Childhood Social Isolation as a Predictor of Retinal Neuronal Thickness in Middle Age: A Lifecourse Birth Cohort Study.

OBJECTIVE: We investigated whether childhood social isolation was associated with retinal neural layer changes in adulthood, and whether this association was independent of other childhood or adulthood risk factors, including adult social isolation. METHODS: Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal population-based birth cohort from Aotearoa New Zealand ( n = 1037), born 1972 to 1973 and followed until age 45 years, with 94% of the living cohort still participating. Social isolation was recorded prospectively at ages 5, 7, 9, and 11 years, from teacher and parent report. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer thicknesses were measured via optical coherence tomography at age 45 years. RESULTS: Childhood social isolation was associated with thinner average RNFL ( B = -0.739, p = .02), nasal RNFL ( B = -1.118, p = .005), and inferior RNFL ( B = -1.524, p = .007), although only nasal RNFL remained significant after adjustment. These associations were not fully explained by other psychosocial or physical health risk factors in childhood or adulthood, nor were they mediated by adult loneliness or social support. CONCLUSIONS: Childhood social isolation was an independent predictor of RNFL thickness in middle age. Highlighting prospective links between childhood psychosocial adversity and retinal neuronal measures will help to inform future research into the utility of retinal neuronal thickness as a biomarker for neurodegeneration.

Genotypic and phenotypic characterisation of RP2- and RPGR-associated X-linked inherited retinal dystrophy, including female manifestations.

BACKGROUND: With the promise of gene replacement therapy, eligible males and females with X-linked inherited retinal dystrophy (XL-IRD) should be identified. METHODS: Retrospective observational cohort study to establish the phenotypic and genotypic spectrum of XL-IRD within New Zealand (NZ). Thirty-two probands, including 9 females, with molecularly proven XL-IRD due to RP2 or RPGR mutations, and 72 family members, of which 43 were affected, were identified from the NZ IRD Database. Comprehensive ophthalmic phenotyping, familial cosegregation, genotyping, and bioinformatics were undertaken. Main outcome measures were: RP2 and RPGR pathogenic variant spectrum, phenotype in males and females (symptoms, age of onset, visual acuity, refraction, electrophysiology, autofluorescence, retinal appearance), and genotype-phenotype correlation. RESULTS: For 32 families, 26 unique pathogenic variants were identified; in RP2 (n = 6, 21.9% of all families), RPGR exons 1-14 (n = 10, 43.75%), and RPGR-ORF15 (n = 10, 34.3%). Three RP2 and 8 RPGR exons 1-14 variants are novel, rare, and cosegregate. Thirty-one percent of carrier females were significantly affected, with 18.5% of families initially classified as autosomal dominant. Of five Polynesian families, 80% had novel disease-causing variants. One Maori family showed keratoconus segregating with an ORF15 variant. CONCLUSIONS: Significant disease was present in 31% of genetically proven female carriers, often leading to an erroneous presumption of the inheritance pattern. Pathogenic variants in 44% of the families were in exon 1-14 of RPGR, more frequent than usually described, which may inform the gene testing algorithm. Proving cosegregation in families for novel variants and identifying affected females and males translates to optimised clinical care and potential for gene therapy.

Advance care plans in UK care home residents: a service evaluation using a stepped wedge design.

INTRODUCTION: advance care planning (ACP) in care homes has high acceptance, increases the proportion of residents dying in place and reduces hospital admissions in research. We investigated whether ACP had similar outcomes when introduced during real-world service implementation. METHODS: a service undertaking ACP in Lincoln, UK care homes was evaluated using routine data. Outcomes were proportion of care homes and residents participating in ACP; characteristics of residents choosing/declining ACP and place of death for those with/without ACP. Hospital admissions were analysed using mixed-effects Poisson regression for number of admissions, and a mixed-effects negative binomial model for number of occupied hospital bed days. RESULTS: About 15/24 (63%) eligible homes supported the service, in which 404/508 (79.5%) participants chose ACP. Residents choosing ACP were older, frailer, more cognitively impaired and malnourished; 384/404 (95%) residents choosing ACP recorded their care home as their preferred place of death: 380/404 (94%) declined cardiopulmonary resuscitation. Among deceased residents, 219/248 (88%) and 33/49 (67%) with and without advance care plan respectively died in their care home (relative risk 1.35, 95% confidence interval [CI] 1.1-1.6, P < 0.001). Hospital admission rates and bed occupancy did not differ after implementation. DISCUSSION: About 79.5% participants chose ACP. Those doing so were more likely to die at home. Many homes were unwilling or unable to support the service. Hospital admissions were not reduced. Further research should consider how to enlist the support of all homes and to explore why hospital admissions were not reduced.

Prospective observational study of respiratory Aspergillus colonization or disease in patients with various stages of chronic obstructive pulmonary disease utilizing culture versus nonculture techniques.

Chronic obstructive pulmonary disease (COPD) patients have been recognized to be at increased risk of Aspergillus spp. colonization, which may progress to invasive pulmonary aspergillosis (IPA). The objective of this study was to determine the frequency of Aspergillus colonization, or disease, in a cohort of COPD patients. A prospective observational study was undertaken to determine Aspergillus colonization, or disease, in consecutive COPD patients undergoing bronchoscopy. Fungal culture as well as galactomannan antigen (GM) and Aspergillus nucleic acid detection (PCR) were performed on bronchoalveolar lavage fluid (BAL) samples. One hundred and fifty patients were recruited. One hundred and twelve (74.7%) were outpatients, 38 (25.33%) were inpatients, of whom 6 (4%) were in the intensive care unit. Most patients (N = 122, 81.3%) were either COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 1 or 2. Nine (6%) patients were on systemic steroids, 64 (42.7%) on inhaled steroids, and 9 (6%) on both. Seventeen patients (11.3%) had at least one positive test for Aspergillus detection (culture ± galactomannan ± polymerase chain reaction [PCR]), 13 (76.4%) of whom were COPD GOLD stages 1 or 2.  Five patients had probable or putative IPA. Aspergillus sp. was detected in five patients (3.3%) by culture, but detection increased to 17 (11.3%) by the additional testing for GM or Aspergillus DNA. The frequency of Aspergillus detection in this cohort of COPD patients may reflect the predominance of early GOLD stages among the study population but deserves further investigation to determine its relevance as a predictive risk factor for IPA. LAY SUMMARY: COPD is a risk factor for Aspergillus spp. colonization. Bronchoalveolar lavage samples of 150 COPD patients were tested for presence of Aspergillus fumigatus, which was detected in five patients (3.3%) by culture, but detection of Aspergillus increased to 17 (11.3%) by additional GM and PCR testing.

Cataract surgery for falls prevention and improving vision: modelling the health gain, health system costs and cost-effectiveness in a high-income country.

AIM: To estimate the health gain, health system costs and cost-effectiveness of cataract surgery when expedited as a falls prevention strategy (reducing the waiting time for surgery by 12 months) and as a routine procedure. METHODS: An established injurious falls model designed for the New Zealand (NZ) population (aged 65+ years) was adapted. Key parameters relating to cataracts were sourced from the literature and the NZ Ministry of Health. A health system perspective with discounting at 3% was used. RESULTS: Expedited cataract surgery for 1 year of incident cases was found to generate a total 240 quality-adjusted life years (QALYs) (95% uncertainty interval (UI) 161 to 360) at net health system costs of NZ$2.43 million (95% UI 2.02 to 2.82 million) over the remaining lifetimes of the surgery group. This intervention was cost-effective by widely accepted standards with an incremental cost-effectiveness ratio (ICER) of NZ$10 600 (US$7540) (95% UI NZ$6030 to NZ$15 700) per QALY gained. The level of cost-effectiveness did not vary greatly by sex, ethnicity and previous fall history, but was higher for the 65-69 age group compared with the oldest age group of 85-89 years (NZ$7000 vs NZ$14 200 per QALY gained). Comparing cataract surgery with no surgery, the ICER was even more favourable at NZ$4380 (95% UI 2410 to 7210) per QALY. Considering only the benefits for vision improvement and excluding the benefits of falls prevention, it was still favourable at NZ$9870 per QALY. CONCLUSIONS: Expedited cataract surgery appears very cost-effective. Routine cataract surgery is itself very cost-effective, and its value appears largely driven by the falls prevention benefits.

Proof-of-concept calculations to determine the health-adjusted life-year trade-off between intravitreal anti-VEGF injections and transmission of COVID-19.

BACKGROUND: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. METHOD: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. RESULTS: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). CONCLUSION: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.

The Role of Virtual Reality in Improving Health Outcomes for Community-Dwelling Older Adults: Systematic Review.

BACKGROUND: Virtual reality (VR) delivered through immersive headsets creates an opportunity to deliver interventions to improve physical, mental, and psychosocial health outcomes. VR app studies with older adults have primarily focused on rehabilitation and physical function including gait, balance, fall prevention, pain management, and cognition. Several systematic reviews have previously been conducted, but much of the extant literature is focused on rehabilitation or other institutional settings, and little is known about the effectiveness of VR apps using immersive headsets to target health outcomes among community-dwelling older adults. OBJECTIVE: The objective of this review was to evaluate the effectiveness of VR apps delivered using commercially available immersive headsets to improve physical, mental, or psychosocial health outcomes in community-dwelling older adults. METHODS: Peer-reviewed publications that included community-dwelling older adults aged ≥60 years residing in residential aged care settings and nursing homes were included. This systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for systematic reviews of effectiveness evidence. The title of this review was registered with JBI, and the systematic review protocol was registered with the International Prospective Register of Systematic Reviews. RESULTS: In total, 7 studies that specifically included community-dwelling older adults were included in this review. VR apps using a head-mounted display led to improvements in a number of health outcomes, including pain management, posture, cognitive functioning specifically related to Alzheimer disease, and a decreased risk of falls. A total of 6 studies reported a statistically significant difference post VR intervention, and 1 study reported an improvement in cognitive function to reduce navigational errors. Only one study reported on the usability and acceptability of the interventions delivered through VR. While one study used a distraction mechanism for pain management, none of the studies used gaming technology to promote enjoyment. CONCLUSIONS: Interventions to improve health outcomes through VR have demonstrated potential; however, the ability to synthesize findings by primary outcome for the older adult population is not possible. A number of factors, especially related to frailty, usability, and acceptability, also need to be explored before more substantial recommendations on the effectiveness of VR interventions for older adults can be made. TRIAL REGISTRATION: PROSPERO CRD42019143504; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=143504.

Diabetic retinopathy screening using deep neural network.

IMPORTANCE: There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. BACKGROUND: To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. DESIGN: Retrospective audit. PARTICIPANTS: Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. METHODS: Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve, sensitivity and specificity. RESULTS: For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. CONCLUSIONS AND RELEVANCE: This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema.

Is the Tunnel Technique More Effective Than Open Augmentation With a Titanium-Reinforced Polytetrafluoroethylene Membrane for Horizontal Ridge Augmentation?

PURPOSE: Studies have shown that horizontal ridge augmentation with a nonresorbable membrane is subject to a relatively frequent occurrence of dehiscence and loss of the graft. This study was designed to compare the outcomes of a tunnel technique versus an open technique using a titanium-reinforced polytetrafluoroethylene (PTFE) membrane. MATERIALS AND METHODS: A retrospective cohort study, in which the data were collected by chart review, was designed to compare patients who had undergone horizontal ridge augmentation with a 1:1 ratio of mineralized freeze-dried allograft and particulate bovine hydroxyapatite by the tunnel technique with patients who had undergone an open technique with a titanium-reinforced PTFE membrane. The incidence of wound dehiscence or membrane exposure, the number of postoperative visits required, and the number of systemic antibiotic courses needed, as well as the number of grafted sites that subsequently were amenable to routine implant placement after graft maturation, were compared between the 2 techniques. The differences in implants placed between the 2 methods were analyzed with the Fisher exact test. The secondary hypothesis (regarding wound dehiscence, number of postoperative visits, and number of systemic antibiotic courses) was analyzed by Poisson regression. RESULTS: The chart review found 52 patients, with 21 treated by the tunnel technique and 31 treated with the open technique. Within 6 months after bone grafting, 18 patients (86%) treated with tunnel technique grafts received dental implants whereas 22 patients (71%) treated with the open technique received dental implants. Dehiscence developed in a greater proportion of ridge augmentations with the PTFE method (52% vs 19%). There was a trend toward an increased number of courses of antibiotics prescribed for this group (P = .11), as well as a significant increase in the number of postoperative visits required (P = .003). CONCLUSIONS: For horizontal defects amenable to either technique, the findings of this study show the tunnel technique is a more cost-effective option with similar success to the open technique.

Use of Transalveolar Sutures in Conjunction With Grafting to Preserve Vestibular Depth and Augment Gingival Thickness Around Mandibular Implants.

Preservation or reconstruction of the soft tissues around dental implants is an essential component of implant dentistry. Increased width and thickness of the keratinized tissue surrounding dental implants has been recognized as an important factor associated with long-term implant success. When extractions and ridge reduction are performed concurrently with implant placement, maintaining vestibular depth also is of utmost importance. A previous report described a technique for applying bone-anchoring sutures to preserve keratinized tissue and vestibular depth around implants. The present report describes a variation of the procedure for the simultaneous correction of situations in which the existing keratinized tissue is thin and narrow and preserving and apically positioning it might not provide an appropriate gingival cuff.

Update and projections for New Zealand's ophthalmology workforce.

AIM: The aim of this study was to update and project the growth of ophthalmologists in New Zealand. This will help decision makers better understand the current ophthalmologist workforce and make appropriate resource allocations. METHOD: Supply and demographics of ophthalmologists in New Zealand were obtained from the Medical Council of New Zealand, Health Workforce New Zealand and Health New Zealand - Te Whatu Ora. Ophthalmology trainee numbers were extracted from the annual reports of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO). New Zealand population statistics were extracted from the Stats NZ database. A simulation model was developed to project the growth of ophthalmologists from 2024 to 2050. RESULTS: In March 2023, there were 175 practising ophthalmologists in New Zealand. Overall, there were 34.0 ophthalmologists per million population, with 201.4 ophthalmologists per million for those aged ≥65 years. To maintain the current ratio, an additional 20 practising ophthalmologists are needed by 2050. CONCLUSION: The ratio of ophthalmologists per million population aged ≥65 years is projected to drop by 1.5% annually. To meet the demand of an increasing and ageing population, and RANZCO's goal of 40 ophthalmologists per million population, there needs to be an increase in ophthalmologist training positions from the current 5-year average of 6.6 to 11 new trainees annually, and a more effective distribution of the ophthalmologist workforce.

Changes in quality of life scores with intravenous immunoglobulin or plasmapheresis in patients with myasthenia gravis.

BACKGROUND: Intravenous immunoglobulin (IVIG) and plasmapheresis (plasma exchange (PLEX)) have comparable efficacy in reducing the Quantitative Myasthenia Gravis Score for disease severity (QMGS) in patients with moderate to severe myasthenia gravis (MG). OBJECTIVE: To determine if the improvement in the quality of life (QOL) after immunomodulation is comparable with either IVIG or PLEX. METHODS: 62 patients participated in the MG-QOL-60 study, completing the questionnaire at baseline and at day 14 after treatment. The MG-QOL-15 scores were computed from the MG-QOL-60 questionnaire responses. We analysed the change in the QOL scores from baseline to day 14 in both treatment groups. RESULTS: The scores in both QOL scales decreased at day 14 in the IVIG and PLEX groups, without significant difference between groups (QOL-15: IVIG -5.7 ± 8.5, PLEX: -7.0 ± 7.6, p=0.52; QOL-60: IVIG -13.3 ± 16.9, PLEX -18.5 ± 22.0, p = 0.41). The improvement in QOL showed a good correlation with the decrease in QMGS. There was an excellent correlation between the MG-QOL-15 and MG-QOL-60 scores at baseline and at day 14. CONCLUSIONS: This study of MG-QOL changes supports recent findings that IVIG and PLEX are comparable in the treatment of patients with moderate to severe MG and worsening symptoms. Furthermore, our study supports the use of the MG-QOL-15 as a secondary outcome measure in future clinical trials in MG.

Does amblyopia have a functional impact? Findings from the Dunedin Multidisciplinary Health and Development Study.

BACKGROUND: Existing data on the functional impact of amblyopia are conflicting. The functional impact of amblyopia is a critical component of the viability and effectiveness of childhood vision screening programmes and treatment regimes. DESIGN: Prospective longitudinal birth cohort (the Dunedin Multidisciplinary Health and Development Study). PARTICIPANTS: One thousand thirty-seven children born in Dunedin, New Zealand, between April 1972 and March 1973, assessed from ages 3 to 32 years. METHODS: Comparison of study members with no amblyopia, recovered amblyopia, possible amblyopia or amblyopia according to both classic (6/12 visual acuity or worse in at least one eye, or a two-line or greater differential between the visual acuity in both eyes) and modern (6/9 visual acuity or worse in at least one eye) definitions of amblyopia. MAIN OUTCOME MEASURES: Childhood motor development, teenage self-esteem and adult socioeconomic status (assessed by occupation, education, reading ability and income). RESULTS: There was no evidence of poorer motor development, lower self-esteem or reduced adult socioeconomic status in study members with amblyopia or recovered amblyopia when compared with those with no amblyopia. CONCLUSIONS: Amblyopia or having recovered amblyopia does not functionally impact on childhood motor development, teenage self-esteem or adult socioeconomic status within this cohort. The wide range of visual deficits and adaptations that are known to occur in amblyopic vision do not translate into important 'real life' outcomes for the study members with amblyopia or recovered amblyopia. The age-related cumulative lifetime risk of bilateral visual impairment in amblyopia will be assessed in future studies.

A Lack of Restraint: Comparing Virtual Reality Interaction Techniques for Constrained Transport Seating.

Standalone Virtual Reality (VR) headsets can be used when travelling in cars, trains and planes. However, the constrained spaces around transport seating can leave users with little physical space in which to interact using their hands or controllers, and can increase the risk of invading other passengers' personal space or hitting nearby objects and surfaces. This hinders transport VR users from using most commercial VR applications, which are designed for unobstructed 1-2m 360 ° home spaces. In this paper, we investigated whether three at-a-distance interaction techniques from the literature could be adapted to support common commercial VR movement inputs and so equalise the interaction capabilities of at-home and on-transport users: Linear Gain, Gaze-Supported Remote Hand, and AlphaCursor. First, we analysed commercial VR experiences to identify the most common movement inputs so that we could create gamified tasks based on them. We then investigated how well each technique could support these inputs from a constrained 50x50cm space (representative of an economy plane seat) through a user study (N=16), where participants played all three games with each technique. We measured task performance, unsafe movements (play boundary violations, total arm movement) and subjective experience and compared results to a control 'at-home' condition (with unconstrained movement) to determine how similar performance and experience were. Results showed that Linear Gain was the best technique, with similar performance and user experience to the 'at-home' condition, albeit at the expense of a high number of boundary violations and large arm movements. In contrast, AlphaCursor kept users within bounds and minimised arm movement, but suffered from poorer performance and experience. Based on the results, we provide eight guidelines for the use of, and research into, at-a-distance techniques and constrained spaces.

Are macular drusen in midlife a marker of accelerated biological ageing?

CLINICAL RELEVANCE: Macular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing. BACKGROUND: Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife - a sign of the earliest stages of age-related macular degeneration (AMD) - are associated with accelerated biological ageing more generally. METHODS: Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years. RESULTS: Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen. CONCLUSIONS: In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.

Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort.

Purpose: The retina has potential as a biomarker of brain health and Alzheimer's disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort. Participants and Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI). Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities. Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.

Roadmap for an imaging and modelling paediatric study in rural NZ.

Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child. We have pilot tested an imaging protocol to be minimally disruptive to the children and demonstrated state-of-the-art image processing and personalized computational models using the imaging data. Our imaging protocol spans brain, lungs, heart, muscle, bones, abdominal and vascular systems. Our initial set of results demonstrated child-specific measurements on one dataset. This work is novel and interesting as we have run multiple computational physiology workflows to generate personalized computational models. Our proposed work is the first step towards achieving the integration of imaging and modelling improving our understanding of the human body in paediatric health and disease.

Ninety-Day Stroke or Transient Ischemic Attack Recurrence in Patients Prescribed Anticoagulation in the Emergency Department With Atrial Fibrillation and a New Transient Ischemic Attack or Minor Stroke.

Background For patients with atrial fibrillation seen in the emergency department (ED) following a transient ischemic attack (TIA) or minor stroke, the impact of initiating oral anticoagulation immediately rather than deferring the decision to outpatient follow-up is unknown. Methods and Results We conducted a planned secondary data analysis of a prospective cohort of 11 507 adults in 13 Canadian EDs between 2006 and 2018. Patients were eligible if they were aged 18 years or older, with a final diagnosis of TIA or minor stroke with previously documented or newly diagnosed atrial fibrillation. The primary outcome was subsequent stroke, recurrent TIA, or all-cause mortality within 90 days of the index TIA diagnosis. Secondary outcomes included stroke, recurrent TIA, or death and rates of major bleeding. Of 11 507 subjects with TIA/minor stroke, atrial fibrillation was identified in 11.2% (1286, mean age, 77.3 [SD 11.1] years, 52.4% male). Over half (699; 54.4%) were already taking anticoagulation, 89 (6.9%) were newly prescribed anticoagulation in the ED. By 90 days, 4.0% of the atrial fibrillation cohort had experienced a subsequent stroke, 6.5% subsequent TIA, and 2.6% died. Results of a multivariable logistic regression indicate no association between prescribed anticoagulation in the ED and these 90-day outcomes (composite odds ratio, 1.37 [95% CI, 0.74-2.52]). Major bleeding was found in 5 patients, none of whom were in the ED-initiated anticoagulation group. Conclusions Initiating oral anticoagulation in the ED following new TIA was not associated with lower recurrence rates of neurovascular events or all-cause mortality in patients with atrial fibrillation.