Melbourne School of Population and Global Health - Research Publications

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    Optimizing Engagement in an Online Dietary Intervention for Depression (My Food & Mood Version 3.0): Cohort Study
    Young, CL ; Mohebbi, M ; Staudacher, HM ; Kay-Lambkin, F ; Berk, M ; Jacka, FN ; O'Neil, A (JMIR PUBLICATIONS, INC, 2021-03-31)
    BACKGROUND: Online interventions can be a cost-effective and efficient way to deliver programs to large numbers of people regardless of geographic location. However, attrition in web-based interventions is often an issue. Developing ways to keep participants engaged is important for ensuring validity and limiting potential biases. We developed a web-based dietary intervention as part of The My Food & Mood study which aimed to optimize ways to engage participants with low mood or depressive symptoms to promote dietary behavior change. Different versions of the My Food & Mood program were tested during optimization. Iterations were developed based on user feedback and usage analysis. OBJECTIVE: The purpose of this study was to compare engagement and nonusage attrition across 4 program iterations-which differed by platform format, delivery mode, and activity type-to create an optimized version. METHODS: Each program version contained modular videos with key activities with respect to implementing behavior change techniques of equivalent levels of required participation and length: version 1.0, desktop program and smartphone app; version 2.1, desktop or smartphone program; version 2.2, desktop program; and version 3.0, smartphone app. Adults with PHQ-8 scores of 5 or greater were recruited online and assigned to 1 of the 4 versions. Participants were asked to use the program for 8 weeks and complete measures at weeks 4 and 8. Engagement data were collected from the web-based platform system logs and customized reports. Cox regression survival analysis examined nonusage attrition and Kruskal-Wallis tests compared engagement across each cohort. RESULTS: A total of 614 adults participated. Kruskal-Wallis tests showed significant differences across the 4 cohorts in all engagement measures. The smartphone app (version 3.0) had the greatest engagement as measured by weeks engaged, total usage time, total time key activities, number of active sessions, percentage of activities completed against protocol, goals completed, and percentage of videos watched. Cox regression multivariate survival analysis showed referral from a health practitioner (hazard ratio [HR] 0.344, P=.001) and greater proficiency with computers (HR 0.796, P=.049) reduced the risk of nonusage attrition. Computer confidence was associated with an increased risk of nonusage attrition. CONCLUSIONS: My Food & Mood version 3.0, a dietary intervention delivered via smartphone app with self-monitoring tools for diet quality and mood monitoring, was the version with greatest engagement in a population with low mood or depression. The iterative design techniques employed and analysis of feedback from participants resulted in a program that achieved lower rates of nonusage attrition and higher rates of intensity of use.
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    The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?
    Morris, G ; Bortolasci, CC ; Puri, BK ; Marx, W ; O'Neil, A ; Athan, E ; Walder, K ; Berk, M ; Olive, L ; Carvalho, AF ; Maes, M (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2021-08)
    An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1β, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.
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    Gender Equality and Health in High-Income Countries: A Systematic Review of Within-Country Indicators of Gender Equality in Relation to Health Outcomes.
    Milner, A ; Kavanagh, A ; Scovelle, AJ ; O'Neil, A ; Kalb, G ; Hewitt, B ; King, TL (Mary Ann Liebert, 2021)
    Background: Gender equality is recognized as an important political, social, and economic goal in many countries around the world. At a country level, there is evidence that gender equality may have an important influence on health. Historically gender equality has mainly been measured to allow for between-country, rather than within-country comparisons; and the association between gender equality and health outcomes within countries has been under-researched. This article thus aimed to systematically review within-country indicators of gender equality in public health studies and assess the extent to which these are related to health outcomes. Materials and Methods: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach with two independent reviewers. Results: Data from the eight included studies revealed that there was heterogeneity in the way gender equality has been measured as a multidimensional construct. Associations between gender equality and a number of different health outcomes were apparent, including mortality, mental health, morbidity, alcohol consumption, and intimate partner violence, with gender equality mostly associated with better health outcomes. Conclusions: Further investigation into the effects of gender equality on health outcomes, including a clear conceptualization of terms, is critical for the development of policies and programs regarding gender equality.
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    Can endolysosomal deacidification and inhibition of autophagy prevent severe COVID-19?
    Morris, G ; Athan, E ; Walder, K ; Bortolasci, CC ; O'Neil, A ; Marx, W ; Berk, M ; Carvalho, AF ; Maes, M ; Puri, BK (PERGAMON-ELSEVIER SCIENCE LTD, 2020-12-01)
    The possibility is examined that immunomodulatory pharmacotherapy may be clinically useful in managing the pandemic coronavirus disease 2019 (COVID-19), known to result from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded RNA virus. The dominant route of cell entry of the coronavirus is via phagocytosis, with ensconcement in endosomes thereafter proceeding via the endosomal pathway, involving transfer from early (EEs) to late endosomes (LEs) and ultimately into lysosomes via endolysosomal fusion. EE to LE transportation is a rate-limiting step for coronaviruses. Hence inhibition or dysregulation of endosomal trafficking could potentially inhibit SARS-CoV-2 replication. Furthermore, the acidic luminal pH of the endolysosomal system is critical for the activity of numerous pH-sensitive hydrolytic enzymes. Golgi sub-compartments and Golgi-derived secretory vesicles also depend on being mildly acidic for optimal function and structure. Activation of endosomal toll-like receptors by viral RNA can upregulate inflammatory mediators and contribute to a systemic inflammatory cytokine storm, associated with a worsened clinical outcome in COVID-19. Such endosomal toll-like receptors could be inhibited by the use of pharmacological agents which increase endosomal pH, thereby reducing the activity of acid-dependent endosomal proteases required for their activity and/or assembly, leading to suppression of antigen-presenting cell activity, decreased autoantibody secretion, decreased nuclear factor-kappa B activity and decreased pro-inflammatory cytokine production. It is also noteworthy that SARS-CoV-2 inhibits autophagy, predisposing infected cells to apoptosis. It is therefore also suggested that further pharmacological inhibition of autophagy might encourage the apoptotic clearance of SARS-CoV-2-infected cells.
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    The impact of socioeconomic position (SEP) on women's health over the lifetime
    O'Neil, A ; Russell, JD ; Thompson, K ; Martinson, ML ; Peters, SAE (ELSEVIER IRELAND LTD, 2020-10)
    The "social gradient of health" refers to the steep inverse associations between socioeconomic position (SEP) and the risk of premature mortality and morbidity. In many societies, due to cultural and structural factors, women and girls have reduced access to the socioeconomic resources that ensure good health and wellbeing when compared with their male counterparts. Thus, the objective of this paper is to review how SEP - a construct at the heart of the Social Determinants of Health (SDoH) theory - shapes the health and longevity of women and girls at all stages of the lifespan. Using literature identified from PubMed, Cochrane, CINAHL and EMBASE databases, we first describe the SDoH theory. We then use examples from each stage of the life course to demonstrate how SEP can differentially shape girls' and women's health outcomes compared with boys' and men's, as well as between sub-groups of girls and women when other axes of inequalities are considered, including ethnicity, race and residential setting. We also explore the key consideration of whether conventional SEP markers are appropriate for understanding the social determinants of women's health. We conclude by making key recommendations in the context of clinical, research and policy development.
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    Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals
    O'Neil, A ; Nicholls, SJ ; Redfern, J ; Brown, A ; Hare, DL (ELSEVIER SCIENCE INC, 2020-07)
    BACKGROUND: The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. CHALLENGES: The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. PURPOSE: This commentary aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.
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    The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach
    Morris, G ; Bortolasci, CC ; Puri, BK ; Olive, L ; Marx, W ; O'Neil, A ; Athan, E ; Carvalho, AF ; Maes, M ; Walder, K ; Berk, M (PERGAMON-ELSEVIER SCIENCE LTD, 2020-10-01)
    In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.
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    Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement From the Cardiac Society of Australia and New Zealand (CSANZ)
    Nicholls, SJ ; Nelson, M ; Astley, C ; Briffa, T ; Brown, A ; Clark, R ; Colquhoun, D ; Gallagher, R ; Hare, DL ; Inglis, S ; Jelinek, M ; O'Neil, A ; Tirimacco, R ; Vale, M ; Redfern, J (ELSEVIER SCIENCE INC, 2020-07)
    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. CHALLENGES: The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. RECOMMENDATIONS: Every effort should be made to deliver safe, ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.
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    Sex differences in the association between diabetes and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a systematic review and meta-analysis of 5,162,654 participants
    Wang, Y ; O'Neil, A ; Jiao, Y ; Wang, L ; Huang, J ; Lan, Y ; Zhu, Y ; Yu, C (BMC, 2019-07-12)
    BACKGROUND: Studies have suggested sex differences in the mortality rate associated with diabetes. We conducted a meta-analysis to estimate the relative effect of diabetes on the risk of all-cause, cancer, cardiovascular disease (CVD), infectious disease, and respiratory disease mortality in women compared with men. METHODS: Studies published from their inception to April 1, 2018, identified through a systematic search of PubMed and EMBASE and review of references. We used the sex-specific RRs to derive the women-to-men ratio of RRs (RRR) and 95% CIs from each study. Subsequently, the RRR for each outcome was pooled with random-effects meta-analysis weighted by the inverse of the variances of the log RRRs. RESULTS: Forty-nine studies with 86 prospective cohorts met the inclusion criteria and were eligible for analysis. The pooled women-to-men RRR showed a 13% greater risk of all-cause mortality associated with diabetes in women than in men (RRR 1.13, 95% CI 1.07 to 1.19; P < 0.001). The pooled multiple-adjusted RRR indicated a 30% significantly greater excess risk of CVD mortality in women with diabetes compared with men (RRR 1.30, 95% CI 1.13 to 1.49; P < 0.001). Compared with men with diabetes, women with diabetes had a 58% greater risk of coronary heart disease (CHD) mortality, but only an 8% greater risk of stroke mortality (RRRCHD 1.58, 95% CI 1.32 to 1.90; P < 0.001; RRRstroke 1.08, 95% CI 1.01 to 1.15; P < 0.001). However, no sex differences were observed in pooled results of populations with or without diabetes for all-cancer (RRR 1.02, 95% CI 0.98 to 1.06; P = 0.21), infectious (RRR 1.13, 95% CI 0.90 to 1.38; P = 0.33), and respiratory mortality (RRR 1.08, 95% CI 0.95 to 1.23; P = 0.26). CONCLUSIONS: Compared with men with the same condition, women with diabetes have a 58% and 13% greater risk of CHD and all-cause mortality, respectively, although there was a significant heterogeneity between studies. This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention.
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    Gendered working environments as a determinant of mental health inequalities: a systematic review of 27 studies
    Milner, A ; Scovelle, AJ ; King, T ; Marck, C ; McAllister, A ; Kavanagh, A ; Shields, M ; Torok, E ; Maheen, H ; O'Neil, A (BMJ PUBLISHING GROUP, 2021-03)
    BACKGROUND: 'Gendered working environments' describes the ways in which (1) differential selection into work, (2) variations in employment arrangements and working hours, (3) differences in psychosocial exposures and (4) differential selection out of work may produce varied mental health outcomes for men and women. The aim of this study was to conduct a systematic review to understand gender differences in mental health outcomes in relation to the components of gendered working environments. METHODS: The review followed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search approach and focused on studies published in 2008-2018. The protocol for the review was prospectively registered with PROSPERO (CRD42019124066). FINDINGS: Across the 27 cohort studies included in the review, we found that (1) there was inconclusive evidence on the effect of occupational gender composition on the mental health of men and women, (2) women's mental health was more likely to be affected by long working hours than men's; however, precarious employment was more likely to be negatively associated with men's mental health, (3) exposure to traditional constructs of psychosocial job stressors negatively affected the mental health of both women and men, and (4) unemployment and retirement are associated with poorer mental health in both genders. INTERPRETATION: The findings from this review indicate that gendered working environments may affect the mental health of both men and women, but the association is dependent on the specific exposure examined. There is still much to be understood about gendered working environments, and future research into work and health should be considered with a gender lens.