot spot clusters and one main cluster of cold spots. LIMITATIONS: Due to underreporting, potentially significant covariates like alcohol intake were unable to be assessed. There may be a bias towards health-conscious individuals or patients managing diagnosed diseases that actively visit their general practice. CONCLUSIONS: Patterns of spatial convergence and the shared associations in dementia, depression and diabetes enable policymakers to tailor interventions to the areas where risk of these conditions are greater.

Using Geographical Convergence of Obesity, Cardiovascular Disease, and Type 2 Diabetes at the Neighborhood Level to Inform Policy and Practice.

INTRODUCTION: Chronic diseases are increasing across the world. Examination of local geographic variation in chronic disease patterns can enable policy makers to identify inequalities in health outcomes and tailor effective interventions to communities at higher risk. Our study aimed to determine the geographic variation of obesity, cardiovascular disease (CVD), and type 2 diabetes, using general practice clinical data. Further objectives included identifying regions of significantly high and low clusters of these conditions and assessing their association with sociodemographic characteristics. METHODS: A cross-sectional approach was used to determine the prevalence of obesity, CVD, and type 2 diabetes in western Adelaide, Australia. The Getis-Ord Gi* method was used to identify significant hot spots of the conditions. Additionally, we used the Pearson correlation test to determine the association between disease clusters and risk factors, including socioeconomic status (SES), smoking history, and alcohol consumption. RESULTS: The spatial distribution of obesity, CVD, and type 2 diabetes varied across communities. Hot spots of these conditions converged in 3 locations across western Adelaide. An inverse relationship was observed between area-level prevalence of CVD, obesity, and type 2 diabetes with SES. CONCLUSION: Identification of significant disease clusters can help policy makers to target prevention strategies at the right people, in the right location. The approach taken in our study can be applied to identify clusters of other chronic diseases across the world, wherever researchers have access to clinical data.