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Background: Gerontology and ageing research are increasingly focussing on healthy life span (healthspan), the period of life lived free of serious disease and disability. Late-life depression (LLD) is believed to impact adversely on physical health. However, no studies have examined its effect on healthspan. This study investigated the effect of LLD and subthreshold depression on disability-free survival, a widely accepted measure of healthspan. Methods: This prospective cohort study used data from the ASPirin in Reducing Events in the Elderly study. Participants were aged ≥70 years (or ≥65 years for African-American and Hispanic participants) and free of dementia, physical disability and cardiovascular disease. Depressive symptoms were measured using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10). LLD and subthreshold depression were defined as CES-D-10 scores ≥8 and 3–7, respectively. Disability-free survival was defined as survival free of dementia and persistent physical disability. Results: A total of 19,110 participants were followed up for a maximum of 7.3 years. In female participants, LLD was associated with lower disability-free survival adjusting for sociodemographic and lifestyle factors, medical comorbidities, polypharmacy, physical function and antidepressant use (HR, 1.50; 95% CI, 1.23–1.82). In male participants, LLD was associated with lower disability-free survival adjusting for sociodemographic and lifestyle factors (HR, 1.30; 95% CI, 1.03–1.64). Subthreshold depression was also associated with lower disability-free survival in both sexes. Conclusions: LLD may be a common and important risk factor for shortened healthspan.

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.82; 95% CI 1.30–2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.64; 95% CI 1.26–2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk. Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.

With the progressive aging of the world’s population, prolongation of a healthy lifespan in old age has become a medical research priority. The presence of depressive symptoms in later life is associated with poor health prognosis and increased mortality1,2. Here we explore distinct trajectories of depressive symptoms in later life and their association with several health-related outcomes in 19,110 older individuals followed for a median of 4.7 years. Using a latent class, mixed-modeling approach we identified four distinct trajectories of depressive symptoms with scoring patterns of consistently low, moderate, emerging and persistently high. Compared to those with minimal depressive symptoms, membership of any other class was associated with specific patterns of baseline sociodemographic and medical factors. Membership of any group with depressive symptoms was associated with a higher likelihood of health events, including physical disability, cancer and major bleeding episodes. Membership of the persistently depressed class was associated with increased mortality, while a diagnosis of dementia was generally limited to the class with initially low and progressively rising symptoms. The course of depressive symptoms in older individuals can vary widely and depend on several factors. The presence of depressive symptoms, including those that do not meet criteria for major depression, can flag a poor prognosis and risk for specific health conditions. Systematic assessment of depressive symptoms may facilitate early identification of at-risk populations.

Background: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. Methods: We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. Results: At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28). Conclusion: A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction f

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583).

Identification of individuals with increased risk of major adverse cardiovascular events (MACE) is important. However, algorithms specific to the elderly are lacking. Data were analysed from a randomised trial involving 18,548 participants ≥ 70 years old (mean age 75.4 years), without prior cardiovascular disease events, dementia or physical disability. MACE included coronary heart disease death, fatal or nonfatal ischaemic stroke or myocardial infarction. Potential predictors tested were based on prior evidence and using a machine-learning approach. Cox regression analyses were used to calculate 5-year predicted risk, and discrimination evaluated from receiver operating characteristic curves. Calibration was also assessed, and the findings internally validated using bootstrapping. External validation was performed in 25,138 healthy, elderly individuals in the primary care environment. During median follow-up of 4.7 years, 594 MACE occurred. Predictors in the final model included age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, serum creatinine, diabetes and intake of antihypertensive agents. With variable selection based on machine-learning, age, sex and creatinine were the most important predictors. The final model resulted in an area under the curve (AUC) of 68.1 (95% confidence intervals 65.9; 70.4). The model had an AUC of 67.5 in internal and 64.2 in external validation. The model rank-ordered risk well but underestimated absolute risk in the external validation cohort. A model predicting incident MACE in healthy, elderly individuals includes well-recognised, potentially reversible risk factors and notably, renal function. Calibration would be necessary when used in other populations.

Background: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. Methods: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. Findings: 19 114 participants with a median age of 74·0 years (IQR 71·6–77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6–5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI

Background: Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. Methods: SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography–tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. Findings: Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7–77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8–5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations

Background: General practitioners (GPs) provide ongoing support after a stroke, but little is known about these encounters and the metrics to measure them. Objective(s): To compare methods for measuring patterns of GP encounters following stroke in survival models. Method(s): We performed a landmark analysis using data from the Australian Stroke Clinical Registry (2010-2014) linked with Australian Medicare claims (2009-2016) to determine GP encounters within 18 months following stroke. Continuity of GP encounters (consistency) and regularity (distribution) were each calculated using 3 indices. Indices were compared based on 1-year survival using multivariable Cox regression models. The best performing measures of regularity and continuity, based on model fit, were combined into a composite 'optimal care' variable. Result(s): Among 10,728 registrants (43% female, 69% aged >=65 years), the median number of encounters was 17 (Q1: 10, Q3: 26) within 18 months. The measures most strongly associated with survival (hazard ratio [95% confidence interval], Akaike information criterion [AIC], Bayesian information criterion [BIC]) were the Continuity of Care Index (COCI, as a measure of continuity; 0.88 [0.76-1.02], p=0.099, AIC=13746, BIC=13855) and our persistence measure of regularity (encounter at least every 6 months; 0.80 [0.67-0.95], p=0.011, AIC=13742, BIC=13852). Our composite measure, persistence plus COCI >=80% (0.80 [0.68-0.94], p=0.008, AIC=13742, BIC=13851), performed marginally better than our persistence measure alone. Conclusion(s): GP continuity and regularity of care are important indicators of ongoing support after stroke. Our persistence measure of regularity or composite indice may be useful measures of patient outcome with respect to general practitioner encounters following stroke.

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.Copyright © 2020 International Society of Nephrology

To investigate the effect of night-time BP-lowering drug treatment on the risk of major CVD and mortality, we systematically reviewed randomized controlled trials comparing night-time versus morning dosing. Two studies were found relevant to the clinical question (the MAPEC and Hygia trials). They were similar in study design and population and were conducted by the same study group. As the Hygia trial had more power with a significantly larger sample size, we did not perform a meta-analysis. Both studies reported a reduction of ~50% in major CVD events and all-cause mortality with night-time dosing and a reduction of 60% in CVD mortality. The results from these studies support the implementation of night-time BP-lowering drug treatment in the prevention of CVD and mortality. However there is an on-going discussion on the validity and methodology of MAPEC and Hygia trials, the interpretation of the results should be cautious. Stronger evidence is needed prior to changing clinical practice. Questions that remain to be answered relate to the generalisability of the results across different populations at different levels of BP related risk and the importance of morning versus evening timing of medication on CVD prevention as determined though a well-designed randomised controlled trial.

Background and Purpose: Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. Methods: We predicted risk of incident IS events in a population of 12 792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly). The PRS was calculated using 3.6 million genetic variants. Participants had no previous history of cardiovascular events, dementia, or persistent physical disability at enrollment. The primary outcome was IS over 5 years, with stroke subtypes as secondary outcomes. A multivariable model including conventional risk factors was applied and reevaluated after adding PRS. Area under the curve and net reclassification were evaluated. Results: At baseline, mean population age was 75 years. In total, 173 incident IS events occurred over a median follow-up of 4.7 years. When PRS was added to the multivariable model as a continuous variable, it was independently associated with IS (hazard ratio, 1.41 [95% CI, 1.20-1.65] per SD of the PRS; P<0.001). The PRS alone was a better discriminator for IS events than most conventional risk factors. PRS as a categorical variable was a significant predictor in the highest tertile (hazard ratio, 1.74; P=0.004) compared with the lowest. The area under the curve of the conventional model was 66.6% (95% CI, 62.2-71.1) and after inclusion of the PRS, improved to 68.5 ([95% CI, 64.0-73.0] P=0.095). In subgroup analysis, the continuous PRS remained an independent predictor for large vessel and cardioembolic stroke subtypes but not for small vessel stroke. Reclassification was improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.17-0.43). Conclusions: PRS predicts incident IS in a healthy older population but only moderately improves prediction over conventional ri

Background β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (Type I) reactions mediated by antigen-specific IgE. Objective To identify genetic predisposing factors for immediate reactions to β-lactam antibiotics. Methods Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study (GWAS) was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort. Results GWAS identified rs71542416 within the Class II HLA region as the top hit (P = 2x10-14); this was in linkage disequilibrium with HLA-DRB1*10:01 (OR = 2.93 P = 5.4x10-7) and HLA-DQA1*01:05 (OR=2.93, P=5.4x10-7). Haplotype analysis identified that HLA-DRB1*10:01 was a risk factor even without the HLA-DQA1*01:05 allele. The association with HLA-DRB1*10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1*10:01 increased the risk of immediate hypersensitivity at a genome-wide level (OR = 2.96 P=4.1x10-9). No association with HLA-DRB1*10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams. Conclusion HLA-DRB1*10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required. Clinical implications This novel insight into the mechanisms of immediate reactions associated with penicillins may be of use in risk stratifying patients where penicillin cannot be excluded as an etiological agent.

BACKGROUND: Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both “untreated” and “treated but uncontrolled” high BP. METHODS: We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. “Controlled hypertension” was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS: Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to “treated but uncontrolled” BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). CONCLUSIONS: High levels of “untreated” and “treated but uncontrolled” BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population.

Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.

© 2020 American College of Cardiology Foundation Background: There is clinical uncertainty regarding the benefits and harms of prescribing statins in healthy subjects ≥70 years of age. Objectives: The aim of this study was to examine the association among statins, dementia-free and disability-free survival, and cardiovascular disease (CVD) among healthy older adults using data from the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods: ASPREE was a randomized trial of 19,114 community-dwelling persons in Australia and the United States ≥65 years of age and free of documented CVD, dementia, and disability. Data were collected for those ≥70 years of age, and participants who took statins at baseline were compared with those who did not using Cox proportional hazards regression with inverse probability weighting. The primary outcome, referred to as “disability-free survival,” was a composite of all-cause mortality, dementia, or persistent physical disability. Other outcomes included the individual components of the composite outcome, major adverse cardiovascular events, fatal CVD, myocardial infarction, and stroke. Results: Of the 18,096 included participants (median age 74.2 years, 56.0% women), 5,629 took statins at baseline. Over a median follow-up period of 4.7 years, baseline statin use was not associated with disability-free survival or with the risk for all-cause mortality or dementia. However, it was associated with lower risks for physical disability and all cardiovascular outcomes. Conclusions: Among healthy community-dwelling adults ≥70 years of age, statin use may be beneficial for preventing physical disability and CVD but not beneficial for prolonging disability-free survival or avoiding death or dementia. Future clinical trials are needed to confirm these findings.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. To investigate if there is evidence for a ‘legacy effect’ for blood pressure (BP) lowering treatment, that is, worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults. We systematically reviewed studies comparing the effects of delayed BP treatment (placebo/untreated during the trial or no previous treatment at trial entry) vs. early treatment (actively treated during the trial or previous BP treatment at trial entry) on mortality in the short term (5-year in-trial period) and long term (≥10 years in total period). The data were pooled using Peto ORs. A subgroup analysis by 10-year Framingham risk score was performed. Three studies (ALLHAT, Oslo and PREVEND-IT) involving 4746 participants were included. The results were heavily influenced by the ALLHAT trial. We found no significant difference in all-cause mortality between ‘delayed BP’ and ‘early treatment’ in the short-term OR 0.95 (95% CI 0.68–1.32) or long-term OR 0.90 (95% CI 0.78–1.04), with similar results for mortality from cardiovascular disease (CVD). The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD. The review showed no clinically adverse ‘legacy effect’ on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over. The results were consistent for all CVD risk subgroups. Although these studies are non-randomised post-hoc analyses, they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention populations.

© 2020 The American Geriatrics Society OBJECTIVES: To investigate the association between depressive symptoms and several medical morbidities, and their combination, in a large older population. DESIGN: Cross-sectional study of baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. SETTING: Multicentric study conducted in Australia and the United States. PARTICIPANTS: A total of 19,110 older adults (mean age = 75 years [standard deviation = ±4.5]). MEASUREMENTS: Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D 10) scale. Medical morbidities were defined according to condition-specific methods. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to test associations before and after accounting for possible confounders. RESULTS: Depressive symptoms were significantly associated with obesity (OR = 1.19; 95% CI = 1.07-1.32), diabetes (OR = 1.22; 95% CI = 1.05-1.42), gastroesophageal reflux disease (GERD) (OR = 1.41; 95% CI = 1.28-1.57), metabolic syndrome (OR = 1.16; 95% CI = 1.03-1.29), osteoarthritis (OR = 1.41; 95% CI = 1.27-1.57), respiratory conditions (OR = 1.25; 95% CI = 1.10-1.42), history of cancer (OR = 1.19; 95% CI = 1.05-1.34), Parkinson’s disease (OR = 2.56; 95% CI = 1.83-3.56), polypharmacy (OR = 1.60; 95% CI = 1.44-1.79), and multimorbidity (OR = 1.29; 95% CI = 1.12-1.49). No significant association was observed between depressive symptoms and hypertension, chronic kidney disease, dyslipidemia, and gout (P >.05). A significant dose-response relationship was evident between the number of medical comorbidities and the prevalence of depression (OR = 1.18; 95% CI = 1.13-1.22). CONCLUSION: Late-life depressive symptoms are significantly associated with several medical morbidities, and there appears to be a cumulative effect of the number of somatic diseases on the prevalence of depression. These findings augment the evidence for a complex relat

© 2020 American Medical Association. All rights reserved. Importance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression. Objective: To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults. Design, Setting, and Participants: This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included. Interventions: Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years. Main Outcomes and Measures: The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale. Results: Of the 19114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in

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 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

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

Aim: The prevalence of chronic kidney disease (CKD) in the elderly is controversial because age-related decline in kidney function may not truly reflect underlying kidney disease. We estimate the baseline prevalence and predictors of CKD using the CKD Epidemiology Collaboration (CKD-EPIeGFR) and Berlin Initiative Study 1 (BIS1eGFR) eGFR equations in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. Method(s): GFR was estimated using CKD-EPI and BIS1 equations. CKD was defined as eGFR <60 mL/min/1.73 m2 or >= 60 mL/min/1.73 m2 with urine albumin creatinine ratio (UACR) >= 3 mg/mmol. Logistic regression was used to identify predictors of CKD prevalence defined by each eGFR equation. Result(s): Data for analysis were complete for 17,762 participants. Mean age was 75.1 years (SD 5); 56.4% were female, 76.4% had hypertension, 9% had diabetes mellitus. Mean CKD-EPIeGFR was 73.0 (SD 14.2), compared with mean BIS1eGFR of 62.7 (11.4). Median UACR was 0.8 (IQR 0.5, 1.5) mg/mmol. Prevalence of CKD by CKD-EPIeGFR was 27% (predominantly due to normoalbuminuric stage 3a CKD), substantially lower than 47.1% by BIS1eGFR; the difference was predominantly driven by reclassification of individuals from G1 and G2 CKD to stage G3a without albuminuria. Increased prevalence of CKD by either equation was related to older age, hypertension, diabetes, or higher body mass index. Conclusion(s): Prevalence of CKD with CKD-EPIeGFR was 27%, and doubled using the elderly specific BIS1eGFR, with most participants reclassified from stage 2 to stage 3a. Increased prevalence of CKD was related older age, hypertension, diabetes, or increased body mass index.Copyright © 2019 Asian Pacific Society of Nephrology

Background: Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results: We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: −0.37±1.95; 95% CI, −0.54 to −0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions: Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

© 2019 The Author(s). Background: Large-scale studies risk generating inaccurate and missing data due to the complexity of data collection. Technology has the potential to improve data quality by providing operational support to data collectors. However, this potential is under-explored in community-based trials. The Aspirin in reducing events in the elderly (ASPREE) trial developed a data suite that was specifically designed to support data collectors: the ASPREE Web Accessible Relational Database (AWARD). This paper describes AWARD and the impact of system design on data quality. Methods: AWARD's operational requirements, conceptual design, key challenges and design solutions for data quality are presented. Impact of design features is assessed through comparison of baseline data collected prior to implementation of key functionality (n = 1000) with data collected post implementation (n = 18,114). Overall data quality is assessed according to data category. Results: At baseline, implementation of user-driven functionality reduced staff error (from 0.3% to 0.01%), out-of-range data entry (from 0.14% to 0.04%) and protocol deviations (from 0.4% to 0.08%). In the longitudinal data set, which contained more than 39 million data values collected within AWARD, 96.6% of data values were entered within specified query range or found to be accurate upon querying. The remaining data were missing (3.4%). Participant non-attendance at scheduled study activity was the most common cause of missing data. Costs associated with cleaning data in ASPREE were lower than expected compared with reports from other trials. Conclusions: Clinical trials undertake complex operational activity in order to collect data, but technology rarely provides sufficient support. We find the AWARD suite provides proof of principle that designing technology to support data collectors can mitigate known causes of poor data quality and produce higher-quality data. Health information technology (IT) produc

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: To estimate the prevalence of non-communicable disease (NCD) risk factors at a provincial level in Vietnam, and to assess whether the summary estimates allow reliable inferences to be drawn regarding regional differences in risk factors and associations between them. METHODS: Participants (n=14706, 53.5 % females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Data were analysed using complex survey methods. RESULTS: Differences by sex in mean years of schooling (males 8.26+/-0.20, females 7.00+/-0.18), proportions of current smokers (males 57.70 %, females 1.73 %), and binge-drinkers (males 25.11 %, females 0.63 %), and regional differences in diet, reflected the geographical and socio-cultural characteristics of the country. Provinces with a higher proportion of urban population had greater mean levels of BMI (r=0.82), and lesser proportions of active people (r=-0.89). The associations between the summary estimates were generally plausible (e.g. physical activity and BMI, r=-0.80) but overstated, and with some anomalous findings due to characterisation of smoking and hypertension by STEPS protocols. CONCLUSIONS: This report provides an extensive description of the sex-specific and regional distribution of NCD risk factors in Vietnam and an account of some health-related consequences of industrialisation in its early stages. The STEPS protocols can be utilized to provide aggregate data for valid between-population comparisons, but with important caveats identified.

Objective Provision of a discharge care plan and prevention therapies is often suboptimal. Our objective was to design and pilot test an interdisciplinary, organisational intervention to improve discharge care using stroke as the case study using a mixed-methods, controlled before-after observational study design. Setting Acute care public hospitals in Queensland, Australia (n=15). The 15 hospitals were ranked against a benchmark based on a composite outcome of three discharge care processes. Clinicians from a 'top-ranked' hospital participated in a focus group to elicit their success factors. Two pilot hospitals then participated in the organisational intervention that was designed with experts and consumers. Participants Hospital clinicians involved in discharge care for stroke and patients admitted with acute stroke or transient ischaemic attack. Intervention A four-stage, multifaceted organisational intervention that included data reviews, education and facilitated action planning. Primary and secondary outcome measures Three discharge processes collected in Queensland hospitals within the Australian Stroke Clinical Registry were used to select study hospitals: (1) discharge care plan; (2) antihypertensive medication prescription and (3) antiplatelet medication prescription (ischaemic events only). Primary measure: Composite outcome. Secondary measures: Individual adherence changes for each discharge process; sensitivity analyses. The performance outcomes were compared 3 months before the intervention (preintervention), 3 months postintervention and at 12 months (sustainability). Results Data from 1289 episodes of care from the two pilot hospitals were analysed. Improvements from preintervention adherence were: Antiplatelet therapy (88%vs96%, p=0.02); antihypertensive prescription (61%vs79%, p<0.001); discharge planning (72%vs94%, p<0.001); composite outcome (73%vs89%, p<0.001). There was an insignificant decay effect over the 12-month sustainability period (com

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

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.

Aims: To provide nationally representative data on alcohol consumption in Vietnam and to assess whether reported numbers of 'standard drinks' consumed have evidence of validity (particularly in rural areas where home-made alcohol is consumed from cups of varying size). Method(s): A nationally representative population-based survey of 14,706 participants (46.5% males, response proportion 64.1%) aged 25-64 years in Vietnam. Measurements were made in accordance with WHO STEPS protocols. Data were analysed using complex survey methods. Result(s): Among men, 80% reported drinking alcohol during the last year, and 40% were hazardous/harmful drinkers. Approximately 60% of men and <5% of women had consumed alcohol during the last week, with one-in-four of the men reporting having consumed at least five standard drinks on at least one occasion. Numbers of standard drinks reported by men were associated with blood pressure/hypertension, particularly in rural areas (P < 0.001 for trend). Most of the calibration and discrimination possible from self-reported information on alcohol consumption was provided by binary responses to questions on whether or not alcohol had been consumed during the reference period. Conclusion(s): Alcohol use and harmful consumption were common among Vietnamese men but less pronounced than in Western nations. Self-reports of quantity of alcohol consumed in terms of standard drinks had predictive validity for blood pressure and hypertension even in rural areas. However, using detailed measures of consumption resulted in only minor improvements in prediction compared to simple measures.Copyright © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

There are many recommended pharmacotherapies and lifestyle changes that are used to manage risk factors and, in turn, reduce the risk of recurrent stroke. Although these therapies and lifestyle changes are often initiated shortly after stroke, once patients are at home there are challenges when sustaining the use of these therapies and lifestyle changes over the longer term. The aim of this educational workshop is to discuss current opportunities to manage the prevention of recurrent stroke in the community, ensure improved communication with general practitioners and support greater awareness of the risk of stroke. Examples of effective interdisciplinary models of care and the importance of effective discharge care planning and patient self-management will be covered.

The aims of the present study were to provide nationally representative data on fruit and vegetable consumption in Vietnam, and to assess the accuracy of the reported numbers of 'standard servings' consumed. Data analysed were from a multi-stage stratified cluster survey of 14 706 participants (46.5 % males, response proportion 64.1 %) aged 25-64 years in Vietnam. Measurements were made in accordance with the WHO STEPwise approach to surveillance of non-communicable diseases (STEPS) protocols. Approximately 80 % of Vietnamese people reported having less than five servings of fruit and vegetables daily in a typical week. Fruit and vegetable intake reported in 'standard serving' sizes was positively correlated with levels of education completed and household income (P<0.001 for trend). The correlations between summary values for each province reflect some known demographic, geographical and climatic characteristics of the country. For example, provinces at higher latitude had higher mean servings of vegetables (r 0.90), and provinces with higher proportions of urban population had higher mean servings of fruit (r 0.40). In conclusion, about eight in ten Vietnamese people aged 25-64 years did not meet WHO recommendations for daily consumption of at least five servings of fruit and vegetables. On the basis of the consistency of the data collected with other estimates and with physical and demographic characteristics of the country, the WHO STEPS instrument has construct validity for measuring fruit and vegetable intake, but with two issues identified. The issues were seasonal variation in reporting and a limitation on the usefulness of the information for associative analyses.Copyright © The Authors 2016.

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.

XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective XPG mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known about how XPG loss results in this devastating disease. We identify XPG as a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR). XPG depletion causes DNA double-strand breaks, chromosomal abnormalities, cell-cycle delays, defective HRR, inability to overcome replication fork stalling, and replication stress. XPG directly interacts with BRCA2, RAD51, and PALB2, and XPG depletion reduces their chromatin binding and subsequent RAD51 foci formation. Upstream in HRR, XPG interacts directly with BRCA1. Its depletion causes BRCA1 hyper-phosphorylation and persistent chromatin binding. These unexpected findings establish XPG as an HRR protein with important roles in genome stability and suggest how XPG defects produce severe clinical consequences including cancer and accelerated aging. It is unclear how the loss of XPG protein causes the neurodevelopmental disorder Cockayne syndrome with death in early childhood. Trego et al. show that XPG partners with BRCA1 and BRCA2 to maintain genomic stability through homologous recombination, and its loss causes DNA breaks, chromosome aberrations, and replication fork stalling.

There are many recommended pharmacological and non-pharmacological therapies for the prevention of stroke, and an ongoing challenge is to improve their uptake. Personalized medicine is seen as a possible solution to this challenge. Although the use of genetic information to guide health care could be considered as the apex of personalized medicine, genetics is not yet routinely used to guide prevention of stroke. Currently personalized aspects of prevention of stroke include tailoring interventions based on global risk, the utilization of individualized management plans within a model of organized care, and patient education. In this review we discuss the progress made in these aspects of prevention of stroke and present a case study to illustrate the issues faced by health care providers and patients with stroke that could be overcome with a personalized approach to the prevention of stroke.Copyright © 2015 Kim et al.

Introduction: To supplement limited information on tobacco use in Vietnam, data from a nationally-representative population-based survey was used to estimate the prevalence of smoking among 25-64 year-olds. Method(s): This study included 14,706 participants (53.5% females, response proportion 64%) selected by multi-stage stratified cluster sampling. Information was collected using the World Health Organization STEPwise approach to surveillance of risk factors for non-communicable disease (STEPS) questionnaire. Smoking prevalence was estimated with stratification by age, calendar year, and birth year. Result(s): Prevalence of ever-smoking was 74.9% (men) and 2.6% (women). Male ever-smokers commenced smoking at median age of 19.0 (interquartile range [IQR]: 17.0, 21.0) years and smoked median quantities of 10.0 (IQR: 7.0, 20.0) cigarettes/day. Female ever-smokers commenced smoking at median age of 20.0 (IQR: 18.0, 26.0) years and smoked median quantities of 6.0 (IQR: 4.0, 10.0) cigarettes/day. Prevalence has decreased in recent cohorts of men (p = .001), and its inverse association with years of education (p < .001) has strengthened for those born after 1969 (interaction p < .001). At 60 years of age, 53.0% of men who had reached that age were current smokers and they had accumulated median exposures of 39.0 (IQR: 32.0, 42.0) years of smoking and 21.0 (IQR: 11.5, 36.0) pack-years of cigarettes. The proportion of ever-smokers has decreased consistently among successive cohorts of women (p < .001). Conclusion(s): Smoking prevalence is declining in recent cohorts of men, and continues to decline in successive cohorts of women, possibly in response to anti-tobacco initiatives commencing in the 1990s. Low proportions of quitters mean that Vietnamese smokers accumulate high exposures despite moderate quantities of cigarettes smoked per day.Copyright © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rig

Introduction: Our aims were to provide the first national estimates of physical activity (PA) for Vietnam, and to investigate issues affecting their accuracy. Method(s): Measurements were made using the Global Physical Activity Questionnaire (GPAQ) on a nationally-representative sample of 14706 participants (46.5% males, response 64.1%) aged 25-64 years selected by multi-stage stratified cluster sampling. Result(s): Approximately 20% of Vietnamese people had no measureable PA during a typical week, but 72.9%(men) and 69.1% (women) met WHO recommendations for PA by adults for their age. On average, 52.0 (men) and 28.0 (women) Metabolic Equivalent Task (MET)-hours/week (largely from work activities) were reported. Work and total PA were higher in rural areas and varied by season. Less than 2% of respondents provided incomplete information, but an additional one-in-six provided unrealistically high values of PA. Those responsible for reporting errors included persons from rural areas and all those with unstable work patterns. Box-Cox transformation (with an appropriate constant added) was the most successful method of reducing the influence of large values, but energy-scaled values were most strongly associated with pathophysiological outcomes. Conclusion(s): Around seven-in-ten Vietnamese people aged 25-64 years met WHO recommendations for total PA, which was mainly from work activities and higher in rural areas. Nearly all respondents were able to report their activity using the GPAQ, but with some exaggerated values and seasonal variation in reporting. Data transformation provided plausible summary values, but energy-scaling fared best in association analyses. Copyright:Copyright © 2015 Bui et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Comprehensive community care has the potential to improve risk factor management of patients with stroke or transient ischaemic attack. Aim(s): The primary aim is to determine the effectiveness of an individualized management program on risk factor management for patients discharged from hospital after stroke. Design(s): Multicentre, cluster-randomized, controlled trial, with clusters by general practice. Participants are randomized to receive intervention or control after a baseline assessment undertaken after discharge from hospital. The general practice they attend is marked as an intervention or control accordingly. All subsequent participants attending those practices are automatically assigned as intervention or control. Baseline and all outcome assessments, including an analysis of risk factors, are undertaken by assessors blinded to patient randomization. Intervention Details: Based on the results of blinded assessments, the individualized management program group will receive targeted advice on how to manage their risk factors using a standardized, evidence-based template to communicate 'ideal' management with their general practitioner. In addition, patients randomized to the individualized management program group will receive counselling and education about stroke risk factor management by an intervention study nurse. Individualized management programs will be reviewed at three-months, six-months, 12 months, and 18 months after stroke, at which times they will be modified if appropriate. Stroke risk management will be evaluated using changes in the Framingham cardiovascular risk score. Analysis will be on an intention-to-treat basis using analysis of covariance or generalized linear model to adjust for baseline risk score and other relevant confounding factors. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Introduction: Adherence to secondary prevention recommendations vary. Audit and feedback may be used as an effective means of changing clinician behaviour in general practice. Aim(s): To investigate the usefulness of audit and feedback to improve secondary stroke prevention in primary care. Method(s): General practitioners (GPs) involved in the intervention arm of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management (STAND FIRM) randomised controlled trial were invited to participate in an education activity on stroke. GPs attended a seminar on secondary stroke prevention and then were instructed to identify 20 patients with a history of stroke/ TIA in their general practice. The GPs documented stroke risk factors, and the pharmacological and non-pharmacological treatments prescribed to the patients they identified. As an educational reinforcing activity, the participating GPs were instructed to comment on how the management of the audited patients could be improved. Result(s): Six of 14 GPs attending the seminar participated in the clinical audit, providing data for 101 patients. Prescription rates in these patients were 83% for antihypertensives, 79% for antithrombotics, and 75% for cholesterol-lowering medications. Two GPs provided comments on how the management of their 40 audited patients might be improved. These GPs indicated that in 9/40 patients, they would consider prescribing a new prevention medication. Other changes suggested by GPs included: checking medication adherence and providing advice on lifestyle changes. Conclusion(s): Comprehensive education activities permit reflection on clinical practice. GPs identified many areas of their secondary prevention management that could be improved.

BACKGROUND:: Lowering blood pressure after stroke reduces the risk of recurrent stroke and other vascular events. However, there is recent evidence that low blood pressure may also result in poor outcome. For the first time, this study aimed to investigate the relationship between blood pressure and outcome in long-term survivors of stroke. METHOD(S):: Participants from the North East Melbourne Stroke Incidence Study were contacted at 5 years after stroke for a follow-up assessment. Blood pressure was measured according to a strict protocol. A multivariable Cox proportional hazards regression model was used to assess the association between SBP measurements at 5 years after stroke and outcome (death, acute myocardial infarction or recurrent stroke) to 10 years after stroke. RESULT(S):: In 5-year survivors of stroke, compared to a SBP of 131-141 mmHg, a SBP of 120 mmHg or less was associated with a 61% greater risk of stroke, acute myocardial infarction and death (hazard ratio 1.61, 95% confidence interval 1.08-2.41, P=0.019). Compared to the reference category of SBP 131-141 mmHg, there were no differences in outcome in the patients with SBP 121-130 mmHg (P=0.491) or 142-210 mmHg (P=0.313). These findings were not modified when adjusting for prescription of antihypertensive medications. CONCLUSION(S):: There was a greater risk of poor outcome in long-term survivors of stroke with low SBP. This is further evidence that low SBP may result in poor prognosis. Ideal blood pressure levels for long-term survivors of stroke may need to be reassessed. Copyright © Lippincott Williams & Wilkins.