APOE×BDNF Interaction and Poorer Cognitive Outcomes Among Veterans With Mild Traumatic Brain Injury: An Exploratory Study.

OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.

Bone mineral density and body composition in Australians following plant-based diets vs. regular meat diets.

Background and aims: Bone mineral density (BMD) and body composition play an important role in maintaining metabolic health and physical functioning. Plant-based diets (PBDs) are known to be lower in protein and calcium, which can impact BMD and body composition. This study aimed to investigate the relationship between various PBDs compared to regular meat diet and whole-body BMD, body composition, and weight status. Methods: A cross-sectional study was conducted with adults (n = 240) aged 30-75 years, who habitually followed dietary patterns: vegan, lacto-vegetarian, pesco-vegetarian, semi-vegetarian, or regular meat eater (48 per group). Parameters were measured using dual-energy x-ray absorptiometry (DXA), and multivariable regression analyses were used to adjust for lifestyle confounders, socioeconomic factors, and BMI. Results: After adjustments, whole-body BMD and body composition were not significantly different between those following PBDs and regular meat diets, except for lacto-ovo vegetarians, who had significantly lower lean mass by -1.46 kg (CI: -2.78, -0.13). Moreover, lacto-ovo vegetarians had a significantly lower T-score by -0.41 SD (CI: -0.81, -0.01) compared to regular meat eaters. Waist circumference was significantly lower in individuals adhering to a PBD compared to a regular meat diet: vegans by -4.67 cm (CI: -8.10, -1.24), lacto-ovo vegetarians by -3.92 cm (CI: -6.60, -1.23), pesco-vegetarians by -3.24 cm (CI: -6.09, -0.39), and semi-vegetarians by -5.18 cm (CI: -7.79, -2.57). There were no significant differences in lean mass (%), fat mass (% and total), android/gynoid measures, body weight, or BMI across dietary patterns. All dietary patterns met the recommended dietary intake for calcium and protein, and 25-hydroxy-vitamin D status was comparable across groups. Conclusions: This cross-sectional study found that adhering to a PBD characterized by varying degrees of dairy and meat restriction is not associated with meaningful changes in BMD or body composition, provided that the dietary patterns are planned appropriately with adequate levels of calcium and protein.

Study protocol for an adaptive, multi-arm, multi-stage (MAMS) randomised controlled trial of brief remotely delivered psychosocial interventions for people with serious mental health problems who have experienced a recent suicidal crisis: Remote Approaches to Psychosocial Intervention Delivery (RAPID).

BACKGROUND: People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. METHODS: A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). DISCUSSION: There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. TRIAL REGISTRATION: ISRCTN33079589. Registered on June 20, 2022.

Homeostatic measure of insulin resistance is associated with future asthma exacerbations: a 1-year prospective cohort study.

BACKGROUND AND AIMS: Recent evidence suggests that insulin resistance affects asthma outcomes; however, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood. OBJECTIVES: To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IRhigh group and HOMA-IRlow group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features, and a 1-year follow-up was conducted to study the exacerbations. A negative binomial regression model was used to analyze the association between HOMA-IR and AEs. RESULTS: Compared with the patients in the HOMA-IRlow group (n = 564), patients in the HOMA-IRhigh group (n = 61) had higher levels of BMI, higher waist circumference and waist/hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins (HDL), more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IRhigh group had a significantly increased risk for moderate-to-severe AEs (adjusted incidence rate ratio (aIRR) = 2.26, 95% confidence interval (CI) = [1.38, 3.70]), severe AEs (aIRR = 2.42, 95% CI = [1.26, 4.67]), hospitalization(aIRR = 2.54, 95% CI = [1.20, 5.38]), and emergency visits (aIRR = 3.04, 95% CI = [1.80, 8.53]). CONCLUSION: HOMA-IR was associated with asthma-related clinical features, and airway inflammation, as well as being an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.

A tale of two PG systems: A comparison of the two most widely used continuous probabilistic genotyping systems in the United States.

The development of probabilistic genotyping (PG) systems to quantitatively analyze DNA mixture samples has been transformative in forensic science. TrueAllele® Casework (TA) and STRmix™ (STRmix) are the two most widely used PG systems in the United States. The two systems were challenged with 48 two-, three-, and four-person mock casework samples, for a total of 152 likelihood ratio (LR) comparisons. TA and STRmix converged on the same result (supportive, non-supportive, or inconclusive) for ~91% of contributor-specific comparisons. Where moderate or substantial differences in log(LR) values were observed, 9% affected the conclusion of the reference association to the mixture. The PG systems exhibited high correlations for estimated contributor-specific template quantities (~92%) and log(LR)s produced (>88%). When the log(LR)s for only low-template contributors (<100 pg) were compared, the R2 value dropped to ~68% and the difference became statistically significant. Of the 14 contributor comparisons where the conclusion differed, two were contradictory (supportive vs. non-supportive) and 12 were either inconclusive versus non-supportive or inconclusive versus supportive. The differing results were likely due to dissimilarities in the mixture input file as STRmix uses a lab-defined analytical threshold (AT) and TA models to 10 RFUs for each electropherogram. When 7 of the 14 mixtures were reanalyzed by STRmix using a 10 RFU AT, the log(LR)s for the low-template contributors became more similar to TAs. This study shows that while both systems may produce accurate and calibrated LRs, their results can deviate, especially for low-template, degraded contributors, and the deviation is generally predictable.

Effects of Moderate- Versus Vigorous-Intensity Exercise Training on Asthma Outcomes in Adults.

BACKGROUND: The therapeutic effects of exercise have prompted calls for it to be embedded into standard asthma care, but evidence informing the optimal exercise intensity is lacking. OBJECTIVE: This study aimed to compare the effects of moderate- and vigorous-intensity aerobic exercise training on asthma outcomes and inflammation. METHODS: This was a 12-week randomized controlled trial in 46 adults with asthma randomized to either (1) 45-minute moderate-intensity exercise training 3 times/wk, (2) 30-minute vigorous-intensity exercise training 3 times/wk, or (3) the control group. Asthma-related quality of life (AQLQ), asthma control (ACQ), cardiorespiratory fitness, body composition, and airway and systemic inflammation were assessed before and after the intervention. RESULTS: Forty-one participants completed the study (89% retention). The moderate-intensity group had a statistically and clinically significant improvement in AQLQ (0.63 [0.33-0.93], P < .001) and ACQ (-0.51 [-0.83 to -0.19], P = .003) relative to control. The vigorous-intensity group had a statistically, but not clinically, significant improvement in AQLQ (0.46 [0.14-0.80], P = .007) and ACQ (-0.36 [-0.69 to -0.02], P = .040) relative to control. After moderate-intensity training, there was a reduction in sputum macrophage (-1341 [-2491 to -191] × 104/mL, P = .024) and lymphocyte (-114 [-220 to -8] × 104/mL, P = .036) counts relative to control. A reduction in android fat mass, but not a change in fitness, was associated with improved AQLQ (rs = -0.341, P = .030) and reduced sputum IL-6 (rs = 0.422, P = .013). CONCLUSIONS: Our findings suggest that both moderate-intensity and vigorous-intensity aerobic exercise training are associated with improvements in clinical asthma outcomes and, therefore, both intensities could be recommended as an adjuvant asthma therapy.

Critical Success Factors for Intersectoral Collaboration: Homelessness and COVID-19 - Case Studies and Learnings from an Australian City.

Introduction: The COVID-19 pandemic disproportionally impacted people experiencing homelessness, including people sleeping rough, people in temporary accommodation and those living in boarding houses. This paper reports on intersectoral responses across six health and social care agencies in Inner Sydney, New South Wales, Australia. Prior to the pandemic the six agencies had established an Intersectoral Homelessness Health Strategy (IHHS), in recognition of the need for intersectoral collaboration to address the complex health needs of people experiencing homelessness. Description: The governance structure of the IHHS provided a platform for several innovative intersectoral responses to the pandemic. A realist informed framework was used to select, describe, and analyse case studies of intersectoral collaboration. Discussion: The resultant six critical success factors (trust, shared ways of working, agile collaboration, communication mechanisms, authorising environment, and sustained momentum), align with the existing literature that explores effective intersectoral collaboration in complex health or social care settings. This paper goes further by describing intersectoral collaboration 'in action', setting a strong foundation for future collaborative initiatives. Conclusion: While there is no single right approach to undertaking intersectoral collaboration, which is highly context specific, the six critical success factors identified could be applied to other health issues where dynamic collaboration and integration of healthcare is needed.

DIGIPREDICT: physiological, behavioural and environmental predictors of asthma attacks-a prospective observational study using digital markers and artificial intelligence-study protocol.

INTRODUCTION: Asthma attacks are a leading cause of morbidity and mortality but are preventable in most if detected and treated promptly. However, the changes that occur physiologically and behaviourally in the days and weeks preceding an attack are not always recognised, highlighting a potential role for technology. The aim of this study 'DIGIPREDICT' is to identify early digital markers of asthma attacks using sensors embedded in smart devices including watches and inhalers, and leverage health and environmental datasets and artificial intelligence, to develop a risk prediction model to provide an early, personalised warning of asthma attacks. METHODS AND ANALYSIS: A prospective sample of 300 people, 12 years or older, with a history of a moderate or severe asthma attack in the last 12 months will be recruited in New Zealand. Each participant will be given a smart watch (to assess physiological measures such as heart and respiratory rate), peak flow meter, smart inhaler (to assess adherence and inhalation) and a cough monitoring application to use regularly over 6 months with fortnightly questionnaires on asthma control and well-being. Data on sociodemographics, asthma control, lung function, dietary intake, medical history and technology acceptance will be collected at baseline and at 6 months. Asthma attacks will be measured by self-report and confirmed with clinical records. The collected data, along with environmental data on weather and air quality, will be analysed using machine learning to develop a risk prediction model for asthma attacks. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the New Zealand Health and Disability Ethics Committee (2023 FULL 13541). Enrolment began in August 2023. Results will be presented at local, national and international meetings, including dissemination via community groups, and submission for publication to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12623000764639; Australian New Zealand Clinical Trials Registry.

Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype.

OBJECTIVE: Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status - particularly possession of the apolipoprotein E (APOE) ε4 allele - can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories. METHODS: 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24-50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4-) on MIST scores. RESULTS: Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (p=.002, ηp2 =.160), Time Cue (p = .003, ηp2 =.157), and PM Total (p = .016, ηp2 =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, ηp2 =.113) and PM Total (p = .048, ηp2 = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4- Veterans on the MIST 15-min delay subscale (p = .031, ηp2 = .150). CONCLUSIONS: mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.

Protein Intake and Physical Activity Levels as Determinants of Sarcopenia Risk in Community-Dwelling Older Adults.

Community screening for sarcopenia is complex, with barriers including access to specialized equipment and trained staff to conduct body composition, strength and function assessment. In the current study, self-reported dietary protein intake and physical activity (PA) in adults ≥65 years was assessed relative to sarcopenia risk, as determined by body composition, strength and physical function assessments, consistent with the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Of those screened (n = 632), 92 participants (77% female) were assessed as being at high risk of developing sarcopenia on the basis of dietary protein intake ≤1 g∙kg-1∙day-1 [0.9 (0.7-0.9) g∙kg-1∙day-1] and moderate intensity physical activity <150 min.week-1. A further 31 participants (65% female) were defined as being at low risk, with both protein intake [1.2 (1.1-1.5) g∙kg-1∙day-1] and PA greater than the cut-off values. High-risk participants had reduced % lean mass [53.5 (7.8)% versus 54.8 (6.1)%, p < 0.001] and impaired strength and physical function. Notably, high-risk females exhibited greater deficits in lean mass and strength, with minimal differences between groups for males. In community-dwelling older adults, self-reported low protein intake and low weekly PA is associated with heightened risk for sarcopenia, particularly in older women. Future research should determine whether early intervention in older adults with low protein intake and PA attenuates functional decline.

Cardiovascular Disease Risk in Individuals Following Plant-Based Dietary Patterns Compared to Regular Meat-Eaters.

Plant-based diets (PBDs) have been associated with a lower risk of cardiovascular disease (CVD). The aim was to investigate the predicted 5-year and 10-year risk of developing CVD in individuals following PBDs compared to regular meat-eating diets. This cross-sectional study included n = 240 middle-aged adults habitually consuming dietary patterns for ≥6 months: vegan, lacto-ovo vegetarian (LOV), pesco-vegetarian (PV), semi-vegetarian (SV) or regular meat-eater (RME) (n = 48 per group). Predicted 5-year and 10-year CVD risks were quantified using the Framingham Risk Equation and the Australian Absolute CVD risk calculator, respectively. Multivariable regression analysis was used to adjust for age, sex, smoking status, physical activity, alcohol use and BMI. Over three-quarters of the participants were women, mean age of 53.8 yrs. After adjustments for potential confounders, there was no difference in the predicted risk of CVD between regular-meat diets and PBDs, although crude analyses revealed that vegans had a lower 5-year and 10-year predicted risk of CVD compared to RMEs. SVs, PVs and LOVs had lower CVD risk scores, however, not significantly. Vegans had a favourable cardiometabolic risk profile including significantly lower serum lipid levels, fasting blood glucose and dietary fats and higher dietary fibre intake compared to RMEs. This was the first study to purposefully sample Australians habitually following PBDs. We found that PBDs do not independently influence the predicted risk of CVD, although PBDs tended to have lower risk and vegans had significantly lower cardiometabolic risk factors for CVD.

The assessment of dietary carotenoid intake of the Cardio-Med FFQ using food records and biomarkers in an Australian cardiology cohort: a pilot validation.

Dietary carotenoids are associated with lower risk of CHD. Assessment of dietary carotenoid intake using questionnaires can be susceptible to measurement error. Consequently, there is a need to validate data collected from FFQs which measure carotenoid intake. This study aimed to assess the performance of the Cardio-Med Survey Tool (CMST)-FFQ-version 2 (v2) as a measure of dietary carotenoid intake over 12-months against plasma carotenoids biomarkers and 7-Day Food Records (7DFR) in an Australian cardiology cohort. Dietary carotenoid intakes (ß- and α-carotene, lycopene, ß-cryptoxanthin and lutein/zeaxanthin) were assessed using the 105-item CMST-FFQ-v2 and compared to intakes measured by 7DFR and plasma carotenoid concentrations. Correlation coefficients were calculated between each dietary method, and validity coefficients (VCs) were calculated between each dietary method and theoretical true intake using the 'methods of triads'. Thirty-nine participants aged 37-77 years with CHD participated in the cross-sectional study. The correlation between FFQ and plasma carotenoids were largest and significant for ß-carotene (0.39, p=0.01), total carotenoids (0.37, p=0.02) and ß-cryptoxanthin (0.33, p=0.04), with weakest correlations observed for α-carotene (0.21, p=0.21) and lycopene (0.21, p=0.21). The FFQ VCs were moderate (0.3-0.6) or larger for all measured carotenoids. The strongest were observed for total carotenoids (0.61) and ß-carotene (0.59), while the weakest were observed for α-carotene (0.33) and lycopene (0.37). In conclusion, the CMST-FFQ-v2 measured dietary carotenoids intakes with moderate confidence for most carotenoids, however, there was less confidence in ability to measure α-carotene and lycopene intake, thus further research is warranted using a larger sample.

A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare.

BACKGROUND: Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. METHODS: A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman's multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. RESULTS: Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of 'accessible and timely', 'person-centred', and values of 'dignity and respect' and 'kindness with compassion' were most prevalent. Among the three patient experience surveys identified, 'accessible and timely' and 'person-centred' were the most frequent domains. The least frequently highlighted domains and values were 'equitable' and 'holistic'. No questions addressed the 'safety' domain. CONCLUSIONS: The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of 'Kindness and compassion' require further emphasis when seeking feedback on healthcare experiences and the domains of 'safety', 'equitable', and 'efficiency' are not adequately represented in existing patient experience surveys.

Data-driven classification of cognitively normal and mild cognitive impairment subtypes predicts progression in the NACC dataset.

INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.

COVID-19 vaccination of at-risk and marginalised groups: recentering the state in vaccine uptake.

Recent studies have used the World Health Organization's new Behavioural and Social Drivers (BeSD) framework to analyse vaccine uptake. However, this study of COVID-19 vaccination among marginalised population groups highlights the framework's limitations regarding the centrality of the state in shaping people's vaccination intentions in high income countries. We conducted interviews and focus groups with service providers and community members to explore COVID-19 vaccination amongst Western Australians experiencing homelessness and/or from other marginalised populations (such as people with substance use dependence). Analysing this data iteratively to emphasise the state's role and functions, we elaborate how trauma and mistrust of government drive thoughts, feelings, and social interactions regarding vaccination programs, which are mutually reinforcing and which inhibit individuals' willingness to engage. Government systems that leave some populations behind increase those populations' susceptibility to misinformation. Policies may generate new unintended problems: social service providers worried about vaccine advocacy damaging clients' trust, especially in the context of vaccine mandates. Reframing the state's responsibility for designing culturally and socially appropriate services, we outline how end-users and trusted providers can lead this process. We share a new framework, "Recentering the State in Vaccine Uptake," arising from our analyses.

Tracking deaths of people who have experienced homelessness: a dynamic cohort study in an Australian city.

OBJECTIVE: Life expectancy and rates of premature death are fundamental markers of health and social equity globally, and measures on which people experiencing homelessness face enormous disparities. However, unlike for other population groups with similar disparities, concerted government action to reduce homeless mortality is rare, partly due to a lack of reliable, timely data. Contemporaneous tracking of homeless deaths is required to render such deaths less invisible and measure trends over time. Drawing on multiple data sources as recommended by the US National Health Care for the Homeless Council's seminal Homeless Mortality Data Toolkit, we routinely and contemporaneously capture, verify and report on deaths occurring among people who have experienced homelessness in the Australian city of Perth. DESIGN: Dynamic cohort study. SETTING: Perth, Western Australia, Australia, between 2016 and 2022, with deaths examined between 2020 and 2022. PARTICIPANTS: For this study, the cohort comprised 8753 people who experienced homelessness in Perth, with 'recruitment' into the cohort governed by engagement with one or more local homelessness services and programmes over the period. OUTCOME MEASURES: Number and median age-at-death statistics. RESULTS: There were 360 deaths over the 3-year period, which is likely an undercount. The median age at death was 50 years, >3 decades below the current Australian median age at death of 82 years. Aboriginal people accounted for 30% of the deaths. CONCLUSION: The ongoing poor health and premature death of people who have experienced homeless are indictments on our society. Triangulation of multiple data sources is required to identify and monitor deaths among homeless populations. Timely, verified data on homeless mortality are important for galvanising action and accountability, and targets should be set to reduce the observed three-decade life expectancy chasm.

A crisis planning and monitoring intervention to reduce compulsory hospital readmissions (FINCH study): protocol for a randomised controlled feasibility study.

BACKGROUND: Rates of compulsory (also known as involuntary) detention under mental health legislation have been rising over several decades in countries including England. Avoiding such detentions should be a high priority given their potentially traumatic nature and departure from usual ethical principles of consent and collaboration. Those who have been detained previously are at high risk of being detained again, and thus a priority group for preventive interventions. In a very sparse literature, interventions based on crisis planning emerge as having more supporting evidence than other approaches to preventing compulsory detention. METHOD: We have adapted and manualised an intervention previously trialled in Zürich Switzerland, aimed at reducing future compulsory detentions among people being discharged following a psychiatric admission that has included a period of compulsory detention. A co-production group including people with relevant lived and clinical experience has co-designed the adaptations to the intervention, drawing on evidence on crisis planning and self-management and on qualitative interviews with service users and clinicians. We will conduct a randomised controlled feasibility trial of the intervention, randomising 80 participants to either the intervention in addition to usual care, or usual care only. Feasibility and acceptability of the intervention and trial procedures will be assessed through process evaluation (including rates of randomisation, recruitment, and retention) and qualitative interviews. We will also assess and report on planned trial outcomes. The planned primary outcome for a full trial is repeat compulsory detention within one year of randomisation, and secondary outcomes include compulsory detention within 2 years, and symptoms, service satisfaction, self-rated recovery, self-management confidence, and service engagement. A health economic evaluation is also included. DISCUSSION: This feasibility study, and any subsequent full trial, will add to a currently limited literature on interventions to prevent involuntary detention, a goal valued highly by service users, carers, clinicians, and policymakers. There are significant potential impediments to recruiting and retaining this group, whose experiences of mental health care have often been negative and traumatising, and who are at high risk of disengagement. TRIAL REGISTRATION: ISRCTN, ISRCTN11627644. Registered 25th May 2022, https://www.isrctn.com/ISRCTN11627644 .

Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia.

This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.

Vape stores in Western Australia: growth, proximity to schools and socio-economic gradient of density.

OBJECTIVE: To audit the number and location of dedicated e-cigarette retailers ("vape stores") in Western Australian (WA), measure proximity to schools and model the association between vape store density and socio-economic disadvantage. METHODS: Vape stores were identified via internet search and geocoded. Proximity to schools was measured. Regression modelling was used to investigate the association between vape store density and socio-economic disadvantage. RESULTS: 194 stores were identified, with 88% located within one kilometre of a school. In metropolitan WA, vape store density was nearly seven times higher in the most socio-economically disadvantaged areas than in the least disadvantaged areas (rate ratio 6.9, 95% confidence interval 3.4-15.5). CONCLUSIONS: There has been rapid, recent growth in the number of vape stores in WA, with most located within walking distance of schools. In metropolitan WA, vape store density is strongly associated with socio-economic disadvantage, mirroring the pattern observed globally for tobacco outlets. IMPLICATIONS FOR PUBLIC HEALTH: This is the first Australian study demonstrating that vape stores are more densely located in socio-economically disadvantaged areas. Vape stores' proximity to schools may increase young people's access and exposure to promotional signage. There is a need to address ready e-cigarette availability through strong regulatory and compliance measures.

Apathy After Stroke: Incidence, Symptom Trajectory, and Impact on Quality of Life and Disability

BACKGROUND AND OBJECTIVES: Apathy is one of the most common symptoms following stroke and is often associated with worse functional outcome and poor quality of life (QoL). The trajectory of apathy symptoms has been previously described, and different trajectories have been identified. We determined group and individual changes in apathy symptomatology from the acute phase until 1 year after stroke. We also examined the association of apathy and depression with disability and QoL 1 year after stroke. METHODS: We measured apathy in a cohort of ischemic stroke survivors at 4 time points from 0 to 12 months after stroke. The Apathy Evaluation Scale (AES) and Dimensional Apathy Scale (DAS) were administered at each time point. Where possible we obtained apathy measured from carers. Depression was assessed with the Geriatric Depression Scale (GDS). Disability and QoL were assessed with the modified Rankin Scale (mRS) and 36-Item Short Form Survey (SF-36). We examined the cross-sectional and individual trajectory of apathy symptoms in each dimension and looked at associations of apathy and depression soon after stroke with mRS and SF-36 at 1 year. RESULTS: Of 200 participants enrolled, 165 completed apathy measures at 12 months. Patient-rated apathy scores increased in both tests at the group level (AES: χ2(3) = 9.86, p = 0.019; DAS: χ2(3) = 8.49, p = 0.037) and individual level (AES: ß = 0.13, p = 0.002; DAS ß = 0.13, p = 0.005; DAS: executive ß = 0.08, p < 0.001). By contrast, carer-rated apathy did not significantly increase (AES: χ2(3) = 0.75, p = 0.862; DAS: χ2(3) = 2.45, p = 0.484). Apathy scores were associated with worse mRS and SF-36, although most associations were no longer significant when controlling for depression. GDS was associated with worse mRS and SF-36 after controlling for covariates and apathy (mRS: ß = 0.08, p = 0.006; SF-36 Mental Component Summary: ß = -1.53, p < 0.001; SF-36 Physical Component Summary: ß = -0.57, p = 0.016). DISCUSSION: Self-reported apathy progressively increases after stroke, especially in the executive dimension. Apathy is associated with worse QoL and greater disability, although some of these associations might be mediated by depression.