Homelessness, psychiatric disorders, and violence in Denmark: a population-based cohort study.

BACKGROUND: Homelessness is associated with adverse health and social outcomes. People experiencing homelessness have been found to have a high risk of violent crime victimisation as well as high prevalence of psychiatric disorders. It is poorly understood whether experiencing homelessness is associated with additional risks of violent offending and whether psychiatric disorders contribute to these risks. We examined the association between homelessness, psychiatric disorders, and first violence offence leading to conviction. METHODS: We did a nationwide, register-based cohort study of all Danish residents who were alive at least 1 day during the study period, born between Jan 1, 1980, and Dec 31, 2006, and aged 15 years or older retrieved from the Danish Civil Registration System, which was linked to registers with information on homelessness, health care, and criminality. The exposure was any experience of homelessness, which was defined as having at least one contact with a homeless shelter during the study period. The outcome was first violent offence leading to a conviction. We calculated incidence rates per 10 000 person-years, incidence rate ratios (IRRs) using Poisson regression analysis, and probability of conviction of a violent offence using an Aalen-Johansen estimator. Analyses were stratified by sex and adjusted for calendar year of the study period, age, other sociodemographic factors, and psychiatric disorders. FINDINGS: The study cohort included 1 786 433 Danish residents aged 15-42 years living in Denmark at some point from Jan 1, 2001, to Dec 31, 2021, contributing to 21 336 322 person-years at risk, of whom 57 084 (3·2%) individuals had their first violent offence leading to conviction during follow-up. 10 years after their first contact with a homeless shelter, 22·9% (95% CI 21·6-24·2) of men and 7·7% (6·8-8·7) of women had committed at least one violent crime leading to conviction. The fully adjusted IRRs of a violent offence leading to conviction were 4·8 (4·5-5·1) in men and 6·3 (5·6-7·2) in women experiencing homelessness compared with individuals who had not experienced homelessness. The IRR for a violent offence leading to conviction was highest in individuals experiencing homelessness and having co-occurring psychiatric disorders compared with those not experiencing homelessness and without co-occurring psychiatric disorders, especially drug use disorders (IRR in those experiencing homelessness and having a drug use disorder: 15·3 [14·1-16·7] in men and 40·1 [33·9-47·5] in women compared with individuals not experiencing homelessness and having no drug use disorder). INTERPRETATION: Individuals experiencing homelessness had higher risks of a violent offence leading to conviction than those who had not experienced homelessness. In addition to preventing homelessness, public health and policy should consider how to reduce the risk of adverse outcomes in people experiencing homelessness. FUNDING: Lundbeck Foundation.

Partitioning of PFAS to serum, tissues, eggs, and hatchlings of an Australian freshwater turtle.

Turtles are a potential sentinel species of aquatic ecosystem health as they inhabit aquatic ecosystems, are long lived, and potentially have high exposure to anthropogenic chemicals via food and water. This study investigated per- and polyfluoroalkyl substances (PFAS) tissue partitioning in female Emydura macquarii macquarii turtle, and the maternal offloading of (PFAS) into eggs and then hatchlings as well as the accumulation of PFAS in male and female Emydura macquarii macquarii serum. Significantly higher levels of perfluorosulfonic acids (PFSAs) and perfluorocarboxylic acids (PFCAs) were measured in the male serum compared to the female turtle serum, whereas perfluoroalkane sulfonamides (FASAs) were significantly higher in the female turtle serum. Perfluorooctane sulfonate (PFOS) was the predominant PFAS in the turtles whereas PFHxA was the predominant PFAS found in the surrounding water. PFHxA was not reported in any turtle tissue or the serum. The short-chain PFSAs and FASAs appeared to be highly associated with blood; long-chain PFSAs and PFCAs were more likely to be associated with tissue. Half of the PFHxS and all the long-chain PFSAs and PFCAs reported in the yolks were transferred into the hatchlings (by mass), suggesting a potential intergenerational effect.

Metabolic disruptions and impaired reproductive fitness in wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated per- and polyfluoroalkyl substances (PFAS).

Per- and poly-fluoroalkyl substances (PFAS) pose a threat to organisms and ecosystems due to their persistent nature. Ecotoxicology endpoints used in regulatory guidelines may not reflect multiple, low-level but persistent stressors. This study examines the biological effects of PFAS on Eastern short-necked turtles in Queensland, Australia. In this study, blood samples were collected and analysed for PFAS, hormone levels, and functional omics endpoints. High levels of PFAS were found in turtles at the impacted site, with PFOS being the dominant constituent. The PFAS profiles of males and females differed, with males having higher PFAS concentrations. Hormone concentrations differed between impacted and reference sites in male turtles, with elevated testosterone and corticosterone indicative of stress. Further, energy utilisation, nucleotide synthesis, nitrogen metabolism, and amino acid synthesis were altered in both male and female turtles from PFAS-impacted sites. Both sexes show similar metabolic responses to environmental stressors from the PFAS-contaminated site, which may adversely affect their reproductive fitness. Purine metabolism, caffeine metabolism, and ferroptosis pathway changes in turtles can cause gout, cell death, and overall health problems. Further, the study showed that prolonged exposure to elevated PFAS levels in the wild could compromise turtle reproductive fitness by disrupting reproductive steroids and metabolic pathways.

The bidirectional association between psychiatric disorders and sheltered homelessness.

BACKGROUND: Psychiatric disorders and homelessness are related, but temporal associations are unclear. We aimed to explore the overlap between hospital-based psychiatric disorders and sheltered homelessness. METHODS: This population-based cohort study was conducted using the Danish registers e.g., the Danish Homeless Register and the Danish National Patient Register. The study cohort included all individuals aged 15 years or older, living in Denmark at least one day during 2002-2021 (born 1984-2006). First psychiatric diagnosis was used to define psychiatric disorder and first homeless shelter contact to define homelessness. Adjusted incidence rate ratios (IRRs) and cumulative incidences were estimated. RESULTS: Among 1 530 325 individuals accounting for 16 787 562 person-years at risk aged 15-38 years, 11 433 (0.8%) had at least one homeless shelter contact. Among 1 406 410 individuals accounting for 14 131 060 person-years at risk, 210 730 had at least one psychiatric disorder. People with any psychiatric disorder had increased risk of sheltered homelessness relative to individuals with no psychiatric disorder [IRR 9.2, 95% confidence interval (CI) 8.8-9.6]. Ten years after first psychiatric disorder, 3.0% (95% CI 2.9-3.1) had at least one homeless shelter contact. Individuals experiencing homelessness had increased risk of any psychiatric disorder compared to individuals with no homeless shelter contact (IRR 7.0, 95% CI 6.7-7.4). Ten years after first homeless shelter contact, 47.1% (45.3-48.0) had received a hospital-based psychiatric diagnosis. CONCLUSION: Strong bidirectional associations between psychiatric disorders and homelessness were identified. Health and social care professionals should be aware of and address these high risks of accumulated psychiatric and social problems.

Risk of homelessness after prison release and recidivism in Denmark: a nationwide, register-based cohort study.

BACKGROUND: Transitional periods between and across services have been linked to homelessness. We aimed to investigate the association of previous history of homelessness and psychiatric disorders with risk of homelessness after release from prison. Additionally, we examined the association between homelessness after release and risk of recidivism. METHODS: We did a nationwide, register-based cohort study of people aged 15 years or older who were released from prison for the first time in Denmark between Jan 1, 2001, and Dec 31, 2021. We obtained data using the Danish Civil Registration System with data linked across other registries (the Danish Central Criminal Register, the Danish Homeless Register, the Danish National Patient Register, and the Danish Psychiatric Central Research Register) on release date, homeless shelter contacts, psychiatric disorders, and new convictions. Outcomes were homelessness after release from prison, defined as first homeless shelter contact following release from first imprisonment, and recidivism within 2 years of release, defined as the first police-recorded criminal conviction after prison release. We calculated incidence rates per 1000 person-years, incidence rate ratios (IRRs) using Poisson regression analysis, and probability of homelessness and recidivism after release. Sex, age, calendar year, country of origin, highest educational level, relationship status, and length of index imprisonment were included as confounders. FINDINGS: The study cohort included 37 382 individuals (34 792 males [93·1%] and 2590 females [6·9%]) aged 15-41 years, who were released from prison between Jan 1, 2001, and Dec 31, 2021, contributing 202 197 person-years at risk. Mean follow-up duration was 5·4 person-years (SD 5·6). Overall, 1843 (4·9%) of 37 382 individuals became homeless. 1 year after release from prison, 788 (2·1%) of 37 382 individuals had at least one homeless shelter contact, and among 1761 individuals with previous history of homelessness before index imprisonment, 357 (20·7%) became homeless. The incidence of homelessness after release was 102·5 cases per 1000 person-years for individuals with previous history of homelessness and 6·7 cases per 1000 person-years in individuals without (IRR 16·4, 95% CI 14·8-18·2; adjusted for sex, age, and calendar year). Individuals who additionally had a mental illness had a higher risk of homelessness (IRR 22·6, 19·7-25·9) compared with those without either previous homelessness or mental illness, and a substantially higher risk was observed for those with previous homelessness and drug use disorder (25·0, 21·6-28·9) compared with those without. Within 2 years of release from prison, the probability of recidivism was 73·2% (95% CI 72·8-73·7). The risk of recidivism was higher among people experiencing homelessness after release from prison than those who did not experience homelessness after release (IRR 1·5, 95% CI 1·3-1·7), adjusted for sex, age, and calendar year. INTERPRETATION: Criminal justice services should review approaches to reduce risk of homelessness, and consider improving liaison with mental health and substance misuse services to prevent adverse outcomes on release from prison. Clinical guidelines applied to criminal justice settings should address the health of individuals who experience homelessness. FUNDING: Lundbeck Foundation.

Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater.

The leaching of per- and polyfluoroalkyl substances (PFASs) from Australian firefighting training grounds has resulted in extensive contamination of groundwater and nearby farmlands. Humans, farm animals, and wildlife in these areas may have been exposed to complex mixtures of PFASs from aqueous film-forming foams (AFFFs). This study aimed to identify PFAS classes in pooled whole blood (n = 4) and serum (n = 4) from cattle exposed to AFFF-impacted groundwater and potentially discover new PFASs in blood. Thirty PFASs were identified at various levels of confidence (levels 1a-5a), including three novel compounds: (i) perfluorohexanesulfonamido 2-hydroxypropanoic acid (FHxSA-HOPrA), (ii) methyl((perfluorohexyl)sulfonyl)sulfuramidous acid, and (iii) methyl((perfluorooctyl)sulfonyl)sulfuramidous acid, belonging to two different classes. Biotransformation intermediate, perfluorohexanesulfonamido propanoic acid (FHxSA-PrA), hitherto unreported in biological samples, was detected in both whole blood and serum. Furthermore, perfluoroalkyl sulfonamides, including perfluoropropane sulfonamide (FPrSA), perfluorobutane sulfonamide (FBSA), and perfluorohexane sulfonamide (FHxSA) were predominantly detected in whole blood, suggesting that these accumulate in the cell fraction of blood. The suspect screening revealed several fluoroalkyl chain-substituted PFAS. The results suggest that targeting only the major PFASs in the plasma or serum of AFFF-exposed mammals likely underestimates the toxicological risks associated with exposure. Future studies of AFFF-exposed populations should include whole-blood analysis with high-resolution mass spectrometry to understand the true extent of PFAS exposure.

Influence of vaccination on adverse health outcomes after SARS-CoV-2 infection among individuals with alcohol use disorder: a population-based study.

BACKGROUND AND AIMS: Alcohol use disorders (AUD) have not been included in the priority groups for early vaccine against SARS-CoV-2. We aimed to determine adverse outcomes after SARS-CoV-2 infection among individuals with AUD and how this is modified by vaccination. DESIGN, SETTING AND PARTICIPANTS: This was a registry-based cohort study carried out in Denmark, 27 February 2020 to 15 October 2021, comprising 2157 individuals with AUD and 237 541 without AUD who had had a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection during the study period. MEASUREMENTS: The association of AUD with the absolute and relative risk of hospitalization, intensive care and 60-day mortality after SARS-CoV-2 infection and of all-cause mortality throughout the follow-up period were measured. Potential interactions with SARS-CoV-2 vaccination, education and sex were explored in stratified analyses and tested by including interaction terms and using likelihood ratio tests. FINDINGS: Individuals with AUD had an increased absolute and relative risk of adverse outcomes, including hospitalization [incidence rate ratio (IRR) = 1.72, 95% confidence interval (CI) = 1.51-1.95], intensive care (IRR = 1.47, 95% CI = 1.07-2.02) and 60-day mortality [mortality rate ratio (MRR) = 2.35, 95% CI = 1.94-2.85] compared with SARS-CoV-2-positive individuals without AUD. Irrespective of AUD, highest risks of these adverse health outcomes were observed for individuals not vaccinated against SARS-CoV-2 infection, for individuals of low educational level and in males. However, for all-cause mortality throughout the follow-up period, SARS-CoV-2 infection showed a lower relative mortality risk increase, whereas being unvaccinated showed a higher relative mortality risk increase, in individuals with AUD than in the reference population without AUD (P of interaction tests < 0.0001). CONCLUSIONS: Both alcohol use disorder and being unvaccinated for SARS-CoV-2 appear to be independent risk factors for adverse health outcomes following SARS-CoV-2 infection.

An Exploratory Analysis of Firefighter Reproduction through Survey Data and Biomonitoring.

Firefighters are occupationally exposed to chemicals that may affect fertility. To investigate this effect, firefighters were recruited to contribute blood, urine, breast milk or semen samples to (1) evaluate chemical concentrations and semen parameters against fertility standards and the general population; (2) assess correlations between chemical concentrations and demographics, fire exposure and reproductive history; and (3) consider how occupational exposures may affect reproduction. A total of 774 firefighters completed the online survey, and 97 firefighters produced 125 urine samples, 113 plasma samples, 46 breast milk samples and 23 semen samples. Blood, urine and breast milk samples were analysed for chemical concentrations (semivolatile organic compounds, volatile organic compounds, metals). Semen samples were analysed for quality (volume, count, motility, morphology). Firefighter semen parameters were below WHO reference values across multiple parameters. Self-reported rates of miscarriage were higher than the general population (22% vs. 12-15%) and in line with prior firefighter studies. Estimated daily intake for infants was above reference values for multiple chemicals in breast milk. More frequent fire incident exposure (more than once per fortnight), longer duration of employment (≥15 years) or not always using a breathing apparatus demonstrated significantly higher concentrations across a range of investigated chemicals. Findings of this study warrant further research surrounding the risk occupational exposure has on reproduction.

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.

Association of homelessness and skin conditions: a Danish population-based cohort study.

BACKGROUND: Research has linked homelessness with an increased risk of skin conditions. However, representative studies of diagnosis-specific information on skin conditions in people experiencing homelessness are lacking. OBJECTIVES: To examine the association between homelessness and diagnosed skin conditions, prescribed medication and type of -consultation. METHODS: This cohort study included data from the Danish nationwide health, social and administrative registers from 1 January 1999 to 31 December 2018. All people of Danish origin living in Denmark and aged at least 15 years at some point during the study period were included. Homelessness, measured by homeless shelter contacts, was the exposure. The outcome was any diagnosis of a skin disorder and specific skin disorders recorded in the Danish National Patient Register. Information on diagnostic consultation type (i.e. dermatological, nondermatological and emergency room) and dermatological prescriptions was studied. We estimated adjusted incidence rate ratio (aIRR) (adjusted for sex, age and calendar year) and cumulative incidence. RESULTS: In total, 5 054 238 individuals (50.6% female) were included in the study population, accounting for 73 477 258 person-years at risk, with a start mean (SD) age of 39.4 (21.1) years. Of the total number of individuals, 759 991 (15.0%) received a skin diagnosis and 38 071 (0.7%) experienced homelessness. A 2.31-times [95% confidence interval (CI) 2.25-2.36] higher IRR of any diagnosed skin condition was associated with homelessness, higher for nondermatological and emergency room consultations. Homelessness was associated with a reduced IRR of a skin neoplasm diagnosis (aIRR 0.76, 95% CI 0.71-8.82) compared with no homelessness. By the end of follow-up, 2.8% (95% CI 2.5-3.0) of individuals experiencing homelessness had a skin neoplasm diagnosis vs. 5.1% (95% CI 4.9-5.3) of individuals not experiencing homelessness. Five or more shelter contacts during the first year from first contact was associated with the highest aIRR of any diagnosed skin condition (7.33, 95% CI 5.57-9.65) compared with no contacts. CONCLUSIONS: Individuals experiencing homelessness have high rates of most diagnosed skin conditions, but a lower occurrence of skin cancer diagnosis. Diagnostic and medical patterns for skin disorders differed clearly between people experiencing homelessness and individuals without these experiences. The time after first homeless shelter contact is an important window of opportunity for mitigating and preventing skin disorders.

Clinical Recovery and Long-Term Association of Specialized Early Intervention Services vs Treatment as Usual Among Individuals With First-Episode Schizophrenia Spectrum Disorder: 20-Year Follow-up of the OPUS Trial.

Importance: The OPUS 20-year follow-up is the longest follow-up of a randomized clinical trial testing early intervention services (EIS) among individuals with first-episode schizophrenia spectrum disorder. Objective: To report on long-term associations of EIS compared with treatment as usual (TAU) for first-episode schizophrenia spectrum disorder. Design, Setting, and Participants: A total of 547 individuals were included in this Danish multicenter randomized clinical trial between January 1998 and December 2000 and allocated to early intervention program group (OPUS) or TAU. Raters who were blinded to the original treatment performed the 20-year follow-up. A population-based sample aged 18 to 45 years with first-episode schizophrenia spectrum disorder were included. Individuals were excluded if they were treated with antipsychotics (>12 weeks prior to randomization), had substance-induced psychosis, had mental disability, or had organic mental disorders. Analysis took place between December 2021 and August 2022. Interventions: EIS (OPUS) consisted of 2 years of assertive community treatment including social skill training, psychoeducation, and family involvement by a multidisciplinary team. TAU consisted of the available community mental health treatment. Main Outcomes and Measures: Psychopathological and functional outcomes, mortality, days of psychiatric hospitalizations, number of psychiatric outpatient contacts, use of supported housing/homeless shelters, symptom remission, and clinical recovery. Results: Of 547 participants, 164 (30%) were interviewed at 20-year follow-up (mean [SD] age, 45.9 [5.6] years; 85 [51.8%] female). No significant differences were found between the OPUS group compared with the TAU group on global functional levels (estimated mean difference, -3.72 [95% CI, -7.67 to 0.22]; P = .06), psychotic symptom dimensions (estimated mean difference, 0.14 [95% CI, -0.25 to 0.52]; P = .48), and negative symptom dimensions (estimated mean difference, 0.13 [95% CI, -0.18 to 0.44]; P = .41). The mortality rate was 13.1% (n = 36) in the OPUS group and 15.1% (n = 41) in the TAU group. Likewise, no differences were found 10 to 20 years after randomization between the OPUS and TAU groups on days of psychiatric hospitalizations (incidence rate ratio, 1.20 [95% CI, 0.73-1.20]; P = .46) or number of outpatient contacts (incidence rate ratio, 1.20 [95% CI, 0.89-1.61]; P = .24). Of the entire sample, 53 participants (40%) were in symptom remission and 23 (18%) were in clinical recovery. Conclusions and Relevance: In this follow-up study of a randomized clinical trial, no differences between 2 years of EIS vs TAU among individuals with diagnosed schizophrenia spectrum disorders at 20 years were found. New initiatives are needed to maintain the positive outcomes achieved after 2 years of EIS and furthermore improve very long-term outcomes. While registry data was without attrition, interpretation of clinical assessments are limited by high attrition rate. However, this attrition bias most likely confirms the lack of an observed long-term association of OPUS with outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT00157313.

Association between SARS-CoV-2 infection and self-harm: Danish nationwide register-based cohort study.

BACKGROUND: Case studies have linked SARS-CoV-2 infection to suicidal behaviour. However, conclusive evidence is lacking. AIMS: To examine whether a history of SARS-CoV-2 infection or SARS-CoV-2-related hospital admission was associated with self-harm in the general population and in high-risk groups. METHOD: A cohort design was applied to nationwide data on all people aged ≥15 years and living in Denmark between 27 February 2020 and 15 October 2021. Exposure was identified as having had a positive SARS-CoV-2 PCR test, and further assessed as SARS-CoV-2-related hospital admission. Rates of probable self-harm were examined using adjusted incidence rate ratios (aIRRs). The following subgroups were identified: (a) lower educational level, (b) chronic medical conditions, (c) disability pension, (d) mental disorders, (e) substance use disorders, and history of (f) homelessness and (g) imprisonment. RESULTS: Among 4 412 248 included individuals, 260 663 (5.9%) had tested positive for SARS-CoV-2. Out of 5453 individuals presenting with self-harm, 131 (2.4%) had been infected. Individuals with a history of a positive SARS-CoV-2 test result had an aIRR for self-harm of 0.86 (95% CI 0.72-1.03) compared with those without. High rates were found after a SARS-CoV-2-related hospital admission (aIRR = 7.68; 95% CI 5.61-10.51) or a non-SARS-CoV-2-related admission (aIRR = 10.27; 95% CI 9.65-10.93) versus non-infected and not admitted. In sensitivity analyses with a more restrictive definition of self-harm, a positive PCR test was associated with lower rates of self-harm. CONCLUSIONS: Individuals with a PCR-confirmed SARS-CoV-2 infection did not have higher rates of self-harm than those without. Hospital admission in general, rather than being SARS-CoV-2 positive. seemed to be linked to elevated rates of self-harm.

First indication of perfluoroalkyl substances in human serum from Papua New Guinea.

Human biomonitoring programs of per- and polyfluoroalkyl substances (PFAS) have been conducted around the world to assess human exposure and health risk. Inquiry into population PFAS levels in a socioeconomically and geographically unique region such as the Pacific Island Papua New Guinea, may provide new insights into PFAS exposure pathways and sources. This study presented the first indication of PFAS exposure in the Papua New Guinea population. De-identified serum samples were pooled from surplus pathology serum samples collected between 2019 and 2020. A total of 11 PFAS were detected in the serum pools including 10 perfluoroalkyl acids (PFAA) and 9Cl-F53B (a perfluorooctane sulfonic acid - PFOS alternative). The observed PFAA profile was somewhat similar to that observed for general population data of other countries such as Australia, Malaysia, and Canada suggesting similar exposure sources and/or pathways. However, PFAS concentrations were consistently lower than concentrations in the serum measured in pools obtained from Australia. The detection of 9Cl-F53B in all pools was a new finding which might be related to exposure from locally industrial sources.

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.

Apparent Half-Lives of Chlorinated-Perfluorooctane Sulfonate and Perfluorooctane Sulfonate Isomers in Aviation Firefighters.

Elevated levels of perfluorooctane sulfonate (PFOS) and elevated detection frequency of chloro-substituted PFOS have been reported in Australian firefighters with historical exposure to aqueous-film forming foam (AFFF). The aim of this study is to estimate the apparent half-lives of Cl-PFOS and PFOS isomers in firefighters following the end of exposure to 3M-AFFF. Paired serum samples from 120 firefighters, collected approximately five years apart, were analyzed for 8-Cl-PFOS (8-chloroperfluoro-1-octanesulfonic acid) and PFOS isomers via targeted LC-MS/MS. Apparent half-life was estimated by assuming a first order-elimination model. Cl-PFOS was detected in 93% of all initial serum samples (

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.

Adverse SARS-CoV-2-associated outcomes among people experiencing social marginalisation and psychiatric vulnerability: A population-based cohort study among 4,4 million people.

Background: Knowledge of the adverse problems related to SARS-CoV-2 infection in marginalised and deprived groups may help to prioritise more preventive efforts in these groups. We examined adverse outcomes associated with SARS-CoV-2 infection among vulnerable segments of society. Methods: Using health and administrative registers, a population-based cohort study of 4.4 million Danes aged at least 15 years from 27 February 2020 to 15 October 2021 was performed. People with 1) low educational level, 2) homelessness, 3) imprisonment, 4) substance abuse, 5) supported psychiatric housing, 6) psychiatric admission, and 7) severe mental illness were main exposure groups. Chronic medical conditions were included for comparison. COVID-19-related outcomes were: 1) hospitalisation, 2) intensive care, 3) 60-day mortality, and 4) overall mortality. PCR-confirmed SARS-CoV-2 infection and PCR-testing were also studied. Poisson regression analysis was used to compute adjusted incidence and mortality rate ratios (IRRs, MRRs). Findings: Using health and administrative registers, we performed a population-based cohort study of 4,412,382 individuals (mean age 48 years; 51% females). In all, 257,450 (5·8%) individuals had a PCR-confirmed SARS-CoV-2 infection. After adjustment for age, calendar time, and sex, we found that especially people experiencing homelessness had high risk of hospitalisation (IRR 4·36, 95% CI, 3·09-6·14), intensive care (IRR 3·12, 95% CI 1·29-7·52), and death (MRR 8·17, 95% CI, 3·66-18·25) compared with people without such experiences, but increased risk was found for all studied groups. Furthermore, after full adjustment, including for status of vaccination against SARS-CoV-2 infection, individuals with experiences of homelessness and a PCR-confirmed SARS-CoV-2 infection had 41-times (95% CI, 24·84-68·44) higher risk of all-cause death during the study period compared with individuals without. Supported psychiatric housing was linked to almost 3-times higher risk of hospitalisation and 60-day mortality following SARS-CoV-2 infection compared with the general population with other living circumstances. Interpretation: Socially marginalised and psychiatrically vulnerable individuals had substantially elevated risks of adverse health outcomes following SARS-CoV-2 infection. The results highlight that pandemic preparedness should address inequalities in health, including infection prevention and vaccination of vulnerable groups. Funding: Novo Nordisk Foundation.

Perturbation of the gut microbiome in wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated PFAS levels.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent and pervasive. Understanding the toxicity of PFAS to wildlife is difficult, both due to the complexity of biotic and abiotic perturbations in the taxa under study and the practical and ethical problems associated with studying the impacts of environmental pollutants on free living wildlife. One avenue of inquiry into the effects of environmental pollutants, such as PFAS, is assessing the impact on the host gut microbiome. Here we show the microbial composition and biochemical functional outputs from the gut microbiome of sampled faeces from euthanised and necropsied wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated PFAS levels. The microbial community composition was profiled by 16S rRNA gene sequencing using a Nanopore MinION and the biochemical functional outputs of the gut microbiome were profiled using a combination of targeted central carbon metabolism metabolomics using liquid chromatography coupled to a triple quadrupole mass spectrometer (LC-QqQ-MS) and untargeted metabolomics using liquid chromatography coupled to a quadrupole time of flight mass spectrometer (LC-QToF-MS). Total PFAS was measured in the turtle serum using standard methods. These preliminary data demonstrated a 60-fold PFAS increase in impacted turtles compared to the sampled aquatic environment. The microbiome community was also impacted in the PFAS exposed turtles, with the ratio of Firmicutes-to-Bacteroidetes rising from 1.4 at the reference site to 5.5 at the PFAS impacted site. This ratio increase is indicative of host stress and dysfunction of the gut microbiome that was correlated with the biochemical metabolic function data, metabolites observed that are indications of stress and inflammation in the gut microbiome. Utilising the gut microbiome of sampled faeces collected from freshwater turtles provides a non-destructive avenue for investigating the impacts of PFAS in native wildlife, and provides an avenue to explore other contaminants in higher-order taxa within the environment.

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.

Vaccination against SARS-CoV-2 infection among vulnerable and marginalised population groups in Denmark: A nationwide population-based study.

Background: Social deprivation, psychiatric and medical disorders have been associated with increased risk of infection and severe COVID-19-related health problems. We aimed to study the rates of SARS-CoV-2 vaccination in these high-risk groups. Methods: Using health, vaccination, and administrative registers, we performed a population-based cohort study including all Danish residents aged at least 15 years, December 27, 2020, to October 15, 2021. Population groups were people experiencing: (1) homelessness, (2) imprisonment, (3) substance abuse, (4) severe mental illness, (5) supported psychiatric housing, (6) psychiatric admission, and (7) chronic medical condition. The outcome was vaccine uptake of two doses against SARS-CoV-2 infection. We calculated cumulative vaccine uptake and adjusted vaccination incidence rate ratios (IRRs) relative to the general population by sex and population group. Findings: The cohort included 4,935,344 individuals, of whom 4,277,380 (86·7%) received two doses of vaccine. Lower cumulative vaccine uptake was found for all socially deprived and psychiatrically vulnerable population groups compared with the general population. Lowest uptake was found for people below 65 years experiencing homelessness (54·6%, 95% confidence interval (CI) 53·4-55·8, p<0·0001). After adjustment for age and calendar time, homelessness was associated with markedly lower rates of vaccine uptake (IRR 0·5, 95% CI 0·5-0·6 in males and 0·4, 0·4-0·5 in females) with similar results for imprisonment. Lower vaccine uptake was also found for most of the psychiatric groups with the lower IRR for substance abuse (IRR 0·7, 0·7-0·7 in males and 0·8, 0·8-0·8 in females). Individuals with new-onset severe mental illness and, especially, those in supported psychiatric housing and with chronic medical conditions had the highest vaccine uptake among the studied population groups. Interpretation: Especially, socially deprived population groups, but also individuals with psychiatric vulnerability need higher priority in the implementation of the vaccination strategy to increase equity in immunization uptake. Funding: Novo Nordisk Foundation.