A Scoping Review of Interventions Targeting the Mental Health of Australian Veterans.

Serving in the military can have significant impacts on the mental health of veterans and their families. Military personnel can be exposed to a range of physical stressors, psychological trauma, risky lifestyle factors, a regimented military culture, and inadequate support when transitioning out of service. This article reviews research on interventions designed to improve the mental health of Australian military veterans in order to synthesise current knowledge and identify gaps in the literature. Our scoping review followed PRISMA recommendations and comprised peer-reviewed literature published since 2000. The review demonstrates a dominance of psychologically driven research paradigms and interventions and a neglect of the importance of social factors in shaping veteran mental health. There is a wide range of interventions available; however, the literature is narrow and limited. We found little evidence that the lived experience of veterans had been harnessed in program design or delivery. We argue the need for a holistic approach that moves beyond psychological and biological understandings of health and wellbeing to incorporate social and cultural determinants. Future research could adopt a stronger multidisciplinary approach, increased socio-cultural understanding, and greater consideration of the lived experience of veterans and their families.

Adaptive design trials in eating disorder research: A scoping review.

OBJECTIVE: This scoping review sought to map the breadth of literature on the use of adaptive design trials in eating disorder research. METHOD: A systematic literature search was conducted in Medline, Scopus, PsycInfo, Emcare, Econlit, CINAHL and ProQuest Dissertations and Theses. Articles were included if they reported on an intervention targeting any type of eating disorder (including anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding or eating disorders), and employed the use of an adaptive design trial to evaluate the intervention. Two independent reviewers screened citations for inclusion, and data abstraction was performed by one reviewer and verified by a second. RESULTS: We identified five adaptive design trials targeting anorexia nervosa, bulimia nervosa and binge-eating disorder conducted in the USA and Australia. All employed adaptive treatment arm switching based on early response to treatment and identified a priori stopping rules. None of the studies included value of information analysis to guide adaptive design decisions and none included lived experience perspectives. DISCUSSION: The limited use of adaptive designs in eating disorder trials represents a missed opportunity to improve enrolment targets, attrition rates, treatment outcomes and trial efficiency. We outline the range of adaptive methodologies, how they could be applied to eating disorder research, and the specific operational and statistical considerations relevant to adaptive design trials. PUBLIC SIGNIFICANCE: Adaptive design trials are increasingly employed as flexible, efficient alternatives to fixed trial designs, but they are not often used in eating disorder research. This first scoping review identified five adaptive design trials targeting anorexia nervosa, bulimia nervosa and binge-eating disorder that employed treatment arm switching adaptive methodology. We make recommendations on the use of adaptive design trials for future eating disorder trials.

OBJETIVO: Esta revisión exploratoria buscó mapear el alcance de la literatura sobre el uso de ensayos de diseño adaptativo en la investigación de trastornos de conducta alimentaria. MÉTODO: Se realizó una búsqueda sistemática de literatura en Medline, Scopus, PsycInfo, Econlit y CINAHL. Se incluyeron artículos que informaban sobre una intervención dirigida a cualquier tipo de trastorno de conducta alimentaria (incluyendo anorexia nerviosa, bulimia nerviosa, trastorno por atracón y otros trastornos de la conducta alimentaria o de la ingestión de alimentos especificados) y empleaban el uso de un ensayo de diseño adaptativo para evaluar la intervención. Dos revisores independientes examinaron las citas para su inclusión, y la abstracción de datos fue realizada por un revisor y verificada por otro. RESULTADOS: Identificamos cinco ensayos de diseño adaptativo dirigidos a la anorexia nerviosa, bulimia nerviosa y trastorno por atracón realizados en Estados Unidos y Australia. Todos emplearon el cambio adaptativo de brazo de tratamiento basado en la respuesta temprana al tratamiento e identificaron reglas de detención a priori. Ninguno de los estudios incluyó análisis del Valor de la Información para guiar las decisiones de diseño adaptativo y ninguno incluyó perspectivas de experiencia vivida. DISCUSIÓN: El uso limitado de diseños adaptativos en ensayos de trastornos de conducta alimentaria representa una oportunidad perdida para mejorar los objetivos de reclutamiento, tasas de deserción, resultados del tratamiento y eficiencia del ensayo. Esbozamos la gama de metodologías adaptativas, cómo podrían aplicarse a la investigación de trastornos de conducta alimentaria, y las consideraciones operativas y estadísticas específicas relevantes para los ensayos de diseño adaptativo. PÚBLICA SIGNIFICANCIA: Los ensayos de diseño adaptativo se emplean cada vez más como alternativas flexibles y eficientes a los diseños de ensayos fijos, pero no se utilizan con frecuencia en la investigación de trastornos de conducta alimentaria. Esta primera revisión exploratoria identificó cinco ensayos de diseño adaptativo dirigidos a la anorexia nerviosa, bulimia nerviosa y trastorno por atracón que emplearon la metodología adaptativa de cambio de brazo de tratamiento. Hacemos recomendaciones sobre el uso de ensayos de diseño adaptativo para futuros ensayos de trastornos de conducta alimentaria.

Lived experience perspectives on eating disorder research: The use of adaptive trials and research priorities.

OBJECTIVE: This novel study sought to understand lived experience and carer perspectives on the use of adaptive trials to evaluate interventions for eating disorders, in addition to understanding the factors and outcomes of most importance in eating disorder research and treatments from a lived experience perspective. METHOD: A total of 73 people with either lived or carer experience consented, 70 started the questionnaire, and 36 (51%) completed all questions. Participants were asked Likert scale and open-ended questions to understand what factors and outcomes of eating disorder interventions were most important to them and understand their pre-existing knowledge of clinical trials. Two videos were then used to explain randomized controlled trials (RCTs) and adaptive trials and participants were asked their opinions, including perceived benefits and concerns, of each trial type. RESULTS: The thematic analysis found two key themes regarding factors important in eating disorder treatment: Person-centred care and Evidence-based and effective treatment; and two key themes regarding outcomes of treatment: Sustained, full recovery and The bigger picture. Both RCTs and adaptive trials were viewed favorably, however, there was a slight preference for adaptive trials. Key themes for both demonstrated perceived benefits and ethical, practical, and scientific considerations unique to each. DISCUSSION: Findings demonstrate the support of adaptive trials in eating disorder interventions from people with lived experience and their carers. It is recommended that researchers consider the use of adaptive designs and the incorporation of lived experience perspectives when designing future intervention trials. PUBLIC SIGNIFICANCE: This novel study found that the use of adaptive trials in eating disorder intervention research is supported by people with lived experience and carers. Furthermore, the factors and outcomes of most importance to participants in this study are comparable to those previously identified in the emerging literature. The use of adaptive designs and the incorporation of lived experience are recommended in further clinical trials.

Prevalence of unmet supportive care needs reported by individuals ever diagnosed with cancer in Australia: a systematic review to support service prioritisation.

PURPOSE: Improved health outcomes for individuals ever diagnosed with cancer require comprehensive, coordinated care that addresses their supportive care needs. Implementing interventions to address these is confounded by a lack of evidence on population needs and a large pool of potential interventions. This systematic review estimates the point prevalence of different supportive care needs stratified by the tool used to measure needs and cancer type in Australia. METHODS: We searched MEDLINE, Embase, and Scopus from 2010 to April 2023 to identify relevant studies published on the prevalence of supportive care needs in Australia. RESULTS: We identified 35 studies that met the inclusion criteria. The highest prevalent unmet need across all cancers was 'fear of cancer spreading' (20.7%) from the Supportive Care Needs Survey Short-Form 34 (SCNS-SF34), ranging from 9.4% for individuals ever diagnosed with haematological cancer to 36.3% for individuals ever diagnosed with gynaecological cancer, and 'concerns about cancer coming back' (17.9%) from the Cancer Survivors' Unmet Needs (CaSUN), ranging from 9.7% for individuals ever diagnosed with prostate cancer to 37.8% for individuals ever diagnosed with breast cancer. Two studies assessed needs in Aboriginal and Torres Strait Islander populations, reporting the highest needs for financial worries (21.1%). CONCLUSIONS: Point prevalence estimates presented here, combined with estimates of the costs and effects of potential interventions, can be used within economic evaluations to inform evidence-based local service provision to address the supportive care needs of individuals ever diagnosed with cancer. IMPLICATIONS FOR CANCER SURVIVORS: Local health services can use local evidence to prioritise the implementation of interventions targeted at unmet needs.

An exploration of healthcare use in older people waiting for and receiving Australian community-based aged care services.

AIM: Home care packages (HCPs) facilitate older individuals to remain at home, with longer HCP wait times associated with increased mortality risk. We analyze healthcare cost data pre- and post-HCP access to inform hypotheses around the effects of healthcare use and mortality risk. METHODS: Regression models were used to assess the impact of delayed HCP access on healthcare costs and to compare costs whilst waiting and in the 6- and 12 month periods post-HCP access for 16 629 older adults. RESULTS: Average wait time for a HCP was 89.7 days (SD = 125.6) during the study period. Wait-time length had no impact on any healthcare cost category or time period. However, total per day healthcare costs were higher in the 6 and 12 months post-receipt of a HCP (AU$61.5, AU$63, respectively) compared with those in the time waiting for a HCP (AU$48.1). Inpatient care accounted for a higher proportion of total healthcare costs post-HCP (AU$45.1, AU$46.3, respectively) compared with in the wait time (AU$30.6), whilst spending on medical services and pharmaceuticals reduced slightly in the 6 month (AU$7.1, AU$6.3) and 12 month (AU$7.2, AU$6.3) post-HCP periods compared with in the wait time (AU$7.9, AU$7.1). CONCLUSIONS: Increased spending post-HCP on inpatient care or non-health support afforded by HCPs may offer protective effects for mortality and risk of admission to aged care. Further research should explore the association between delayed access to inpatient care for geriatric syndromes and mortality to inform recommendations on extensions to residential care outreach services into the community to improve the timely identification of the need for inpatient care. Geriatr Gerontol Int 2023; 23: 899-905.

DAta Linkage to Enhance Cancer Care (DaLECC): Protocol of a Large Australian Data Linkage Study.

Cancer is a leading cause of global morbidity and mortality, accounting for 250 Disability-Adjusted Life Years and 10 million deaths in 2019. Minimising unwarranted variation and ensuring appropriate cost-effective treatment across primary and tertiary care to improve health outcomes is a key health priority. There are few studies that have used linked data to explore healthcare utilisation prior to diagnosis in addition to post-diagnosis patterns of care. This protocol outlines the aims of the DaLECC project and key methodological features of the linked dataset. The primary aim of this project is to explore predictors of variations in pre- and post-cancer diagnosis care, and to explore the economic and health impact of any variation. The cohort of patients includes all South Australian residents diagnosed with cancer between 2011 and 2020, who were recorded on the South Australian Cancer Registry. These cancer registry records are being linked with state and national healthcare databases to capture health service utilisation and costs for a minimum of one-year prior to diagnosis and to a maximum of 10 years post-diagnosis. Healthcare utilisation includes state databases for inpatient separations and emergency department presentations and national databases for Medicare services and pharmaceuticals. Our results will identify barriers to timely receipt of care, estimate the impact of variations in the use of health care, and provide evidence to support interventions to improve health outcomes to inform national and local decisions to enhance the access and uptake of health care services.

The impacts of unmet supportive care needs of cancer survivors in Australia: A qualitative systematic review.

INTRODUCTION: Cancer incidence and survivorship are increasing worldwide. With more people living through and beyond cancer, there is a subsequent increase in their supportive care needs. This systematic review of qualitative studies aimed to describe the impacts of unmet supportive care needs on cancer survivors in Australia. METHODS: Databases MEDLINE, EMBASE and Scopus were searched, and after screening and applying eligibility criteria, 27 qualitative studies were included. Findings were synthesised according to the Supportive Care Framework for Cancer Care, including informational, physical, practical, emotional, psychological, social and spiritual need domains. RESULTS: The systematic review identified impacts of unmet informational, physical, practical, emotional and psychological needs. Frequently identified impacts of unmet informational needs were feelings of abandonment and isolation, distress, confusion and regret. Common impacts of unmet physical and practical needs were financial burden and return-to-work difficulties. Over half of all unmet supportive care needs caused emotional and psychological impacts. CONCLUSIONS: Findings identify the detrimental emotional and psychological impacts resulting from a range of unmet supportive care needs. The review highlights the interconnections between supportive care need domains thereby enhancing the understanding of the impacts of unmet SCNs. Findings may inform policy and practice change to improve supportive cancer care.

Mapping a decade of interventions to address the supportive care needs of individuals living with or beyond cancer: a scoping review of reviews.

PURPOSE: Individuals diagnosed with cancer have a range of supportive care needs that are often unmet despite substantial evidence supporting interventions to address them. Addressing this knowledge-translation gap represents a significant opportunity to improve health outcomes. A scoping review of reviews was conducted to map the breadth of evidence for interventions, highlighting those with an existing evidence base, as well as those requiring further research. METHODS: Systematic or meta-analytic reviews that examined interventions targeting supportive care needs of adults and children with cancer published between 2009 and 2019 were identified via searches in Medline, PsycINFO, CINAHL, Scopus and Cochrane. RESULTS: Five hundred fifty-one systematic reviews, including 250 meta-analyses, of interventions addressing supportive care needs, were included. Most reviews focused on interventions to address the physical and psychosocial needs of individuals with few reviews identified to address practical needs. Interventions using mental health therapies and physical activity were most commonly used to address all supportive care needs, followed by the use of pharmaceutical and medical devices, complementary and alternative therapies, information and education resources, dietary information and specific spirituality and return-to-work interventions. CONCLUSION: This scoping review of reviews presents the first broad overview of the literature addressing the supportive care needs of people living with or beyond cancer. It provides a database that health service providers can search to identify appropriate interventions. Results highlight specific research gaps, particularly for practical needs, where reviews are needed. It highlights where a substantial evidence base exists that researchers and policy-makers can consider when implementing interventions.

Are Estimates of the Health Opportunity Cost Being Used to Draw Conclusions in Published Cost-Effectiveness Analyses? A Scoping Review in Four Countries.

BACKGROUND: When healthcare budgets are exogenous, cost-effectiveness thresholds (CETs) used to inform funding decisions should represent the health opportunity cost (HOC) of such funding decisions, but HOC-based CET estimates have not been available until recently. In recent years, empirical HOC-based CETs for multiple countries have been published, but the use of these CETs in the cost-effectiveness analysis (CEA) literature has not been investigated. Analysis of the use of HOC-based CETs by researchers undertaking CEAs in countries with different decision-making contexts will provide valuable insights to further understand barriers and facilitators to the acceptance and use of HOC-based CETs. OBJECTIVES: We aimed to identify the CET values used to interpret the results of CEAs published in the scientific literature before and after the publication of jurisdiction-specific empirical HOC-based CETs in four countries. METHODS: We undertook a scoping review of CEAs published in Spain, Australia, the Netherlands and South Africa between 2016 (2014 in Spain) and 2020. CETs used before and after publication of HOC estimates were recorded. We conducted logit regressions exploring factors explaining the use of HOC values in identified studies and linear models exploring the association of the reported CET value with study characteristics and results. RESULTS: 1171 studies were included in this review (870 CEAs and 301 study protocols). HOC values were cited in 28% of CEAs in Spain and in 11% of studies conducted in Australia, but they were not referred to in CEAs undertaken in the Netherlands and South Africa. Regression analyses on Spanish and Australian studies indicate that more recent studies, studies without a conflict of interest and studies estimating an incremental cost-effectiveness ratio (ICER) below the HOC value were more likely to use the HOC as a threshold reference. In addition, we found a small but significant impact indicating that for every dollar increase in the estimated ICER, the reported CET increased by US$0.015. Based on the findings of our review, we discuss the potential factors that might explain the lack of adoption of HOC-based CETs in the empirical CEA literature. CONCLUSIONS: The adoption of HOC-based CETs by identified published CEAs has been uneven across the four analysed countries, most likely due to underlying differences in their decision-making processes. Our results also reinforce a previous finding indicating that CETs might be endogenously selected to fit authors' conclusions.

Empirical Estimates of the Marginal Cost of Health Produced by a Healthcare System: Methodological Considerations from Country-Level Estimates.

Many health technology assessment committees have an explicit or implicit reference value (often referred to as a 'threshold') below which new health technologies or interventions are considered value for money. The basis for these reference values is unclear but one argument is that it should be based on the health opportunity costs of funding decisions. Empirical estimates of the marginal cost per unit of health produced by a healthcare system have been proposed to capture the health opportunity costs of new funding decisions. Based on a systematic search, we identified eight studies that have sought to estimate a reference value through empirical estimation of the marginal cost per unit of health produced by a healthcare system for England, Spain, Australia, The Netherlands, Sweden, South Africa and China. We review these eight studies to provide an overview of the key methodological approaches taken to estimate the marginal cost per unit of health produced by the healthcare system with the aim to help inform future estimates for additional countries. The lead author for each of these papers was invited to contribute to the current paper to ensure all the key methodological issues encountered were appropriately captured. These included consideration of the key variables required and their measurement, accounting for endogeneity of spending to health outcomes, the inclusion of lagged spending, discounting and future costs, the use of analytical weights, level of disease aggregation, expected duration of health gains, and modelling approaches to estimating mortality and morbidity effects of health spending. Subsequent research estimates for additional countries should (1) carefully consider the specific context and data available, (2) clearly and transparently report the assumptions made and include stakeholder perspectives on their appropriateness and acceptability, and (3) assess the sensitivity of the preferred central estimate to these assumptions.

Pragmatic review of interventions to prevent inpatient hypoglycaemia.

AIMS: This pragmatic review aimed to map and summarize the literature on model of care interventions to prevent inpatient hypoglycaemia. Model of care interventions were broadly defined as interventions that either directly target the workforce or where implementation had a strong workforce effect. The review intended to provide information for decision-makers in local health care settings regarding potential interventions to prevent inpatient hypoglycaemia in their local context. METHODS: PubMed, Embase, CINAHL Plus and Scopus were systematically searched from 2009 to 2019 using key search terms for hypoglycaemia and hospital and evaluation. Included articles had to report an inpatient hypoglycaemia-related outcome. Interventions were categorized by intervention type and setting. Dysglycaemia outcomes were extracted (severe-hypoglycaemia, hypoglycaemia, hyperglycaemia and severe-hyperglycaemia). RESULTS: Forty-nine articles were included in the review. Interventions were categorized as: services (n = 8), role expansion (n = 6), education (n = 9), audit and feedback (n = 1), alerts and reminders (n = 3), protocol implementation methods (n = 1), order sets (n = 6), insulin charts (n = 1) and electronic glycaemic management systems (n = 14). Twenty-one articles reported on ICU-specific interventions, and 28 on interventions in non-ICU-specific settings. Study designs were predominantly non-randomized (n = 40). CONCLUSIONS: The review found positive evidence for a diverse range of evaluated interventions to prevent inpatient hypoglycaemia. Local decision-makers can use this review to identify interventions relevant to their local context. We suggest they evaluate those interventions using a decision analytic framework that combines the published evidence on effectiveness with local prevalence data to estimate the expected cost-effectiveness of the intervention options when implemented in their local context.

Are the benefits of new health services greater than their opportunity costs?

The Australian health system performs well compared with other developed countries, but there is potential for improved health outcomes through the consideration of the opportunity costs of funding new health services. The opportunity costs of funding a new health service are the benefits forgone from the activities that would be funded if the new health service was not funded. When the forgone activity cannot be observed directly, the expected opportunity costs have been estimated as the expected gain in quality-adjusted life years (QALYs) associated with marginal increases in government expenditure on health. We have previously estimated that a gain of 1 QALY is expected for every additional A$28033 of government expenditure on health. This paper discusses the relevance and proposed use of this estimate of opportunity costs to inform decisions around the public funding of new health services in Australia.

The political economy of the assessment of value of new health technologies.

Health technology assessment provides a common framework for evaluating the costs and benefits of new health technologies to inform decisions on the public funding of new pharmaceuticals and other health technologies. In Australia and England, empirical analyses of the opportunity costs of government spending on new health technologies suggest more quality adjusted life years are being forgone than are being gained by a non-trivial proportion of funded health technologies. This essay considers the relevance of available empirical estimates of opportunity costs and explores the relationship between the public funding of health technologies and broader political and economic factors. We conclude that the benefits of a general reduction in the prices paid by governments for new technologies outweigh the costs, but evidence of informed public acceptance of reduced access to new health technologies may be required to shift the current approach to assessing the value of new health technologies.

Estimating the Reference Incremental Cost-Effectiveness Ratio for the Australian Health System.

BACKGROUND: Spending on new healthcare technologies increases net population health when the benefits of a new technology are greater than their opportunity costs-the benefits of the best alternative use of the additional resources required to fund a new technology. OBJECTIVE: The objective of this study was to estimate the expected incremental cost per quality-adjusted life-year (QALY) gained of increased government health expenditure as an empirical estimate of the average opportunity costs of decisions to fund new health technologies. The estimated incremental cost-effectiveness ratio (ICER) is proposed as a reference ICER to inform value-based decision making in Australia. METHODS: Empirical top-down approaches were used to estimate the QALY effects of government health expenditure with respect to reduced mortality and morbidity. Instrumental variable two-stage least-squares regression was used to estimate the elasticity of mortality-related QALY losses to a marginal change in government health expenditure. Regression analysis of longitudinal survey data representative of the general population was used to isolate the effects of increased government health expenditure on morbidity-related, QALY gains. Clinical judgement informed the duration of health-related quality-of-life improvement from the annual increase in government health expenditure. RESULTS: The base-case reference ICER was estimated at AUD28,033 per QALY gained. Parametric uncertainty associated with the estimation of mortality- and morbidity-related QALYs generated a 95% confidence interval AUD20,758-37,667. CONCLUSION: Recent public summary documents suggest new technologies with ICERs above AUD40,000 per QALY gained are recommended for public funding. The empirical reference ICER reported in this article suggests more QALYs could be gained if resources were allocated to other forms of health spending.

Costs of paying higher prices for equivalent effects on the Pharmaceutical Benefits Scheme.

Objective The aims of the present study were to illustrate and discuss the effects of the non-maintenance of equivalent prices when the comparators of pharmaceuticals listed on the Pharmaceutical Benefits Schedule (PBS) on a cost-minimisation basis come off-patent and are subject to statutory price reductions, as well as further potential price reductions because of the effects of price disclosure. Methods Service use, benefits paid, and price data were analysed for a selected sample of pharmaceuticals recommended for listing on a cost-minimisation basis between 2008 and 2011, and their comparators, to estimate the cost savings to the PBS of maintaining equivalent prices. Results Potential cost savings for 12 pharmaceuticals, including alternative compounds and combination products across nine therapeutic groups, ranged from A$570000 to A$40million to April 2015. Potential savings increased significantly following recent amendments to the price disclosure process. Conclusions Potential savings from maintaining equivalent prices for all pharmaceuticals listed on the PBS on a cost-minimisation basis could be over A$500million per year. Actions to reduce these costs can be taken within existing policy frameworks, but legislative and political barriers may need to be addressed to minimise these costs, which are incurred by the taxpayer for no additional benefit. What is known about the topic? Pharmaceuticals listed on the PBS must provide value for money. Many pharmaceuticals achieve this by demonstrating equal effectiveness to an already listed pharmaceutical and requesting the same price as this comparator; that is, listing on a cost-minimisation basis. When the comparator moves off-patent, the price of the still-patented pharmaceutical is protected, whereas the off-patent drug is subject to price disclosure and often steep price reductions. What does this paper add? This paper adds to recent evidence on the costs to government of paying different prices for two or more pharmaceuticals that are equally effective. Between 2008 and 2011, the direct comparators for 68 pharmaceuticals listed on a cost-minimisation basis have moved onto the price disclosure list. Across 12 of these listings, the potential cost savings in the 10 months to April 2015 were A$73million. What are the implications for practitioners? The PBS costs the Australian government over A$9 billion per year. Annual savings over A$500million per year could be achieved by maintaining cost-minimisation across equally effective pharmaceuticals. This would improve the efficiency of the PBS at no risk to patients. Legislation is required to remove the existing F1 and F2 categorisation of listed pharmaceuticals, but the proposed changes would remove the need for therapeutic group premiums and simplify the pricing of PBS items.

Subjective well-being in older adults: folate and vitamin B12 independently predict positive affect.

Vitamin B12, folate and homocysteine have long been implicated in mental illness, and growing evidence suggests that they may play a role in positive mental health. Elucidation of these relationships is confounded due to the dependence of homocysteine on available levels of vitamin B12 and folate. Cross-sectional and longitudinal relationships between vitamin B12, folate, homocysteine and subjective well-being were assessed in a sample of 391 older, community-living adults without clinically diagnosed depression. Levels of vitamin B12, but not folate, influenced homocysteine levels 18 months later. Vitamin B12, folate and their interaction significantly predicted levels of positive affect (PA) 18 months later, but had no impact on the levels of negative affect or life satisfaction. Cross-sectional relationships between homocysteine and PA were completely attenuated in the longitudinal analyses, suggesting that the cross-sectional relationship is driven by the dependence of homocysteine on vitamin B12 and folate. This is the first study to offer some evidence of a causal link between levels of folate and vitamin B12 on PA in a large, non-clinical population.