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BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHOD(S): The Tasmanian Study of Cognition and Gait (TASCOG) was a population based longitudinal cohort study with data collected at three phases from 2005 to 2012. Participants aged 60-85, were randomly selected from the electoral roll. Various data were used to operationalize a 36-item Frailty Index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex and education. RESULT(S): A total of 385 participants were included at baseline. The mean age was 72.5 years (SD 7.0), 44% were female (n=171). In fully adjusted linear mixed models, frailty (FI x time beta -0.001, 95% CI -0.003, -0.001, p = 0.03) was associated with decline in global cognition, independent of brain atrophy and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p=0.03). CONCLUSION(S): These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.

Using a case-control design, we determined risk factors associated with hypertension in a disadvantaged rural population in southern India. Three hundred adults with hypertension and 300 age- and sex-matched controls were extensively phenotyped. Underweight (29%, body mass index < 18.0 kg m-2), chronic kidney disease (25%, estimated glomerular filtration rate <60 ml min-1 1.73 m-2) and anemia (82%) were highly prevalent. The ratio of sodium to potassium excretion was high (8.2). In multivariable conditional logistic regression of continuous variables dichotomized by their median value, hypertension was independently associated with greater abdominal adiposity as assessed by waist-hip ratio [odds ratio (95% confidence interval), 1.89 (1.21-2.97)], lesser protein intake as assessed by 24 h urea excretion [0.39 (0.24-0.65)], and lesser plasma renin activity [0.54 (0.35-0.84)]. Hypertension tended to be independently associated with lesser serum potassium concentration [0.66 (0.44-1.01), P = 0.06]. Furthermore, those with hypertension reported less frequent intake of vegetables and urinary sodium-potassium ratio correlated positively with serum sodium-potassium ratio (r = 0.18). Hypertension was also independently associated with lesser blood hemoglobin concentration [0.48 (0.26-0.88)]. Blood hemoglobin concentration was positively associated with serum iron (r = 0.41) and ferritin (r = 0.25) concentration and negatively associated with total iron binding capacity (r = -0.17), reflecting iron-deficiency anemia. Our findings indicate potential roles for deficient intake of potassium and protein, and iron-deficiency anemia, in the pathophysiology of hypertension in a setting of disadvantage in rural India. Imbalanced intake of potassium and sodium may be driven partly by deficient intake of vegetables or fruit.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.

Objectives: Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. Method(s): In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume, and subcortical volume. Result(s): Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P=.024) for TBV, where the inverse association age with TBV was steeper in women (beta=-5.35 mL/year) than in men (beta=-4.77 mL/year). Similar age-sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P=.007) where the inverse association of age with TBV was steeper in postmenopausal (beta=-5.89 mL/year) than in pre/perimenopausal women (beta=-1.61 mL/year). Similar age-menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age-sex and age-menopause interactions were found for regional cortical and subcortical brain volumes. Conclusion(s): Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.Copyright © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Introduction: Greater double support time (DST) variability is associated with falls and memory decline. The underlying neurophysiological mechanisms of DST variability are poorly understood. Simple reaction time (SRT) variability, a measure of attention-processing speed is associated with falls and dementia and, may underlie greater DST variability. The aims of this study were to examine the association between SRT and DST variability and if SRT variability mediates the associations between poorer cognition/brain structure and DST variability. Method(s): Participants (n = 408) were community-dwelling older people without dementia (mean age 72.0 +/- 7.0). DST variability was the standard deviation (SD) of DST, assessed with a walkway and averaged across steps of 6 walks. SRT variability was the SD of a button pressing task in response to a visual stimulus. Executive function and processing speed were assessed with neuropsychological tests. Magnetic Resonance Imaging was used to obtain cortical thickness (total and in frontal regions) and cerebral small vessel disease (cSVD). Multivariable linear regression models were used to examine the association between SRT and DST variability and if SRT variability mediated any associations of cognition/brain structure with DST variability. Result(s): Greater SRT variability was associated with greater DST variability (p = 0.002). SRT variability partially mediated the association between poorer executive function and greater DST variability. Smaller mean thickness in orbitofrontal regions and greater cSVD burden were only associated with DST variability (p < 0.05), not with SRT variability (p > 0.05). Conclusion(s): Greater SRT variability, which may occur due to inefficient executive functioning, could be an underlying neurophysiological mechanism of greater DST variability.Copyright © 2021 Elsevier B.V.

Background--Various indicators of socioeconomic position (SEP) may have opposing effects on the risk of hypertension in disadvantaged settings. For example, high income may reflect sedentary employment, whereas greater education may promote healthy lifestyle choices. We assessed whether education modifies the association between income and hypertension in 3 regions of South India at different stages of epidemiological transition. Methods and Results--Using a cross-sectional design, we randomly selected villages within each of rural Trivandrum, West Godavari, and Rishi Valley. Sampling was stratified by age group and sex. We measured blood pressure and anthropometry and administered a questionnaire to identify lifestyle factors and SEP, including education, literacy, and income. Logistic regression was used to assess associations between various components of SEP and hypertension, and interaction analyses were used to determine whether educational attainment modified the association between income and hypertension. Trivandrum, the region of highest SEP, had the greatest prevalence of hypertension, whereas Rishi Valley, the lowest SEP region, had the least. Overall, greater income was associated with greater risk of hypertension. In interaction analyses, there was no evidence that educational attainment modified the association between income and hypertension. Conclusions--Education is widely considered to ameliorate the risk of hypertension in high-income countries. Why this effect is absent in rural India merits investigation. ( J Am Heart Assoc. 2020;9:e014486. DOI: 10.1161/JAHA.119.014486.).Copyright © 2020 The Authors.

Background: We have shown a decline in the annual rate of TIA in Victoria over 10 years. In this study, we evaluate if there are local hotspots or regional trends over time in the TIA rate. Method(s): Victorian hospital admitted episode (VAED) data was used to collect TIA cases from 2001- 2011 within Local Government Areas (LGA) in Victoria defined with ICD-10-AM codes. Standardised TIA ratios (STR) for each LGA per year was calculated by dividing actual over expected cases. The geocodes of the boundaries of each LGA was retrieved from the Australian Bureau of Statistics. Choropleth (thematic) maps were created to depict STR over time. We used Bayesian methods with Integrated Nested Laplace Approximation (INLA), adjusting for hypertension, sex and population count within the area. A Poisson regression model was built as the baseline model. Using a stepwise manner, a spatial random effect was added into the baseline model, followed finally by a temporal component. Models were compared using Deviance Information Criterion (DIC) andWatanabe-Akaike information criteria (WAIC). Result(s): Choropleth maps showed a higher STR in North-West Victoria. Compared to the baseline model (DIC 14,236, WAIC 14,267), adding in a spatial random effect significantly improved the model (DIC 6,472, WAIC 6,674). However, adding a temporal component did not lead to a significant improvement. (DIC 6,492, WAIC 6,714). Conclusion(s): There is a strong spatial component to the TIA rate over regional Victoria but no temporal change over 10 years at a regional level.

Objective: To determine whether there is an interaction between knowledge about hypertension and awareness of hypertension on the treatment and control of hypertension in three regions of South India at different stages of epidemiological transition (see Video, Supplemental Digital Content 1, http://links.lww.com/HJH/B426). Method(s): Using a cross-sectional design, we randomly selected villages within each of rural Trivandrum, West Godavari, and Chittoor. Sampling was stratified by age group and sex. We measured blood pressure and administered a questionnaire to determine knowledge and awareness of hypertension. Logistic regression was used to assess associations of awareness and knowledge about hypertension with its treatment and control in participants with hypertension, while examining for statistical interaction. Result(s): Among a total of 11 657 participants (50% male; median age 45 years), 3455 had hypertension. In analyses adjusted for age and sex, both knowledge score [adjusted odds ratio (aOR) 1.14 [95% confidence interval (CI) 1.12- 1.17)] and awareness [aOR 104 (95% CI 82-134)] were associated with treatment for hypertension. Similarly, both knowledge score [aOR 1.10; 95% CI (1.08-1.12)] and awareness [aOR 13.4; 95% CI (10.7-16.7)], were positively associated with control of blood pressure in those with hypertension, independent of age and sex. There was an interaction between knowledge and awareness on both treatment and control of hypertension (P of attributable proportion <0.001 for each). Conclusion(s): Health education to improve knowledge about hypertension and screening programs to improve awareness of hypertension may act in an additive fashion to improve management of hypertension in rural Indian populations.Copyright © 2021 Lippincott Williams and Wilkins. All rights reserved.

Background: To improve the control of hypertension in low- and middle-income countries, we trialed a community-based group program co-designed with local policy makers to fit within the framework of India's health system. Trained accredited social health activists (ASHAs), delivered the program, in three economically and developmentally diverse settings in rural India. We evaluated the program's implementation and scalability. Method(s): Our mixed methods process evaluation was guided by the United Kingdom Medical Research Council guidelines for complex interventions. Meeting attendance reports, as well as blood pressure and weight measures of attendees and adherence to meeting content and use of meeting tools were used to evaluate the implementation process. Thematic analysis of separate focus group discussions with participants and ASHAs as well as meeting reports and participant evaluation were used to investigate the mechanisms of impact. Result(s): Fifteen ASHAs led 32 community-based groups in three rural settings in the states of Kerala and Andhra Pradesh, Southern India. Overall, the fidelity of intervention delivery was high. Six meetings were delivered over a 3-month period to each of the intervention groups. The mean number of meetings attended by participants at each site varied significantly, with participants in Rishi Valley attending fewer meetings [mean (SD) = 2.83 (1.68)] than participants in West Godavari (Tukeys test, p = 0.009) and Trivandrum (Tukeys test, p < 0.001) and participants in West Godavari [mean (SD) = 3.48 (1.72)] attending significantly fewer meetings than participants in Trivandrum [mean (SD) = 4.29 (1.76), Tukeys test, p < 0.001]. Culturally appropriate intervention resources and the training of ASHAs, and supportive supervision of them during the program were critical enablers to program implementation. Although highly motivated during the implementation of the program ASHA reported historical issues with timely remuneration and l

We assessed the association of hypertension with markers of inflammation and infection in a rural and disadvantaged Indian population. In a case-control study, we age- and gender-matched 300 cases with hypertension to 300 controls without hypertension. Blood pressure was measured according to a strict protocol. We measured markers of inflammation and infection including serum high-sensitivity C-reactive protein (hs-CRP), blood lymphocyte count, serum homocysteine, tooth loss, overcrowding and exposure to fecal contamination. Multivariable conditional logistic regression was used to determine their association with hypertension. Median serum hs-CRP was 42% greater in cases than controls, while median serum homocysteine was 10% greater. In multivariable conditional logistic regression, elevated homocysteine (OR 1.75, 95% CI 1.09-2.82), greater lymphocyte count (OR 1.49, 95% CI 1.01-2.01) and exposure to fecal contamination, defined as a distance from the field used for toilet purposes to the household of <=50 m (OR 2.38, 95% CI 1.07-5.29), were independently associated with hypertension in this rural population. In separate analyses for each gender, elevated hs-CRP (OR 2.62, 95% CI 1.04-6.58) was associated with hypertension in men, whereas edentulism (OR 4.75, 95% CI 1.62-13.96) was associated with greater odds of hypertension in women. Our findings demonstrate specific associations between hypertension and markers of inflammation and infection including hs-CRP, homocysteine, lymphocyte count, edentulism and exposure to fecal contamination. Thus, strategies aimed at reducing inflammation and infection may reduce the burden of hypertension in such settings of disadvantage in rural India.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Background and objectives Older adults with cognitive impairment are vulnerable to frequent hospital admissions and emergency department presentations. The aim of this study was to use a codesign approach to develop MyCare Ageing, a programme that will train volunteers to provide psychosocial support to older people with dementia and/or delirium in hospital and at home when discharged from hospital. Setting Melbourne, Victoria, Australia. Research design This study adopts an action research methodology. We report on two co-design workshops with keystakeholders: Workshop 1: identification of components from three existing programmes to inform the development of the MyCare Ageing program logic and, Workshop 2: identification of implementation strategies. Participants The key stakeholders and workshop participants included clinicians (geriatricians, nurses and allied health), hospital staff (volunteer coordinators and hospital executives), Baptcare staff, a consumer, researchers and implementation experts and project staff. Results Workshop 1 identified the components from three existing programmes - the Volunteer Dementia and Delirium Care programme, Home-Start and MyCare for inclusion in MyCare Ageing. In workshop 2, the p implementation plan was developed taking into consideration hospital-specific processes, training and support needs of volunteers and safety and risk management processes. Discussion and conclusion The codesign process was successfully applied to develop the MyCare Ageing programme to provide volunteer support to patients with dementia and/or delirium in hospital and their transition home. MyCare Ageing is an innovative programme that meets an identified need from hospitals and consumers to support patients with dementia and/or delirium to improve psychosocial outcomes on discharge from hospital.Copyright © 2020 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke and adjusted the duration of arterial occlusion. At 1 day following stroke onset, the proportion of mice with infection was significantly greater in mice that had larger infarct sizes. Additionally, the presence of lung infection in these mice with severe strokes extended past 2 days, suggestive of long-term immune impairment. At the acute phase, our data demonstrated an inverse relationship between infarct volume and the number of circulating leukocytes, indicating the elevated risk of infection in more severe stroke is associated with reduced cellularity in peripheral blood, owing predominately to markedly decreased lymphocyte numbers. In addition, the stroke-induced reduction of lymphocyte-to-neutrophil ratio was also evident in the lung of all post-stroke animals. To investigate the effect of infarct location on post-stroke infection, we additionally performed a photothrombotic (PT) model of stroke and using an innovative systematic approach of analysis, we found the location of cerebral infarct does not impact on the susceptibility of post-stroke infection, confirming the greater role of infarct volume over infarct location in the susceptibility to infection. Our experimental findings were validated in a clinical setting and reinforced that stroke severity, and not infarct location, influences the risk of infection after stroke.Copyright © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Background New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). Methods and findings We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP >= 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diast

OBJECTIVES: Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. METHOD(S): In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume. RESULT(S): Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (beta = -5.35 mL/year) than in men (beta = -4.77 mL/year). Similar age-sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (beta = -5.89 mL/year) than in pre/perimenopausal women (beta = -1.61 mL/year). Similar age-menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age-sex and age-menopause interactions were found for regional cortical and subcortical brain volumes. CONCLUSION(S): Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

OBJECTIVE: To determine whether there is an interaction between knowledge about hypertension and awareness of hypertension on the treatment and control of hypertension in three regions of South India at different stages of epidemiological transition (see Video, Supplemental Digital Content 1, http://links.lww.com/HJH/B426). METHOD(S): Using a cross-sectional design, we randomly selected villages within each of rural Trivandrum, West Godavari, and Chittoor. Sampling was stratified by age group and sex. We measured blood pressure and administered a questionnaire to determine knowledge and awareness of hypertension. Logistic regression was used to assess associations of awareness and knowledge about hypertension with its treatment and control in participants with hypertension, while examining for statistical interaction. RESULT(S): Among a total of 11 657 participants (50% male; median age 45 years), 3455 had hypertension. In analyses adjusted for age and sex, both knowledge score [adjusted odds ratio (aOR) 1.14 [95% confidence interval (CI) 1.12--1.17)] and awareness [aOR 104 (95% CI 82--134)] were associated with treatment for hypertension. Similarly, both knowledge score [aOR 1.10; 95% CI (1.08--1.12)] and awareness [aOR 13.4; 95% CI (10.7--16.7)], were positively associated with control of blood pressure in those with hypertension, independent of age and sex. There was an interaction between knowledge and awareness on both treatment and control of hypertension (P of attributable proportion <0.001 for each). CONCLUSION(S): Health education to improve knowledge about hypertension and screening programs to improve awareness of hypertension may act in an additive fashion to improve management of hypertension in rural Indian populations.

Background The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people. Methods People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume. Results At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty. Conclusions We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty.

Background: Hospital, emergency presentation and death databases are frequently used to research outcomes after stroke. The reliability of diagnostic coding for cardiovascular disease (CVD) in these administrative data remains uncertain. We aimed to determine the reliability of these data in Australia using an existing clinical trial cohort. Method(s): Patients with stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563, recruited from 4 hospitals within Victoria). We used diagnostic ICD-10-AM coded data from hospital, emergency department and death databases within 2 years after stroke/TIA. Medical records for these potential CVD-related events were reviewed by two independent stroke specialists and adjudicated according to strict criteria. We then estimated sensitivity and specificity of using either primary or both primary and secondary diagnoses fields (obtained for all adjudicated records), against the events adjudicated by the specialists (gold standard). False positives were CVD-events defined by ICD-10-AM diagnostic codes that were adjudicated as not being a CVD-event. False negatives were true CVD-events that were misclassified as not being CVD-related when using ICD-10-AM codes. Result(s): We identified 261 events for medical review. After adjudication, 65 were classified as CVD-events (cases) and 196 were not CVD-events. Using both primary and secondary diagnoses, 55 true positives were correctly identified among the cases (sensitivity = 84.6%) and 129 true negatives among the non-cases (specificity = 65.8%). Using only primary diagnoses, 48 true positives were identified (sensitivity = 73.9%) and 171 true negatives (specificity = 87.2%). Using both primary and secondary diagnoses had an increased sensitivity, but decreased specificity (area under the Receiver Operating Characteristic curve (AUC) = 0.75; 95% CI, 0.70, 0.81) when compared with using only primary dia

Background: Greater age and female sex are risk factors for dementia. Menopause is associated with cognitive dysfunction and may contribute to dementia risk. Previous work has considered the effects of aging and menopause as additive. We aimed to study whether aging and menopause interact to amplify each other's effect on imaging biomarkers of dementia. Method(s): Cross-sectional study of participants with detailed structural brain magnetic resonance imaging data from the UK Biobank, a community-based cohort of men and women over 40 years of age in the United Kingdom. Using linear regression modeling we explored the associations of age, sex and menopausal status with total brain volume (TBV), examining for interactions, and adjusting for APOE4 status. Result(s): Data were available for 1824 postmenopausal women, 233 premenopausal women and 2165 men (median age 63.3, range 44.6-78.0 years). There was an interaction between sex and age (p<0.01) such that the negative association of age with TBV was greater in women (beta= -5.42, 95% CI: -5.75 to -5.10) than men (beta= -4.74, 95%CI: -5.54 to -3.94). In women, there was an interaction between menopausal status and age (p=0.01) such that the negative association of age with TBV was greater in post-menopausal women (beta= -5.89, 95% CI:-6.33 to -5.45) than pre-menopausal women (beta= -2.87, 95% CI:-5.70 to -0.04). Use of hormonal replacement therapy did not significantly alter this relationship. Conclusion(s): Increasing age, female sex, and the occurrence of menopause appears to have synergistic effects on TBV. Further work is required to understand the mechanisms driving these associations, to develop ways to prevent or delay neurodegeneration and dementia.Copyright © 2019

Background and purpose: Limited evidence exists on the benefits of organized care for improving risk factor control in patients with stroke or transient ischaemic attack. The effectiveness of an individualized management programme in reducing absolute cardiovascular disease risk in this high-risk population was determined. Method(s): This was a prospective, multicentre, cluster-randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients hospitalized for stroke/transient ischaemic attack and aged >=18 years were recruited from four hospitals. General practices treating recruited patients were randomized to provide either usual care or an individualized management programme comprising nurse-led education and review of care plans by stroke specialists in addition to usual care. The primary outcome was a change in cardiovascular Framingham Risk Score between baseline and 12 months. Result(s): From January 2010 to November 2013, 156 general practices (280 patients) were randomly assigned to usual care (control) and 159 (283 patients) to the intervention. The median age was 70.1 years; 65% were male. Overall, >80% of participants were prescribed recommended secondary prevention therapies at baseline. The primary efficacy analysis comprised 533 participants, with 30 either dying or lost to follow-up. In adjusted analyses, no significant between-group difference was found in the cardiovascular risk score at 12 months (0.04, 95% confidence interval -1.7, 1.8). Conclusion(s): The effectiveness of an organized secondary prevention programme for stroke may be limited in patients from high-performing hospitals with regular post-discharge follow-up and communication with general practices.Copyright © 2017 EAN

Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-alpha production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection.Copyright © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Background: Prognostic performances of models predicting risk of recurrent events of cardiovascular disease (CVD) are not adequate for use in clinical settings. We aimed to determine whether adapting the Framingham Risk Score (FRS) to an Australian population could effectively predict recurrent cardiovascular outcomes. Method(s): Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Cox proportional hazards regression models were used to determine the risk of recurrence of CVD-related events and deaths within 3 years after stroke/TIA; adjudicated by two independent stroke specialists. Regression estimates were then used to recalibrate the coefficients used by the FRS, and performance of the model assessed. Result(s): In women, the recalibrated FRS model had poor discrimination (C-statistic = 0.634) and appeared to better predict CVD recurrence (AUC = 0.664) than the original FRS model (AUC = 0.598). However in men, the recalibrated FRS model had poor discrimination (C-statistic = 0.604) and prediction of CVD recurrence (AUC = 0.632) similar to the original FRS model (AUC = 0.606). Conclusion(s): The original FRS and recalibrated FRS models appeared to perform poorly in Australian men and women with stroke. The identification of relevant risk factors, easily measured in a clinical setting, may help clinicians better monitor the risks of their patients and enhance secondary prevention strategies.

Background: Chronic Disease Management (CDM) plans are usually administered by general practitioners (GPs) to assist those with a chronic medical condition, such as stroke, and provide better management of risk factors. Despite the prevalent use of CDM plans, its comprehensiveness and the fact that there is a government commitment to fund it, there is limited evidence of its effectiveness in Australian survivors of stroke. We aimed to assess the effectiveness of CDM plans on preventing the recurrence of CVD-related serious adverse events. Method(s): Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n = 563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Poisson regression models were used to determine the incidence rate ratio (IRRs) of increasing exposure to being on a CDM plan over 3 years, while adjusting for confounding factors. We used the total count of CVD-related events and deaths within 3 years after stroke/TIA, based on either hospital discharge codes or adjudication by two independent stroke specialists. Result(s): Five hundred and sixty-three patients were included (median age 70; 36% female). There were 305 CVD-related events over the three years (mean 0.54), in which a third (104) were adjudicated and two-thirds (201) were derived from hospital discharge codes alone. Nearly a quarter (27%) did not take up a CDM plan over the three years, a third (33%) were on plans for less than 1.5 years and 40% were on plans from 1.5 years to 3 years. The factors most strongly associated with decreased incidence of CVD-related events were duration on a CDM plan (Adjusted IRR (aIRR) 0.85, 95% confidence interval (95%CI) 0.77-0.93; p<0.001), higher level of education (aIRR 0.55, 95%CI 0.42-0.71; p<0.001), more physically active occupation (aIRR 0.54, 95%CI 0.41

Background: Prognostic performances of models predicting risk of recurrent events of cardiovascular disease (CVD) are not adequate for use in clinical settings. We aimed to determine whether adapting the Framingham Risk Score (FRS) to an Australian population could effectively predict recurrent cardiovascular outcomes. Method(s): Patients comprised survivors of stroke/TIA who participated in the Shared Team Approach between Nurses and Doctors For Improved Risk factor Management (STAND FIRM) trial (n=563). We used standardised anthropometric, biochemical and blood pressure data, collected at baseline, to evaluate risk factors for stroke/TIA. Cox proportional hazards regression models were used to determine the risk of recurrence of CVD-related events and deaths within 2 years after stroke/ TIA; adjudicated by two independent stroke specialists. Regression estimates were then used to recalibrate the coefficients used by the FRS, and performance of the model assessed. Result(s): In men, the recalibrated FRS model had poor discrimination (C-statistic=0.607) and appeared to better predict CVD recurrence (AUC=0.608) than the original FRS model (AUC=0.515). However in women, the recalibrated FRS model had poor discrimination (Cstatistic =0.626) and prediction of CVD recurrence (AUC=0.571) similar to the original FRS model (AUC=0.617). Conclusion(s): The original FRS and recalibrated FRS models appeared to perform poorly in Australian men and women with stroke. The identification of relevant risk factors, easily measured in a clinical setting, may help clinicians better monitor the risks of their patients and enhance secondary prevention strategies.

Background and Purpose - Human amnion epithelial cells (hAECs) are nonimmunogenic, nontumorigenic, antiinflammatory cells normally discarded with placental tissue. We reasoned that their profile of biological features, wide availability, and the lack of ethical barriers to their use could make these cells useful as a therapy in ischemic stroke. Methods - We tested the efficacy of acute (1.5 hours) or delayed (1-3 days) poststroke intravenous injection of hAECs in 4 established animal models of cerebral ischemia. Animals included young (7-14 weeks) and aged mice (20-22 months) of both sexes, as well as adult marmosets of either sex. Results - We found that hAECs administered 1.5 hours after stroke in mice migrated to the ischemic brain via a CXC chemokine receptor type 4-dependent mechanism and reduced brain inflammation, infarct development, and functional deficits. Furthermore, if hAECs administration was delayed until 1 or 3 days poststroke, long-term functional recovery was still augmented in young and aged mice of both sexes. We also showed proof-of-principle evidence in marmosets that acute intravenous injection of hAECs prevented infarct development from day 1 to day 10 after stroke. Conclusions - Systemic poststroke administration of hAECs elicits marked neuroprotection and facilitates mechanisms of repair and recovery.Copyright © 2018 American Heart Association, Inc.

Blood pressure (BP) is variable in children and this could affect BP assessment, but the magnitude of within-visit BP variability (BPV) over consecutive measurements has never been investigated. This study aimed to determine the direction and magnitude of, and factors affecting, within-visit BPV in children and adolescents. BP was recorded among 3047 children (aged 12 years [95%CI 12, 13], males 52%) from the 2011-2013 Australian Health Survey. BPV was defined as the absolute difference (SBPABS) between the first (SBP1) and second systolic BP (SBP2) and the overall variability in three measures when available (SBPV). On average, SBPABS was 6.7 mmHg (95%CI 6.3, 7.0) and SBPV was 8.2% (95%CI 7.8, 8.6). SBPABS was greater with higher BP levels but lower with older age. From first to second measurements, SBP decreased in 58% (95%CI 56, 60), did not change in 10% (95%CI 9, 12), and increased in 32% (95%CI 29, 34) of the population. Conclusion(s): BP is highly variable in children and adolescents, with the magnitude of variability being associated with both age and BP level. SBP increases on repeat measurement in a substantial proportion of the population. The optimal protocol of BP assessment to address this increased BPV needs to be determined.What is Known:* Diagnosis of elevated blood pressure (BP) is based on strict probabilistic criteria, the difference between the 90th (pre-hypertension) and 95th (hypertension) percentiles only being 3-4 mmHg.* BP variability could affect BP classification among children and adolescents.What is New:* The magnitude of BP change among children and adolescents is highly affected by BP level and age.* BP does not always drop on consecutive measurements, and evidence-based BP assessment protocols should be established to avoid misdiagnosis of hypertension.Copyright © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Severity of stroke impacts functional outcomes after stroke, but the role of this disability on secondary prevention is unclear. We investigated the effect of disability status on secondary prevention outcomes, such as the management of risk factors, knowledge regarding secondary prevention, and long-term unmet needs. Method(s): Post-hoc analysis of a clinical trial of community-dwelling adults with stroke/TIA in Melbourne, Australia. Demographic/clinical data were obtained from hospital records, while standardised assessments were conducted for disability, cardiovascular risk, and mood. Disability was defined using the modified Rankin Scale (mRS): no disability (mRS=0), no significant disability (mRS=1), or slight to severe disability (mRS 2-5). Two-year outcomes included the standardized cardiovascular Framingham risk score, unmet needs, and knowledge of risk factors and medications prescribed for secondary prevention. Multivariable regression models were used to determine the effect of disability status on outcomes. Result(s): From January 2010 to November 2013, 563 survivors of stroke/TIA were recruited: median age 70.1 years, 65% males, 79% ischemic stroke, and 29% with no disability. After a 2-year follow-up, 86% provided outcome data. In the multivariable regression analyses, when compared to participants with no significant disability, those with slight/severe disability had greater cardiovascular risk scores (odds ratio 1.33, 95% CI 1.00-1.76). A dose-response effect was found for disability status and long-term unmet needs, with more unmet needs reported among those with no significant disability (incidence risk ratio 1.55, 95% CI 1.21-1.99) or with slight/severe disability (incidence risk ratio 1.64, 95% CI 1.24-2.16), than in those with no disability. We found no effect of disability status on knowledge of risk factors or medications. Conclusion(s): After a 24-month follow-up, survivors of stroke/TIA with disability had worse risk profiles

Objectives: Based on anecdotal belief that blood pressure (BP) drops over consecutive measurements, guidelines recommend discarding the first BP reading (Canadian Hypertension Education Program guidelines) or take only one reading if SBP less than 140 mmHg (National Institute for Health and Care Excellence). However, the extent to which SBP fluctuations affect BP classification as well as the potential effect of age are unknown. We sought to assess the change in SBP classification over consecutive measurements following different guidelines, among younger (<50 years) and older individuals (>50 years). Furthermore, we aimed to investigate the direction of the change in SBP over consecutive measurements (increase or decrease) and the impact of age on SBP differences. Method(s): BP was measured among 20 716 adults from a general population. SBP was classified using the first reading (normal SBP or hypertension) and compared with the average SBP using different guideline protocols (reclassification). Result(s): Reclassification from normal SBP to hypertension was greatest with Canadian Hypertension Education Program guidelines (3% younger, 12% older individuals) and reclassification from hypertension to normal SBP was greatest with National Institute for Health and Care Excellence guidelines (70% younger, 44% older individuals). SBP increased between the first two measures in 37%, decreased in 56% and did not change in 7% of the population. Age had a strong interaction with SBP level (P< 0.0001) so that younger individuals exhibited greater SBP differences over repeated measures. Conclusion(s): This study highlights the need for an improvement in the evidence-base regarding the best way to assess office BP for correct hypertension diagnosis.Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

INTRODUCTION: Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment of hypertension may differ regionally according to economic development. Our main objectives are to estimate the prevalence, awareness, treatment and control of hypertension in 3 diverse regions of rural India; identify barriers to diagnosis and treatment in each setting and evaluate the feasibility of a community-based intervention to improve control of hypertension. METHODS AND ANALYSIS: This study includes 4 main activities: (1) assessment of risk factors, quality of life, socioeconomic position and barriers to changes in lifestyle behaviours in ~14 500 participants; (2) focus group discussions with individuals with hypertension and indepth interviews with healthcare providers, to identify barriers to control of hypertension; (3) use of a medicines-availability survey to determine the availability, affordability and accessibility of medicines and (4) trial of an intervention provided by Accredited Social Health Activists (ASHAs), comprising group-based education and support for individuals with hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion in the cross-sectional survey, with further randomisation to intervention or control. Changes in knowledge of hypertension and risk factors, and clinical and anthropometric measures, are assessed. Evaluation of the intervention by participants provides insight into perceptions of education and support of self-management delivered by the ASHAs. ETHICS AND DISSEMINATION: Approval for the overall study was obtained from the Health Ministry's Screening Committee, Ministry of Health and Family Welfare (India), institutional review boards at each site and Monash University. In addition to publication in peer-reviewed articles, results will be shared with federal, state and local government healt

The aim of this study was to identify factors associated with awareness, treatment and control of hypertension in a rural setting in India. Following screening of the population, all individuals with hypertension (blood pressure (BP) >=140/90 mm Hg or taking antihypertensive medications) were invited to participate in this study. We measured BP, height, weight, skinfolds, waist and hip circumference, and administered a questionnaire to obtain information regarding socioeconomic and behavioural characteristics. Multivariable logistic regression was used to determine factors associated with awareness, treatment and control of hypertension. We recruited 277 individuals with hypertension. Awareness (43%), treatment (33%) and control (27%) of hypertension were poor. Greater distance to health services (odds ratio (OR) 0.56 (95% confidence interval (CI)) 0.32-0.98) was associated with poor awareness of hypertension while having had BP measured within the previous year (OR 4.72, 95% CI 2.71-8.22), older age and greater per cent body fat were associated with better awareness. Factors associated with treatment of hypertension were having had BP measured within the previous year (OR 6.18, 95% CI 3.23-11.82), age >=65 years, physical inactivity and greater per cent body fat. The only factor associated with control of hypertension was greater per cent body fat (OR 1.05, 95% CI 1.01-1.11). Improving geographic access and utilisation of health services should improve awareness and treatment of hypertension in this rural population. Further research is necessary to determine drivers of control.Copyright © 2017 The Author(s).

Objective: To determine the risk of incident major cardiovascular atherothrombotic events in patients with chronic granulomatous disease (CGD); a rare genetically-determined immunodeficiency disorder caused by a defective NOX complex. Design(s): A population-level cohort study comparing the risk of incident coronary and cerebrovascular ischemic events between individuals with and without CGD. The sample was derived from hospitalizations within the Australian state of Victoria from 1993-2010. For each CGD admission, we selected all individuals from the non-CGD hospitalizations group matched for age to serve as the comparison group. Main Outcome Measure(s): Multivariable logistic regression was used to determine the risk of incident atherothrombotic events in CGD, adjusting for age, sex and vascular risk factors. Result(s): We identified 77 people with CGD (mean age at first admission, 44.ly) and 409, 512 people without (37. ly). A total of 15 (20.8%) CGD individuals and 26,134 (6.3%) non-CGD individuals suffered an atherothrombotic event during the study period. After adjusting for age and sex, CGD was associated with an increased risk of an incident atherothrombotic event, odds ratio [(OR) 2.64; 95% confidence interval (CI) 1.37-5.11; P=0.004]. This was due to an increase in risk of coronary events (OR, 2.39; 95% CI, 1.19-4.78; P=0.014) and cerebrovascular events (OR, 2.91; 95% CI, 1.11-7.62; P=0.029). CGD was also associated with a greater risk of hypertension, diabetes and atrial fibrillation, and further adjustment for the presence of these comorbidities attenuated the association of CGD with all atherothrombotic, coronary and cerebrovascular events. Conclusion and relevance: CGD is associated with an increased risk of incident atherothrombotic events, perhaps due to chronic inflammation. Thus, despite promising preclinical evidence, these observations suggest that chronic NOX suppression may not be a valid approach for the prevention of cardiovascular disease in

Introduction: Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). Method(s): Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged >=18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of >=5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. Result(s): Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score >= 5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged >=65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or >=4 medications (OR 0.09, 95% CI 0.02, 0

The aims of this study were to (1) determine if older people at their fast walking speed (FWS) are able to reach the speed required at pedestrian crossings (>1.2 m/s) and (2) determine the role of cognitive impairment on the ability to alter speed and walk quickly. Participants were recruited from the Angers Memory Clinic, France. Gait speed was assessed at preferred and FWS using a GAITRite walkway. Walking speed reserve (WSR) was calculated as the difference between FWS and preferred speeds. Participants were classified into cognitive stages (cognitively healthy, mild cognitive impairment, mild and moderate dementia) based on neuropsychological evaluations. The proportion of participants with a FWS of <1.2 m/s was reported. The association between cognitive stage and preferred, fast and walking speed reserve was assessed using multivariable regression, adjusting for covariates. The mean age of the sample (n = 681) was 73.3 (SD 5.8) years. At preferred speed 73.7%, and at FWS 12.8%, of participants had speeds less than 1.2 m/s. Poorer cognitive stage was associated with slower preferred speed (beta -0.08, 95% CI -0.10, -0.06), FWS (beta -0.13, 95% CI -0.16, -0.10) and also with smaller WSR (m/s) (beta -0.05, 95% CI -0.07, -0.03), but not WSR (%) (beta -1.73, 95% CI -4.38, 0.93). In older people, worse stages of cognitive impairment were associated with poorer ability to increase speed and walk quickly. Such limitations may result in reduced ability to access the community.Copyright © 2017, American Aging Association.

Background and Purpose - Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. Methods - Randomized controlled trial of survivors of stroke/transient ischemic attack aged >=18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. Results - Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was >=80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. Conclusions - The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change.Copyright © 2017 American Heart Association, Inc.

Background and Purpose-Despite the benefit of risk awareness in secondary prevention, survivors of stroke are often unaware of their risk factors. We determined whether a nurse-led intervention improved knowledge of risk factors in people with stroke or transient ischemic attack. Methods-Prospective study nested within a randomized controlled trial of risk factor management in survivors of stroke or transient ischemic attack. Intervention(s): 3 nurse education visits and specialist review of care plans. Outcome(s): unprompted knowledge of risk factors of stroke or transient ischemic attack at 24 months. Effect of intervention on knowledge and factors associated with knowledge were determined using multivariable regression models. Results-Knowledge was assessed in 268 consecutive participants from the main trial, 128 in usual care and 140 in the intervention. Overall, 34% of participants were unable to name any risk factor. In adjusted analyses, the intervention group had better overall knowledge than controls (incidence risk ratio, 1.26; 95% confidence interval, 1.00-1.58). Greater functional ability and polypharmacy were associated with better knowledge and older age and having more comorbidities associated with poorer knowledge. Conclusions-Overall knowledge of risk factors of stroke or transient ischemic attack was better in the intervention group than controls. However, knowledge was generally poor. New and more effective strategies are required, especially in subgroups identified as having poor knowledge. Clinical Trial Registration-URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000166370.Copyright © 2017 American Heart Association, Inc.

Background: The Motoric Cognitive Risk Syndrome (MCR) is characterized by slow gait speed and cognitive complaints. Objective(s): The objective of this study was to determine if the presence of MCR increases the risk of falls in older people. Method(s): Individual participant data (n=6,204) from five longitudinal studies from three countries were used for this analysis. MCR diagnosis was defined as both the presence of objectively measured slow gait speed and subjective cognitive complaints in those without dementia or mobility disability. Falls were prospectively ascertained using phone calls or questionnaires. Log binomial regression was performed to determine if MCR increased the risk of falls separately in each cohort. Random effects meta-analysis was used to pool results from all cohorts. Result(s): The mean age of participants was 74.9 (SD 6.8) years and 44 (n=2728) were male. Overall 33.9 (n=2104) reported a fall over follow-up. Pooled relative risk of MCR with any falls was RR 1.44 95 CI 1.16, 1.79. The components of MCR, slow gait (RR 1.30 95 CI 1.14, 1.47) and cognitive complaint (RR 1.25, 95 CI 1.07, 1.46) were also associated with an increased risk of any falls. In sub-analyses MCR was associated with any fall independent of previous falls (RR 1.29 95 CI 1.09, 1.53) and with multiple falls (RR 1.77, 95 CI 1.25, 2.51). Conclusion(s): MCR is associated with an increased risk of falls. The increase in risk was higher than for its individual components. The simplicity of the MCR makes it an attractive falls risk screening tool for the clinic.Copyright © 2016 - IOS Press and the authors. All rights reserved.

Aims: In a population-based study of older people to examine whether 1) overall gait initiation (GI) time or its components are associated with falls and 2) GI under dual-task is a stronger predictor of falls risk than under single-task. Method(s): Participants aged 60-85 years were randomly selected from the electoral roll. GI was obtained with a force platform under both single and dual-task conditions. Falls were ascertained prospectively over a 12-month period. Log multinomial regression was used to examine the association between GI time (total and its components) and risk of single and multiple falls. Age, sex and physiological and cognitive falls risk factors were considered as confounders. Result(s): The mean age of the sample (n = 124) was 71.0 (SD 6.8) years and 58.9% (n = 73) were male. Over 12 months 21.8% (n = 27) of participants reported a single fall and 16.1% (n = 20) reported multiple falls. Slower overall GI time under both single (RR all per 100 ms 1.28, 95%CI 1.03, 1.58) and dual-task (RR 1.14, 95%CI 1.02, 1.27) was associated with increased risk of multiple, but not single falls (p < 0.05). Multiple falls were also associated with slower time to first lateral movement under single-task (RR 1.90 95%CI 0.59, 1.51) and swing time under dual-task condition (RR 1.44 95%CI 1.08, 1.94). Conclusion(s): Slower GI time is associated with the risk of multiple falls independent of other risk factors, suggesting it could be used as part of a comprehensive falls assessment. Time to the first lateral movement under single-task may be the best measures of this risk.Copyright © 2016 Elsevier B.V.

Background and Aim: The use of evidence-based care plans in general practice improves the control of diabetes and blood pressure, but its efficacy in stroke is unknown. We aimed to determine whether an organized program of care reduced the absolute risk of cardiovascular disease in patients with stroke or TIA when compared to usual care. Method(s): In this prospective, multicenter, randomized controlled trial, we included patients hospitalized with stroke/TIA, and excluded those living >50 km from a recruitment center, recruited to another clinical trial, or discharged to a nursing home. The intervention, clustered by general practice, comprised 1) a care plan, individualized to patient's risk factors and reviewed by a specialist, that was used to communicate optimal management between patients and their General Practitioner; and 2) homebased nurse-led education and support about risk factor management. Outcome assessors were blinded to treatment group. A sample size of 570, allowing for 20% dropouts, was required to detect a 4.5% difference in 10-year Framingham Cardiovascular Risk Score between groups; this being the primary outcome. Result(s): A total of 570 patients were recruited from four hospitals; mean age 69 years (SD 14), 65% male, 77% ischemic stroke, 19% intracerebral hemorrhage and 14% TIA. The primary outcome had <10% missing data. Conclusion(s): With only half the dropouts expected, STANDFIRM has sufficient power for its primary outcome measure. If effective this readily applicable program, which can be funded through Medicare Benefits, will enable General Practitioners to more effectively manage their patients with stroke or TIA.

Measurement reliability of the L4/5 lumbar multifidus (MF) muscles is high in older adults, but few studies have investigated measurement reliability of the abdominal and upper lumbar MF muscles in this age group. Objectives To determine measurement reliability of abdominal and lumbar MF muscles from a single ultrasound (US) image in older adults. Methods Resting thickness of rectus abdominis and obliquus externus, resting and contracted thickness of obliquus internus, transversus abdominis and lumbar MF, and resting cross-sectional area (CSA) of MF levels (L2-5) were obtained from US images of 92 community-dwelling older adults (aged 65-89 years). Measurements of images were undertaken by an experienced rater and repeated 7-10 days later for intra-rater, and by a second expert rater for inter-rater calculations. Intra-rater reliability was estimated for all muscles. Inter-rater reliability was estimated for all abdominal muscles and for L5 multifidus. Reliability was estimated by intraclass correlation coefficients (ICC). Results Intra-rater ICC(3,1) and inter-rater ICC(2,1) of resting thickness measures of all muscles and CSA of MF were >=0.86. The ICCs for percentage thickness change were >=0.76 for the abdominal muscles, and >=0.42 for MF. Conclusions Measurement reliability of US imaging for abdominal and MF muscle thickness and MF CSA was high, and consistent with previous findings for younger adults. Reliability of percentage thickness change was lower suggesting caution is needed when using this as an outcome measure or study factor among older adults.Copyright © 2016 Elsevier Ltd

Background: Diagnostic coding is frequently used in stroke research. However, few data exist regarding the accuracy of Transient Ischemic Attack (TIA) codes in Australia. Aim(s): To determine the accuracy of ICD-10 Australian Modification (AM) diagnostic codes assigned to patients with neurologist diagnosed TIA. Method(s): ICD-10AM codes were identified for patients with suspected TIA treated at Monash Medical Centre, Australia (2004-2007). Coding accuracy was assessed against final neurologist diagnosis using the 24-hour criterion (clinical TIA). Assignment of a TIA code of G45.3, G45.8 or G45.9 to a patient with neurologist confirmed TIA was considered true positive and TIA mimics were considered false positives. Result(s): ICD-10AM codes were available for 336/488 (68.9%; 95% Confidence Interval 64.6%-72.8%) patients. Clinical TIA was confirmed in 209/336 (62.2%; 56.9%-67.2%). Evaluation of ICD-10AM codes for clinical TIA revealed: sensitivity 0.76 (0.69-0.81), specificity 0.43 (0.34-0.51), Positive Predictive Value 0.68 (0.62-0.74), Negative Predictive Value 0.51 (0.42-0.61). Mean age was slightly higher in those assigned a TIA code (66.4+/-13.7) compared with a non-TIA code (62.3+/-15.6; p < 0.02). Patients with symptoms lasting less than one hour were more likely to be assigned a TIA code than those with symptoms lasting more than one hour (p < 0.001). Discussion(s): ICD10AM codes are sensitive for clinical TIA, but insufficiently specific. These data may help to estimate measurement error when using administrative datasets for TIA research.

Blood pressure variability is associated with macrovascular complications and stroke, but its association with the microcirculation in type II diabetes has not been assessed. This study aimed to determine the relationship between blood pressure variability indices and retinal arteriolar diameter in non-diabetic and type II diabetes participants. Digitized retinal images were analysed to quantify arteriolar diameters in 35 non-diabetic (aged 52 +/- 11 years; 49% male) and 28 type II diabetes (aged 61 +/- 9 years; 50% male) participants. Blood pressure variability was derived from 24-h ambulatory blood pressure. Arteriolar diameter was positively associated with daytime rate of systolic blood pressure variation (p = 0.04) among type II diabetes participants and negatively among non-diabetics (p = 0.008; interaction p = 0.001). This finding was maintained after adjusting for age, sex, body mass index and mean daytime systolic blood pressure. These findings suggest that the blood pressure variability-related mechanisms underlying retinal vascular disease may differ between people with and without type II diabetes.Copyright © SAGE Publications.

Background: Although Type 2 diabetes (T2DM) is associated with retinal vascular disease, the underlying pathophysiological mechanisms are unclear. Reduced retinal arteriolar diameter has been linked to high clinic blood pressure (BP) but the role of more sensitive measures of BP control have never been assessed. This study aimed to determine the relationship between retinal arteriolar diameter and 24 hour ambulatory BP (including BP variability) in people with and without T2DM. Method(s): Digitized retinal photographs were analysed to quantify retinal arteriolar diameters in 37 non-diabetic (aged 53+/-10 years; 48.2% male) and 29 T2DM (aged 60+/-9 years; 48.6% male) participants. Daytime rate of systolic BP variation (BPV) was derived from 24 hour ambulatory BP as the 3-hour moving average for the slope of the change in systolic BP between each systolic BP reading over time. Result(s): There was a non-significant trend for patients with T2DM to have greater BPV compared with non-diabetics (35.9+/-7.1 versus 32.6+/-6.6; p = 0.08). BPV was significantly and negatively associated with retinal arteriolar diameter in non-diabetics alone (beta = -0.006, p = 0.03), but not in people with T2DM (beta = 0.004, p = 0.402), even after adjusting for age, body mass index and ambulatory systolic BP (either night time, day time or 24 hour systolic BP). Conclusion(s): BPV was inversely related to retinal arteriolar diameter only in people without T2DM. This suggests that mechanisms underlying retinal vascular disease may differ between people with and without T2DM, with the rate of BP variation possibly being an important factor.

Background: White matter hyperintensities increase the risk of multiple falls in older people, but the effect of sub-cortical infarcts is unknown. Aim(s): By pooling data from two Australian population-based studies, we aimed to investigate the association between sub-cortical infarcts and multiple falls and whether this relationship, and that of white matter hyperintensities, is mediated or modified by cognitive or sensorimotor factors. Method(s): Participants underwent structural magnetic resonance imaging and cognitive and sensorimotor assessments. Falls were prospectively measured over 12 months. Sub-cortical infarcts were detected visually. Total white matter hyperintensity volume was quantified using automated segmentation methods. Generalized linear models were used to examine if sub-cortical infarcts and white matter hyperintensities predicted falls. Result(s): The mean age of the sample (n=655) was 74.5 (standard deviation 6.7) years, 336 (51.3%) males. Overall, 114 (17.4%) had multiple falls. The majority had no sub-cortical infarcts (n=491, 75.0%), while 90 had one (13.7%), 41 had two (6.3%), and 33 had more than or equal to three sub-cortical infarcts (5.0%). The risk of multiple falls was elevated in people with more than or equal to three sub-cortical infarcts (adjusted relative risk 1.89, 95% confidence interval 1.03, 3.46) and in the highest quarter of white matter hyperintensity volume (adjusted relative risk 1.46, 95% confidence interval 1.00, 2.13). The effect of sub-cortical infarcts on falls was amplified by poorer vision (P=0.03). The effect of white matter hyperintensities was amplified by poorer vision (P=0.008), proprioception (P=0.03), and muscle strength (P=0.008). There was no modifying effect of cognitive function. Conclusion(s): Increasing burdens of sub-cortical infarcts and white matter hyperintensities are associated with a risk of falling. Interventions targeting sensorimotor factors along with strategies to prevent sub-cortical inf

Background Improved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS. Methods and Findings A population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993-2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4

We previously demonstrated the safety and effectiveness of a nonadmission-based model for TIA care (Monash TIA Triaging Treatment [M3T]). In this microcosting study, we used a pre-post cohort design with multivariable uncertainty analyses to compare actual resource utilization costs between M3T (years 2004-2007) and the previous admission-based model (2003). Average total episode costs per patient were significantly less for M3T (Australian dollars [AUD] 1,927.00, 95% confidence interval [CI] AUD 1,829.00-1,037.00) compared with the admission-based model (AUD 4,841.00, 95% CI AUD 4,178.00-5,590.00). Nonadmission care in M3T was substantially costsaving with a median 3 (95% uncertainty interval 0.7-6.0) additional strokes averted per 100 patients treated, based on an observed 90-day stroke rate of 1.50% (95% CI 0.73%-3.05%) and 4.67% (95% CI 2.28%-9.32%) in the admission-based model.Copyright © 2015 American Academy of Neurology.

Aim: Ethnic differences have been reported between Asians and Whites in the prevalence of stroke subtypes. However, it is unknown if population differences exist for manifestations of cerebral small vessel disease. We compared the prevalence and risk of white matter hypertensities (WMH), lacunes, and microbleeds between Han Chinese and White Australian individuals randomly selected from their respective populations. Method(s): Magnetic resonance imaging (1.5-Tesla) was performed on participants of the Shanghai Aging Study (n = 321, mean age 69 +/- 6 years) and Tasmanian Study of Cognition and Gait (n = 397, mean age 72 +/- 7 years). A single expert rater recorded measures of WMH, lacunes, and microbleeds. We also compared lesion prevalence between age- and gender-matched subgroups from the two cohorts. Among all subjects (n = 718), we performed multiple logistic regression, adjusted for putative risk factors, to examine if ethnicity was independently associated with these lesions. Result(s): The prevalence rates of confluent WMH, lacunes, and microbleeds among Chinese and Whites were 37% vs. 34% (p = 0.09), 29% vs. 34% (p = 0.24) and 9% vs. 11% (p = 0.59), respectively. Subgroup analysis among age- and gender-matched subjects showed that confluent WMH was significantly more common among Chinese (38.5%) than Whites (28.4%, p = 0.01). In multiple logistic regression, Chinese ethnicity was associated with a higher risk of confluent WMH (odds ratio 1.7, 95% confidence interval 1.1-2.6, p = 0.01). No differences were seen for lacunes and microbleeds. Conclusion(s): In this population-based cross-national comparison, Han Chinese had a greater risk of confluent WMH than White Australians, but a similar risk of lacunes and microbleeds.