Establishing multifactorial risk factors for adult-onset hearing loss: A systematic review with topic modelling and synthesis of epidemiological evidence.

BACKGROUND: This systematic review explores the multifaceted nature of risk factors contributing to adult-onset HL. The objective was to synthesise the most recent epidemiological evidence to generate pooled proportional incidences for the identified risk factors. METHODS: We conducted an extensive search of electronic databases (MEDLINE, EMBASE, and psychINFO) for studies providing epidemiological evidence of risk factors associated with hearing loss. Topic modelling using Latent Dirichlet Allocation (LDA) was first conducted to determine how many risk factor themes were available from the papers. Data were analysed by calculating the pooled proportional incidence using a meta-analysis of proportions. RESULTS: From the 72 studies reviewed, six key risk factor themes emerged through LDA topic modelling. The review identified ototoxicity, primarily caused by cancer treatments and antibiotics, infectious diseases like COVID-19, occupational noise exposure, lifestyle factors, health conditions, biological responses, and age progression as significant risk factors for HL. The highest proportional incidence was found with cancer-related ototoxicity at 55.4% (95%CI: 39.0-70.7), followed closely by ototoxicity from infectious diseases at 50.0% (95%CI: 28.5-71.5). This high proportional incidence suggests the need to explore less destructive therapies and proactively monitor hearing function during treatments. CONCLUSIONS: The findings of this review, combined with the synthesis of epidemiological evidence, enhance our understanding of hearing loss (HL) pathogenesis and highlight potential areas for intervention, thereby paving the way for more effective prevention and management of adult-onset hearing loss in our ageing global population.

The Benefits of Cochlear Implantation for Adults: A Systematic Umbrella Review.

OBJECTIVES: The uptake of cochlear implants among adults who could benefit (based on pure-tone audiometry) in developed countries is estimated to be less than 10%. Concerns about potential surgical complications, fear of losing residual hearing, and limited awareness about the benefits of this intervention contribute to the low adoption rate. To enhance quality of life and improve the uptake of cochlear implants, it is essential to have a clear understanding of their benefits. DESIGN: This umbrella review aims to summarize the major benefits of cochlear implant usage in adults, by synthesizing findings from published review articles. A comprehensive search of databases including MEDLINE, EMBASE, PsycINFO, and Google Scholar, was conducted. The search was limited to English-language review articles published between 1990 and 2022, focusing on cochlear implant outcomes in at least 5 adults (aged ≥18 years). Two independent reviewers screened titles, abstracts, and full-text articles, and conducted a quality assessment using the Joanna Briggs Checklist for Systematic Reviews and Research Syntheses. RESULTS: Forty-two articles were included in this review. There were 15 systematic reviews with meta-analysis, 25 systematic reviews without meta-analysis, and 2 systematic scoping reviews. All 42 articles underwent quality assessment using the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses, of which 40% (n = 17) satisfied 9 out of 11 quality criteria. This umbrella review shows that cochlear implants are associated with improvements in speech perception and recognition as well as improved quality of life and cognition. These benefits are observed in a significant proportion of adults undergoing the procedure, highlighting its effectiveness as a viable intervention for individuals with severe to profound hearing loss. CONCLUSIONS: The potential benefits of cochlear implantation appear to outweigh the risks and complications associated with the procedure. It is recommended that adults with severe to profound hearing loss in particular, engage in informed discussions with healthcare professionals to consider cochlear implantation as a viable treatment option.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) community survey: 1. population-based design, methodology and cohort profile.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe design and methods of Australian arm of International Spinal Cord Injury (Aus-InSCI) community survey, reporting on participation rates, potential non-response bias and cohort characteristics. SETTING: Survey of community-dwelling people with SCI at least 12 months post-injury, recruited between March 2018 and January 2019, from state-wide SCI services, a government insurance agency and not-for-profit consumer organisations across four Australian states. METHODS: The Aus-InSCI survey combined data for people with SCI from nine custodians, using secure data-linkage processes, to create a population-based, anonymised dataset. The Aus-InSCI questionnaire comprised 193 questions. Eligibility, response status and participation rates were calculated. Descriptive statistics depict participant characteristics. Logistic regression models were developed for probability of participation, and inverse probability weights generated to assess potential non-response bias. RESULTS: 1579 adults with SCI were recruited, a cooperation rate of 29.4%. Participants were predominantly male (73%), with 50% married. Mean age was 57 years (range 19-94) and average time post-injury 17 years (range 1-73). Paraplegia (61%) and incomplete lesions (68%) were most common. Males were more likely than females to have traumatic injuries (p < 0.0001) and complete lesions (p = 0.0002), and younger age-groups were more likely to have traumatic injuries and tetraplegia (p < 0.0001). Potential non-response bias evaluated using selected outcomes was found to be negligible in the Aus-InSCI cohort. CONCLUSIONS: The Aus-InSCI survey made efforts to maximise coverage, avoid recruitment bias and address non-response bias. The distributed, linked and coded (re-identifiable at each custodian level) 'virtual quasi-registry' data model supports systematic cross-sectional and longitudinal research.

COVID-19 and tinnitus: an initiative to improve tinnitus care.

OBJECTIVE: To investigate the effects of COVID-19 on individuals with tinnitus and their views to guide future tinnitus care. DESIGN: A mixed-methods cross-sectional research design. STUDY SAMPLE: An online survey was completed by 365 individuals with tinnitus from Australia and other countries. RESULTS: Tinnitus was reported to be more bothersome during the pandemic by 36% of respondents, whereas 59% reported no change and 5% reported less bothersome tinnitus. Nearly half of the respondents had received COVID-19 vaccination(s) and 12% of them reported more bothersome tinnitus while 2% developed tinnitus post-vaccination. Australian respondents spent less time in self-isolation or quarantine and saw fewer change in in-person social contact than respondents from other countries. More than 70% of respondents thought that tinnitus care services were insufficient both before and during the pandemic. Regarding their opinions on how to improve tinnitus care in the future, five themes including alleviation of condition, government policies, reduced barriers, self- and public-awareness, and hearing devices were identified. CONCLUSIONS: A majority of respondents did not perceive any change in tinnitus perception and one-third of respondents had worsened tinnitus during the pandemic. To improve tinnitus care, better awareness and more accessible resources and management are crucial.

Associations between intake of dietary flavonoids and the 10-year incidence of tinnitus in older adults.

PURPOSE: Dietary flavonoids are bioactive compounds that have been widely investigated for their associations with vascular health outcomes. As the development of tinnitus has been linked to vascular pathways, dietary flavonoids may have role in the prevention of tinnitus symptoms. This study reports the associations between the intakes of major classes of dietary flavonoids and 10-year incidence of tinnitus. METHODS: Of the 1753 participants (aged ≥ 50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and dietary intakes, 536 (31%) cases of tinnitus were identified and excluded from further analysis. Dietary data was collected using a semi-quantitative food frequency questionnaire and intakes of the five major classes of flavonoids were determined using U.S. Department of Agriculture flavonoid databases. Presence of prolonged tinnitus was assessed by a positive response to a single question administered by an audiologist. RESULTS: Of the remaining 1217 participants without tinnitus at baseline, 222 (18%) incident cases of tinnitus were identified over 10 years. After age-sex adjustment, participants in the third versus first quartile of proanthocyanidin intake were significantly less likely to develop incident tinnitus by 36% (HR = 0.64; 95% CI 0.43-0.96, Ptrend = 0.04). Following multivariable adjustment, this protective trend was non-significant (HR = 0.60; 95% CI 0.39-0.92; Ptrend = 0.06). Similarly, a non-significant protective trend was observed when comparing the fourth versus first quartile of intake of all flavonoids (OR = 0.61; 95% CI 0.39-0.96). No other associations were observed. CONCLUSION: Our findings do not support the hypothesis that dietary flavonoids are protective against the development of tinnitus over 10 years. The weak significant association observed between proanthocyanidin and incident tinnitus may be a chance finding as there was no significant trend following multivariate adjustments and, therefore, requires further studies to investigate these associations.

Health literacy and recovery following a non-catastrophic road traffic injury.

BACKGROUND: Health literacy (HL) is rarely addressed in rehabilitation research and practice but can play a substantial role in the recovery process after an injury. We aimed to identify factors associated with low HL and its relationship with 6-month health outcomes in individuals recovering from a non-catastrophic road traffic injury. METHODS: Four hundred ninety-three participants aged ≥17 years who had sustained a non-catastrophic injury in a land-transport crash, underwent a telephone-administered questionnaire. Information was obtained on socio-economic, pre-injury health and crash-related characteristics, and health outcomes (quality of life, pain related measures and psychological indices). Low HL was defined as scoring < 4 on either of the two scales of the Health Literacy Questionnaire that covered: ability to actively engage with healthcare providers ('Engagement' scale); and/or understanding health information well enough to know what to do ('Understanding' scale). RESULTS: Of the 493, 16.9 and 18.7% scored < 4 on the 'Understanding' and 'Engagement' scale (i.e. had low HL), respectively. Factors that were associated with low HL as assessed by both scales were: having pre-injury disability and psychological conditions; lodging a third-party insurance claim; experiencing overwhelming/great perceived sense of danger/death during the crash; type of road user; low levels of social satisfaction; higher pain severity; pain catastrophizing; and psychological- and trauma-related distress. Low HL (assessed by both scales) was associated with poorer recovery outcomes over 6 months. In these longitudinal analyses, the strongest association was with disability (p < 0.0001), and other significant associations were higher levels of catastrophizing (p = 0.01), pain severity (p = 0.04), psychological- (p ≤ 0.02) and trauma-related distress (p = 0.003), lower quality of life (p ≤ 0.03) and physical functioning (p ≤ 0.01). CONCLUSIONS: A wide spectrum of factors including claim status, pre-injury and psychological measures were associated with low HL in injured individuals. Our findings suggest that targeting low HL could help improve recovery outcomes after non-catastrophic injury.

Retinal Vasculature Fractal and Stroke Mortality.

BACKGROUND AND PURPOSE: Fractal analysis is a method of quantifying the branching complexity and density of the retinal vessels. We hypothesized that reduced fractal dimension, signifying a sparser vascular network, is associated with long-term stroke mortality. METHODS: We examined the relationship of fractal dimension and stroke mortality in a prospective, population-based cohort of 3143 participants aged 49 years or older. Fractal dimension was measured from digitized fundus photographs using a computer-automated method. Stroke mortality was documented from Australian National Death Index records. We defined reduced fractal dimension as values in the lowest quartile. RESULTS: Over 12 years, there were 132 (4.2%) stroke-related deaths. Stroke-related mortality was higher in participants with reduced fractal dimension (lowest quartile) compared with the highest quartile (7.7% versus 1.3%, P<0.01). After controlling for age, gender, smoking, blood pressure, history of stroke, and other factors, participants with reduced fractal dimension had higher stroke mortality (hazard ratio, 2.42 [95% CI, 1.15-5.07], lowest versus highest quartile). When modeled as a continuous variable, reduced fractal dimension was associated with increased stroke mortality (multivariable-adjusted hazard ratio, 1.26 [95% CI, 1.06-1.51], per SD decrease). CONCLUSIONS: Reduced retinal vascular fractal dimension is independently associated with 12-year stroke mortality. Reduced fractal dimension may indicate cerebral tissue hypoxia and increased risk of stroke.

A neuro-cardiac self-regulation therapy to improve autonomic and neural function after SCI: a randomized controlled trial protocol.

BACKGROUND: Spinal cord injury (SCI) is associated with autonomic imbalance and significant secondary conditions, including cardiac and brain dysfunction that adversely impact health and wellbeing. This study will investigate the effectiveness (intention-to-treat) of a neuro-cardiac self-regulation therapy to improve autonomic and neural/brain activity in adults with SCI living in the community. METHODS: A two-arm parallel, randomised controlled trial in which adults with SCI living in the community post-rehabilitation will be randomly assigned to a treatment or control group. The treatment group (N = 60) aged 18-70 years with a chronic traumatic or non-traumatic SCI, will receive intervention sessions once per week for 10 weeks, designed to regulate autonomic activity using computer-based feedback of heart rate variability and controlled breathing (called HRV-F). Comprehensive neurophysiological and psychological assessment will occur at baseline, immediate post-treatment, and 6 and 12-months post-treatment. Primary outcome measures include electrocardiography/heart rate variability (to assess autonomic nervous system function) and transcranial doppler sonography (to assess cerebral blood circulation in basal cerebral arteries). Secondary outcomes measures include continuous blood pressure, electroencephalography, functional near-infrared spectroscopy, respiration/breath rate, electrooculography, cognitive capacity, psychological status, pain, fatigue, sleep and quality of life. Controls (N = 60) will receive usual community care, reading material and a brief telephone call once per week for 10 weeks and be similarly assessed over the same time period as the HRV-F group. Linear mixed model analysis with repeated measures will determine effectiveness of HRV-F and latent class mixture modelling used to determine trajectories for primary and selected secondary outcomes of interest. DISCUSSION: Treatments for improving autonomic function after SCI are limited. It is therefore important to establish whether a neuro-cardiac self-regulation therapy can result in improved autonomic functioning post-SCI, as well as whether HRV-F is associated with better outcomes for secondary conditions such as cardiovascular health, cognitive capacity and mental health. TRIAL REGISTRATION: The study has been prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12621000870853 .aspx). Date of Registration: 6th July 2021. Trial Sponsor: The University of Sydney, NSW 2006. Protocol version: 22/07/2021.

Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration.

PURPOSE: To assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD). METHODS: 547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. Baseline dietary intake of flavonoids was determined using a validated food frequency questionnaire. At follow-up, presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements of central macular thickness (CMT) were recorded from optical coherence tomography scans. Visual acuity (VA) was documented using LogMAR charts. RESULTS: Participants in the first tertile of intake of the flavonol quercetin, and the flavan-3-ols epigallocatechin-3-gallate and epigallocatechin had significantly worse vision than participants in the third tertile-multivariable-adjusted least square (LS) mean VA: 14.68 vs. 19.53 (p = 0.04); 14.06 vs. 18.89 (p = 0.04); 13.86 vs. 18.86 (p = 0.03), respectively. Participants in the first compared to the third tertile of flavan-3-ol, epigallocatechin-3-gallate and epigallocatechin intake all had a twofold higher risk of IRF, multivariable-adjusted p trend of: 0.03, 0.01 and 0.02, respectively. The first vs. the third tertile of tea intake had significantly worse vision (LS mean VA: 13.49 vs. 19.04, p = 0.02), increased risk of IRF (OR 2.13, 95% CI 1.18-3.85) and greater mean CMT (279.59 µm vs. 256.52 µm, p = 0.04). CONCLUSIONS: Higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. Confirmation of these associations in interventional studies could result in promising new therapeutic approaches to the treatment of nAMD.

Comparison of physical and psychological health outcomes for motorcyclists and other road users after land transport crashes: an inception cohort study.

BACKGROUND: Serious injuries and fatalities among vulnerable road users on two wheeled motorised vehicles have increased across Australia and internationally in the past decade yet fallen for motor vehicle occupants. Almost half of all reported motorcycle injury crashes cause serious injury or death, nearly double that of motor vehicle police-reported crashes. This study explores associations with sociodemographic and pre-injury health characteristics and health outcomes after a road traffic injury; aiming to compare motorcyclists with other road users and inform recovery care. METHODS: An inception cohort study recruited 1854 individuals aged > 17 years, injured following land-transport crashes in New South Wales, Australia (July 2013-November 2016). Interviews conducted at baseline, 6-and 12-months post-injury elicited demographic, socioeconomic, and self-reported health conditions. RESULTS: Primary analysis involved 1854 participants who were recruited at baseline as three distinct road user groups; 628 (33.9%) motorcyclists, 927 (50%) vehicle occupants and 299 (16.1%) bicyclists. At baseline, injury patterns differed significantly between road user groups; motorcyclists were more than twice as likely to sustain lower extremity injury (p < 0.001); to have more severe injury severity scores (p < 0.001) and longer hospital stays versus vs vehicle occupants and bicyclists (< 0.001) across these measures. Injured motorcyclists were predominantly male (88.1%, p < 0.001), were younger on average (38 years) than bicyclists (41.5 years), had lower income and education levels, and poorer pre-injury physical health than other road user groups. Despite these differences, at 12 months post-injury motorcyclists had better physical health (SF12-PCS 2.07 (0.77, 3.36), p = 0.002) and reported lower pain scores (- 0.51 (- 0.83, - 0.2), p < 0.001) than vehicle occupants. Motorcyclists displayed less evidence of psychological distress than vehicle occupants, but more than bicyclists across several measures used. CONCLUSIONS: Road user types differ in important characteristics, including pre-injury health status and recovery after injury. As vulnerable road users experiencing transport crash and considering their higher initial injury severity, the degree of recovery among motorcyclists compared with other user types is remarkable and unexplained. Health and recovery outcomes after land-transport crashes is least favourable among vehicle occupants despite their higher levels of protection in a crash. This information is valuable for targeting early intervention strategies by road user type during the post-crash care phase, to improve long-term recovery.

Impacts of injury severity on long-term outcomes following motor vehicle crashes.

BACKGROUND: There is growing evidence that a range of pre-injury, injury related and post-injury factors influence social and health outcomes across the injury severity spectrum. This paper documents health related outcomes for people with mild, moderate and severe injury after motor vehicle crash (MVC) injuries in New South Wales, Australia. METHODS: This inception cohort study followed 2019 people injured in MVCs, for 6 and 12 months post-injury. We categorised moderate injury as hospital length-of-stay (LOS) of 2-6 days and Injury Severity Score (ISS) of 4-11, while severe injury as LOS ≥7 days or ISS ≥ 12. We examined differences in paid work status, 12-Item Short Form Survey (SF12), EQ-5D and World Health Organisation Disability Assessment Schedule II (WHODAS) outcomes longitudinally from baseline to 12 months between levels of injury severity using linear mixed models for repeated measures. We first considered minimally sufficient adjustment factors (age, sex, crash role, perceived danger in crash, pre-injury health, pre-injury EQ-5D, recruitment source), and then more extensive adjustments including post-injury factors. The presence of mediating pathways for SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) via post-injury factors was evaluated. RESULTS: Based on hospital length of stay (LOS), 25 and 10% of participants sustained moderate and severe injuries, respectively, while 43 and 4% had these injuries based on ISS. Twelve months post-injury LOS ≥7 days versus ≤1 day was associated with an estimated 9 units lower mean SF12 PCS using a minimally sufficient adjustment model, and LOS ≥ 7 days was associated with a 3 units lower mean SF12 MCS score. Mediation analyses (LOS ≥ 7 days vs ≤1 day) found for SF12 MCS outcomes, effects of injury severity were small and mostly indirect (direct effect - 0.03, indirect effect - 0.22). Whereas for SF12 PCS outcomes the effect of having a more severe injury rather than mild were both direct and indirect (direct effect - 0.50, indirect effect - 0.38). CONCLUSIONS: Individuals with severe injuries (those with LOS ≥ 7 days and ISS 12+) had poorer recovery 12 months after the injury. In addition, post-injury mediators have an important role in influencing long-term health outcomes. TRIAL REGISTRATION: Australia New Zealand Clinical trial registry identification number - ACTRN12613000889752 .

Perspectives of people with late age-related macular degeneration on mental health and mental wellbeing programmes: a qualitative study.

PURPOSE: People with age-related macular degeneration (AMD) experience high rates of depression, but rarely engage in or have access to tailored mental wellbeing programmes. This qualitative study investigated the perspectives of those primarily with late AMD on mental health and mental wellbeing programmes. METHODS: Twenty-eight people with late AMD in at least one eye, and one person with early AMD in both eyes, aged 56-87 years (mean age 78 years) attending a private eye clinic between December 2019 and January 2020 in Sydney, New South Wales, Australia, participated. Individual semi-structured interviews were conducted and analysed deductively using content analysis, following the individual level factors for health promotion interventions in the behaviour change wheel: Capability (Physical & Psychological), Opportunity (Physical & Social), and Motivation (Reflective & Automatic). RESULTS: Six major themes were identified: Capability: (1) Impact of vision loss on mobility and leisure pursuits; (2) Adjustment to living with vision loss; Opportunity: (3) Program considerations for those with AMD; (4) Stigma and self-perception of vision loss and mental health; Motivation: (5) Accumulation of vision-related issues as a barrier to participation; (6) Examples of others living with vision loss. General personal factors relevant to delivery of a programme in this age group were also identified: Comorbidities; Limitations using technology; Isolation; Financial concerns and Beliefs that undesired effects of aging are inevitable. CONCLUSIONS: Complex individual, environmental and social factors influence the perspectives of people with late AMD on mental health, and potential participation in mental wellbeing programmes. These factors should be considered when developing and implementing mental wellbeing programmes to improve the emotional and functional rehabilitation outcomes for people with AMD.

Evaluation of educational interventions on eye health for dietetic and pharmacy professions: a pre-post study.

BACKGROUND: We piloted an educational intervention that aimed to enhance awareness about nutrition-age-related macular degeneration (AMD) links among practising and student dietitians then expanded the scope of this intervention to include general eye health, which was delivered to pharmacy students. METHODS: A pilot intervention was conducted in 2019 at the Dietitians Australia Conference (Gold Coast, Australia) where practising and student dietitians underwent a 2-hour small group educational workshop on nutrition and AMD links. Pre-post questionnaires were administered to participants, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcome was a change in AMD-related nutrition knowledge pre-post intervention. A larger intervention was then conducted at the University of Sydney (Sydney, Australia) where pharmacy students underwent a 4-hour educational module to improve general eye health knowledge, as well as student perceptions and attitudes towards a pharmacists' role in low vision care. Similarly, pre-post questionnaires were administered, with voluntary completion of both questionnaires an indicator of consent to participate in the intervention. The primary intervention outcomes were changes in total knowledge, total perception and total attitude scores pre-post intervention. RESULTS: (1) Among 10 accredited and 5 student dietitians, there was significant overall knowledge improvement (mean pre-post score: 7.07 ± 1.94 vs. 10.8 ± 1.01, p = 0.001) specifically around appropriate dietary advice, food sources of key AMD-related nutrients, and awareness of supplements. (2) Among 179 second-year pharmacy students enrolled in the 'Pharmacy Practice' Unit of Study (Bachelor of Pharmacy, University of Sydney), total eye health knowledge (6.25 ± 1.93 vs. 6.64 ± 2.0; p = 0.011) significantly improved, along with total perception scores (41.54 ± 5.26 vs. 42.45 ± 4.95; p = 0.004). Total attitude scores were not significantly different. CONCLUSIONS: The pilot intervention improved relevant nutrition-AMD knowledge among practising/student dietitians. The modified intervention for pharmacy students also significantly improved general eye health knowledge as well as students' perception of a pharmacists' role in low vision care.

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol.

BACKGROUND: Studies report rates of mild cognitive impairment (MCI) in spinal cord injury (SCI) range between 10 and 60%. This broad estimate of MCI in SCI is most likely a result of: (i) inconsistent operationalization of MCI; (ii) heterogeneity among individuals with SCI; (iii) failure to account for MCI subtypes, thereby adding to the heterogeneity of samples; and, (iv) poor control for traumatic brain injury (TBI) that obscures differentiation of MCI attributable to TBI versus other factors. There is a paucity of longitudinal studies following the course of MCI in SCI, and none that account for multiple predictors of MCI, including interactions among predictors. METHODS: An inception cohort longitudinal study will assess approximately 100 individuals aged 17-80 years with acute SCI, with measures taken at three timepoints (baseline, 3 months post-baseline, and 12 months post-injury). Data relevant to medical care received within the first 24-48 h of presentation to the emergency department will be analysed, as will measures of cognition, injury characteristics, medical history, personal factors, psychological status, psychosocial functioning, and quality of life. Latent class mixture modelling will determine trajectories for the primary outcome of interest, cognitive functioning and its subtypes, and secondary outcomes of interest such as depression. Multiple regression analyses will identify predictors of MCI and its subtypes. DISCUSSION: The prospective design will reveal change in cognitive functioning across time and unveil different outcome trajectories; thus addressing the lack of knowledge on trajectories of MCI and MCI subtypes in SCI. Through subtyping MCI, we hope to yield groups of cognitively impaired individuals with SCI that are potentially more homogenous and thereby stable and predictable. This is the first study to capture emergency department and acute care diagnostic evidence of mild TBI, which has been poorly controlled in previous studies. Our study will also be the first to distinguish the contribution of TBI from other factors to the development of MCI in individuals with SCI. TRIAL REGISTRATION: The study was prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12619001702101 ) on 3rd December 2019.

Associations between dietary flavonoids and retinal microvasculature in older adults.

PURPOSE: In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. METHODS: Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model. RESULTS: The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; Ptrend = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; Ptrend = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; Ptrend = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; Ptrend = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1 µm narrower retinal venules (multivariable-adjusted P = 0.03). CONCLUSIONS: This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre.

Association of dietary nitrate intake with retinal microvascular structure in older adults.

PURPOSE: Existing research suggests that changes to retinal vascular caliber reflect nitric oxide (NO)-dependent endothelial dysfunction. Dietary nitrate is an important source of NO; however, studies on the link between dietary nitrate intake and retinal microvasculature are lacking. We aimed to assess the cross-sectional association between intake of dietary nitrate (from vegetable and non-vegetable sources) and retinal arteriolar and venular caliber among older adults. METHODS: Participants from the Blue Mountains Eye Study aged 49+ years with complete data at baseline on diet and retinal vessel measures were analyzed (n = 2813). Dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire. Nitrate intake from vegetable and non-vegetable sources was estimated using a validated comprehensive database and other published data where necessary. Fundus photographs were taken and retinal vascular caliber measured using validated computer-assisted techniques and summarized. RESULTS: Participants in the lowest versus highest tertile of vegetable nitrate intake had significantly narrower retinal arterioles: 186.2 ± 0.48 versus 187.6 ± 0.48 µm (multivariable-adjusted p = 0.04). After multivariable adjustment, each 10-unit higher intake of total nitrate and vegetable nitrate was associated with 0.089 ± 0.004 and 0.090 ± 0.004 µm wider retinal arteriolar caliber, respectively, both p = 0.03. Each 10-unit higher vegetable nitrate intake was associated with 0.092 ± 0.005 µm narrower retinal venules (p = 0.05). CONCLUSION: Intake of dietary nitrate, particularly from vegetable sources, was associated with beneficial variations in both retinal arteriolar and venular caliber among older adults. Further research into associations between dietary nitrate and the retinal microvasculature could allow for greater understanding and possible prevention of clinical cardiovascular events.

Dietary zinc intake is associated with macular fluid in neovascular age-related macular degeneration.

IMPORTANCE: Numerous dietary factors have been shown to reduce progression from early to late age-related macular degeneration (AMD), however, little is known on their impact in patients diagnosed with late-stage disease. BACKGROUND: To determine whether a dietary intake high in antioxidants and zinc, fruits, vegetables and fish is associated with favourable clinical outcomes in patients with neovascular AMD (nAMD) undergoing anti-vascular endothelial growth factor therapy. DESIGN: Cross-sectional study carried out at a private ophthalmology clinic. PARTICIPANTS: Five hundred forty-seven participants with nAMD. METHODS: Diet was determined using a validated food frequency questionnaire. Presence of intra-retinal and sub-retinal fluid (IRF, SRF), pigment epithelial detachment and central macular thickness (CMT) were recorded from ocular coherence tomography images. MAIN OUTCOME MEASURES: Fluid presence, mean CMT and visual acuity. RESULTS: Participants with daily zinc intake below (n = 91) vs above (n = 333) 8.1 mg had greater odds of SRF being present, multivariable-adjusted odds ratio (OR) of 0.56 (95% CI 0.36-0.96). This association was stronger in persons with at least 6 months of treatment, OR of 0.32 (95% CI 0.14-0.75). In the entire cohort, participants in the lowest or first quartile compared to those in the upper three quartiles of zinc intake combined had significantly greater mean CMT (254.81 µm vs 232.15 µm, respectively, multivariable-adjusted P = .03). CONCLUSIONS AND RELEVANCE: Low dietary zinc intake was associated with a greater likelihood of SRF presence, particularly in those treated for at least 6 months, and increased macular thickness in treated eyes with nAMD.

Age-related macular degeneration.

Age-related macular degeneration is a leading cause of visual impairment and severe vision loss. Clinically, it is classified as early-stage (medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic). Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids). Progression from early-stage to late-stage disease can be slowed with high-dose zinc and antioxidant vitamin supplements. Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab, aflibercept, or bevacizumab) is highly effective at treating neovascular age-related macular degeneration, and has markedly decreased the prevalence of visual impairment in populations worldwide. Currently, no proven therapies for atrophic disease are available, but several agents are being investigated in clinical trials. Future progress is likely to be from improved efforts in prevention and risk-factor modification, personalised medicine targeting specific pathways, newer anti-vascular endothelial growth factor agents or other agents, and regenerative therapies.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Carbohydrate nutrition variables and risk of disability in instrumental activities of daily living.

PURPOSE: We aimed to examine the prospective association between dietary glycemic index (GI) and glycemic load (GL) of foods consumed, intakes of carbohydrates and fiber, and the ability to perform activities of daily living (ADL) in older adults. METHODS: A total of 844 participants from the Blue Mountains Eye Study aged 60 years or older were examined from 2002-2004 to 2007-2009. Dietary information was collected using a validated, semi-quantitative food-frequency questionnaire. The Older Americans Resources and Services activities of daily living scale were administered to assess the functional status of participants. Multivariable logistic regression analysis was performed. RESULTS: After multivariable adjustment, participants who were in the second and third quartiles of energy-adjusted total fiber intake compared to those in the first quartile of intake (reference group) at baseline had reduced risk of incident impaired instrumental activities of daily living (IADL) 5 years later: OR, 0.39 (95% CI 0.22-0.70) and OR 0.54 (95% CI 0.30-0.95), respectively. Analyses that involved dichotomized total fiber intake showed that participants in the upper three quartiles of total fiber intake (> 19 g/day), compared to those in the lowest quartile of intake (≤ 19 g/day) or reference group, had reduced IADL disability risk 5 years later: OR 0.49 (95% CI 0.31-0.79). Non-significant associations were observed with total carbohydrates, GI, and GL and with risk of impaired total and basic ADL at 5-year follow-up. CONCLUSIONS: Habitual fiber consumption might be beneficial in leading to improved health status subserving performance of instrumental daily activities, needed to function in the community.