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Background: Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims: To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke) and again at follow-up (6 months). Methods & Procedures: This study compared two cohorts from successive studies conducted in four Australian acute/sub-acute hospitals. The studies had near identical recruitment, blinded assessment and data-collection protocols. The Very Early Rehabilitation (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions of impairment-based aphasia therapy, up to 5 weeks. The control cohort (n = 27) also had mild-severe aphasia and received usual care (UC) therapy for up to 4 weeks post-stroke. The primary outcome measure was the Aphasia Quotient (AQ) and a measure of communicative efficiency (DA) at therapy completion. Outcomes were measured at baseline, therapy completion and 6 months post-stroke and were compared using Generalised Estimating Equations (GEE) models. Outcomes & Results: After controlling for initial aphasia and stroke disability, the GEE models demonstrated that at the primary end-point participants receiving VER achieved 18% greater recovery on the AQ and 1.5% higher DA scores than those in the control cohort. At 6 months, the VER participants maintained a 16% advantage in recovery on the AQ and 0.6% more on DA scores over the control cohort participants. Conclusions & Implications: A prescribed, impairment-based aphasia therapy regimen, provided daily in very early post-stroke recovery, resulted in significantly greater communication gains in people with mild-severe aphasia at completion of therapy and at 6 months, when compared with a historical control cohort. Further research is required to demonstrate large-scale and long-term efficacy.

Background: The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.Objective: To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.Design: Cohort study.Setting: UK Biobank prospective cohort.Participants: Community-dwelling men aged 40 to 69 years.Measurements: Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.Results: Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).Limitation: Observational study; single baseline measurement of testosterone and SHBG.Conclusion: Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.Primary Funding Source: Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Effectiveness of early intensive aphasia rehabilitation after stroke is unknown. The Very Early Rehabilitation for SpEech trial (VERSE) aimed to determine whether intensive aphasia therapy, beginning within 14 days after stroke, improved communication recovery compared to usual care. Methods: Prospective, randomized, single-blinded trial conducted at 17 acute-care hospitals across Australia/New Zealand from 2014 to 2018. Participants with aphasia following acute stroke were randomized to receive usual care (direct usual care aphasia therapy), or one of two higher intensity regimens (20 sessions of either non-prescribed (usual care-plus or prescribed (VERSE) direct aphasia therapy). The primary outcome was improvement of communication on the Western Aphasia Battery-Revised Aphasia Quotient (AQ) at 12 weeks after stroke. Our pre-planned intention to treat analysis combined high intensity groups for the primary outcome. Findings: Among 13,654 acute stroke patients screened, 25% (3477) had aphasia, of whom 25% (866) were eligible and 246 randomized to usual care (n = 81; 33%), usual care-plus (n = 82; 33%) or VERSE (n = 83; 34%). At 12 weeks after stroke, the primary outcome was assessed in 217 participants (88%); 14 had died, 9 had withdrawn, and 6 were too unwell for assessment. Communication recovery was 50.3% (95% CI 45.7–54.8) in the high intensity group (n = 147) and 52.1% (95% CI 46.1–58.1) in the usual care group (n = 70; difference −1.8, 95% CI −8.7–5.0). There was no difference between groups in non-fatal or fatal adverse events (p = 0.72). Interpretation: Early, intensive aphasia therapy did not improve communication recovery within 12 weeks post stroke compared to usual care. [ABSTRACT FROM AUTHOR]

The National Heart Foundation of Australia has updated the Guide to management of hypertension 2008: assessing and managing raised blood pressure in adults (updated December 2010). Main recommendations For patients at low absolute cardiovascular disease risk with persistent blood pressure (BP) ≥ 160/100 mmHg, start antihypertensive therapy. The decision to treat at lower BP levels should consider absolute cardiovascular disease risk and/or evidence of end-organ damage, together with accurate BP assessment. For patients at moderate absolute cardiovascular disease risk with persistent systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, start antihypertensive therapy. Treat patients with uncomplicated hypertension to a target BP of < 140/90 mmHg or lower if tolerated. Changes in management as a result of the guideline Ambulatory and/or home BP monitoring should be offered if clinic BP is ≥ 140/90 mmHg, as out-of-clinic BP is a stronger predictor of outcome. In selected high cardiovascular risk populations, aiming for a target of < 120 mmHg systolic can improve cardiovascular outcomes. If targeting < 120 mmHg, close follow-up is recommended to identify treatment-related adverse effects including hypotension, syncope, electrolyte abnormalities and acute kidney injury. Why the changes have been made A 2015 meta-analysis of patients with uncomplicated mild hypertension (systolic BP range, 140-169 mmHg) demonstrated that BP-lowering therapy is beneficial (reduced stroke, cardiovascular death and all-cause mortality). A 2015 trial comparing lower with higher blood pressure targets in selected high cardiovascular risk populations found improved cardiovascular outcomes and reduced mortality, with an increase in some treatment-related adverse events. [ABSTRACT FROM AUTHOR]

Background: The incidence of traumatic brain injury (TBI) is rising, as are its neuropsychiatric complications. This study aims to determine (1) the prevalence of TBI, (2) the association between history of past TBI and sociodemographic, lifestyle and clinical factors, and (3) the risk of depression and cognitive impairment in later life associated with exposure to TBI.Methods: Cross-sectional study of a community-derived sample of 5486 Australian men aged 70-89 years. Information on TBI was retrieved from the Western Australian Data Linkage System (WADLS) and via self-report. We used the WADLS and self-report to ascertain history of past depression, and the Geriatric Depression Scale 15-items to assess current clinically significant symptoms of depression, defined by score ≥7. We defined cognitive impairment by a mini-mental state examination score <24 or a WADLS diagnosis of dementia.Results: Nine hundred fifty-three men had history of TBI (17.4%). Factors associated with TBI included coronary heart disease, stroke, poor self-perceived physical health and falls. TBI increased the odds ratio of past (odds ratio (OR) = 1.55, 95% confidence interval (CI) = 1.21, 1.99) and current depression (OR = 1.77, 95% CI = 1.36, 2.32), as well as of cognitive impairment (OR = 1.23, 95% CI = 1.00, 1.51). The population fractions of depression and cognitive impairment attributable to TBI were 6.9% (95% CI = 3.3%, 10.3%) and 3.4% (95% CI = 0.0%, 6.9%).Conclusions: History of TBI is common in older men, and is associated with increased risk of depression and cognitive impairment. If this association is truly causal, then the effective reduction of events leading to TBI (e.g., motor vehicle accidents and falls) may also decrease the prevalence of depression and cognitive impairment in later life. [ABSTRACT FROM AUTHOR]

Decline in linguistic function has been associated with decline in cognitive function in previous research. This research investigated the informativeness of written language samples of Australian men from the Health in Men's Study (HIMS) aged from 76 to 93 years using the Computerised Propositional Idea Density Rater (CPIDR 5.1). In total, 60 255 words in 1147 comments were analysed using a linear-mixed model for statistical analysis. Results indicated no relationship with education level ( p = 0.79). Participants for whom English was not their first learnt language showed Propositional Idea Density (PD) scores slightly lower (0.018 per 1 word). Mean PD per 1 word for those for whom English was their first language for comments below 60 words was 0.494 and above 60 words 0.526. Text length was found to have an effect ( p = <0.0001). The mean PD was higher than previously reported for men and lower than previously reported for a similar cohort for Australian women. [ABSTRACT FROM AUTHOR]

Background and Aim The effects of very early aphasia therapy on recovery are equivocal. This article examines predictors of very early aphasia recovery through statistical modeling. Methods This study involved a secondary analysis of merged data from two randomized, single-blind trials conducted in Australian acute and subacute hospitals. Study 1 (n = 59) compared daily therapy to usual ward care for up to 4 weeks poststroke in patients with moderate to severe aphasia. Study 2 (n = 20) compared daily group therapy to daily individual therapy for 20 1-hour sessions over 5 weeks, in patients with mild to severe aphasia. The primary outcome measure was the Western Aphasia Battery Aphasia Quotient (AQ) at therapy completion. This analysis used regression modeling to examine the effects of age, baseline AQ and baseline modified Rankin Scale (mRS), average therapy amount, therapy intensity, and number of therapy sessions on aphasia recovery. Results Baseline AQ (p = 0.047), average therapy amount (p = 0.030), and baseline mRS (p = 0.043) were significant predictors in the final regression model, which explained 30% (p < 0.001) of variance in aphasia recovery. Conclusion The amount of very early aphasia therapy could significantly affect communication outcomes at 4 to 5 weeks poststroke. Further studies should include amount of therapy provided to enhance reliability of prognostic modeling in aphasia recovery. [ABSTRACT FROM AUTHOR]

Objectives: To examine temporal trends in the incidence and recurrence of hospitalised coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD) separately and combined, and by the history of all forms of atherothrombotic disease (ATD). Design: Population-based longitudinal data linkage study. Setting Western Australia. Participants: All patients aged 35e84 years hospitalised in Western Australia for CHD, CeVD or PAD from 2000 to 2007. Main Outcome Measures: Age-standardised incidence and recurrence rates of CHD, CeVD and PAD stratified by ATD history, sex and age. Results: 107 576 events (65.9% men) were identified; 70% of all admissions were for CHD. In patients without a history of any ATD, incidence rates declined significantly in all groups, although the reduction in incident CHD in women was marginal (0.7%/year, 95% CI 1.5 to +0.1%). The largest annual reductions in incidence rates were for PAD (men, 6.4%/year, 95% CI 7.7 to 5.0%; women, 5.4%/year, 95% CI 7.2 to 3.6%) and CeVD in women (4.0%/year, 95% CI 5.0 to 3.0%). Falls in overall recurrence rates were greatest for CeVD (men, 3.2%/year, 95% CI 4.7 to 1.6%; women 4.6%/year, 95% CI 6.4 to 2.7%). Trends across all categories of polyvascular ATD were generally downward, although not all changes were statistically significant. Conclusion: The incidence and recurrence rates of hospitalised ATD have decreased over time, including in patients with disease involving multiple vascular territories. This implies that primary and secondary prevention strategies have been broadly effective. However, high absolute rates of recurrence and limited reduction in 35e54-year-old individuals highlight patient groups to target to reduce further the burden of ATD. [ABSTRACT FROM AUTHOR]

The article presents a debate on whether adult patients in Australia should be routinely tested for heritable thrombophilia after an episode of venous thromboembolism (VTE). It discusses the need for local evidence-based guidelines that take into account the prevalence of heritable thrombophilia, and the availability of population norms to guide interpretation of test results. The validity of the test result and the evaluation of clinical risk factors are also considered.

The article presents the results of a pooled analysis of the socioeconomic disparities in stroke rates and outcome in Australia and New Zealand. The researchers analysed the pooled data for 3077 patients with incident stroke from three population-based studies in Perth, Melbourne, and Auckland between 1995 and 2003. The results of the analysis indicate that people living in areas that are relatively more deprived in socioeconomic terms have higher rates of stroke.

Background: Sleep difficulties increase the risk of current and future depression, but it is unclear if this relationship is causal.Methods: Prospective cohort study of a community sample of men aged 70-89 years followed for up to 17 years. Initial assessments occurred between 2001 and 2004. Participants were followed until death or 31 December 2018. Patient Health Questionnaire (PHQ-9) ≥ 10 at subsequent waves of assessments (every 2-3 years) or the recorded diagnosis of a depressive disorder in the Western Australian Data Linkage System marked the onset of depression during follow up. We excluded from follow up men with prevalent depression. The systematic review of longitudinal studies examining the association between disrupted sleep and depression in later life followed PRISMA guidelines.Results: 3441 of 5547 older men reported sleep difficulties at study entry. Current or past depression affected 437 of 5547 participants. Of the 4561 older men free of depression, 2693 reported sleep difficulties. The hazard ratio (HR) of incident depression among participants with sleep problems was 1.67 (95%CI = 1.39-2.00). Statistical adjustments for age, place of birth, education, smoking and physical frailty did not change the effect-size of this association. The systematic review identified another 14 studies, and the meta-analysis yielded an overall risk ratio of depression of 1.82 (95%CI = 1.69-1.97), although the overall quality of available evidence was sub-optimal.Conclusions: Disrupted sleep increases the risk of depression in later life and this seems unlikely to be due to reverse causality. Older adults with sleep difficulties are legitimate targets of interventions to prevent depression. [ABSTRACT FROM AUTHOR]

Aims: We examined associations of ferritin and 25-hydroxyvitamin D with fasting glucose and prevalent diabetes in older men.Methods: Cross-sectional analysis of 4153 community-dwelling men aged 70 to 89 years in Western Australia. Plasma ferritin, 25-hydroxyvitamin D, and glucose were assayed. Diabetes was ascertained from self-report, medications, and fasting glucose.Results: There were 577 men with diabetes (13.9%). In the whole cohort, ferritin was associated with fasting glucose (0.051 mmol/L per 1 SD increase in ferritin, P = .006) and 25-hydroxyvitamin D was inversely associated (-0.085 mmol/L per 1 SD, P < .001). Ferritin was not associated with prevalent diabetes (highest vs. lowest quartile; >225 vs <66 μg/L: adjusted odds ratio [OR] 0.97, 95% confidence interval [CI], 0.74-1.27, P = .83). Higher vitamin D was associated with decreased odds of prevalent diabetes (highest vs lowest quartile; >82 nmol/L vs <53 nmol/L: OR = 0.57, 95% CI = 0.43-0.75, P < .001). There was no interaction between ferritin and vitamin D on diabetes risk.Conclusions: In older men, ferritin is associated with fasting glucose but not prevalent diabetes. Higher 25-hydroxyvitamin D concentrations are independently associated with lower fasting glucose and reduced risk of diabetes. Clinical trials are required to determine whether interventions, which raise vitamin D concentrations, would reduce incidence of diabetes in this expanding demographic group. [ABSTRACT FROM AUTHOR]

The article focuses on a study that was conducted to investigate the efficacy of endovascular therapy after intravenous tissue plasminogen activator (t-PA) versus t-PA alone for stroke. The study randomly assigned patients who had received intravenous t-PA to receive additional endovascular therapy or intravenous t-PA alone. The results of the study showed safety outcomes after intravenous t-PA, as compared with intravenous t-PA alone.

Objective: To determine if hearing loss is associated with increased risk of frailty in later life.Study Design: Cross-sectional study of a community sample of 4,004 men aged 70 years and above living in the metropolitan region of Perth, Western Australia. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). Frailty was assessed using the FRAIL scale and the Frailty Index. Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. We also collected demographic, lifestyle and social support information.Main Outcome Measures: Frailty was assessed using the FRAIL scale and the Frailty Index.Results: The prevalence of frailty in the sample population was 16.1% and 25.4% when assessed using the FRAIL scale and the Frailty Index respectively. After adjusting for participant demographic, lifestyle and social factors, hearing loss was significantly associated with the prevalence of frailty when diagnosed by either measure (FRAIL scale: odds ratio [OR] 1.59, 95 CI% 1.32 to 1.91; Frailty Index: OR 1.76, 95 CI% 1.50 to 2.05). The proportion of men with hearing loss increased with increasing severity of frailty.Conclusion: Hearing loss is associated with increased prevalence of frailty in older men when assessed using the FRAIL scale and the Frailty Index. Future longitudinal studies using objective measures of hearing will be helpful in determining if this association is likely to be causal. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.Methods: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.Findings: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).Interpretation: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. [ABSTRACT FROM AUTHOR]

Objective Hospitalization for atrial fibrillation (AF) is a large and growing public health problem. We examined current trends in the incidence, prevalence, and associated mortality of first-ever hospitalization for AF. Methods Linked hospital admission data were used to identify all Western Australia residents aged 35–84 years with prevalent AF and incident (first-ever) hospitalization for AF as a principal or secondary diagnosis during 1995–2010. Results There were 57,552 incident hospitalizations, mean age 69.8 years, with 41.4% women. Over the calendar periods, age- and sex-standardized incidence of hospitalization for AF as any diagnosis declined annually by 1.1% (95% CI; 0.93, 1.29), while incident AF as a principal diagnosis increased annually by 1.2% (95% CI; 0.84, 1.50). Incident AF hospitalization was higher among men than women, and 15-fold higher in the 75–84 compared with 35–64 year age group. The age- and sex-standardized prevalence of AF increased annually by 2.0% (95% CI; 1.88, 2.03) over the same period. Comorbidity trends were mixed with diabetes and valvular heart disease increasing, and hypertension, coronary artery disease, heart failure, cerebrovascular disease, and chronic kidney disease decreasing. The 1-year all-cause mortality after incident AF hospitalization declined from 17.6% to 14.6% (trend P < 0.001), with an adjusted hazard ratio of 0.86 (95% CI; 0.81, 0.91). Conclusion This contemporary study shows that incident AF hospitalization is not increasing except for AF as a principal diagnosis, while population prevalence of hospitalized AF has risen substantially. The high 1-year mortality following incident AF hospitalization has improved only modestly over the recent period. [ABSTRACT FROM AUTHOR]

Background Depression in older men has been associated with low circulating testosterone concentration but data from prospective studies are limited. Methods We conducted a prospective longitudinal study in a community representative cohort of 3179 older men free of clinically significant depressive symptoms at baseline. The main objective of this study was to determine if low serum testosterone, dihydrotestosterone and estradiol concentrations are associated with the development of depressive symptoms. Incident depression was assessed with the Patient Health Questionnaire and via an electronic health record database (The West Australian Data Linkage System). The main exposures of interest were serum testosterone, dihydrotestosterone and estradiol measured by liquid chromatography–mass spectrometry and calculated free testosterone in baseline blood samples (collected between 2001 and 2004). Results One hundred and thirty five men (4.2%) developed depression over a median follow up time of 9.4 years (range 8.4–10.9). Men with incident depression were older (median age 77.7 vs 76.1 years, z = −3.82, p = 0 < 0.001) and were more likely to have cardiovascular disease (43.0% vs 32.6%, χ 2 = 6.32, p = 0.012) and diabetes (22.2% vs 13.2%, χ 2 = 8.95, p = 0.003). Low serum total testosterone (<6.4 nmol/L) was associated with incident depression (HR 2.07, 95%CI 1.17–3.68) and this remained significant after adjustment for relevant potential confounding factors (HR 1.86, 95%CI 1.05–3.31). Low serum dihydrotestosterone, estradiol and calculated free testosterone were not associated with risk of depression. Conclusions Low serum total testosterone, but not calculated free testosterone, was associated with incident depression in this sample of older men. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to establish the extent to which frailty was associated with attrition and then compare estimates of frailty prevalence and progression estimated from the observed data to those estimated after imputation. Design Population-based cohort study. Setting The Health in Men Study (HIMS) with frailty estimated at Wave 2 (2001/2004) and Wave 3 (2008) and mortality follow-up to 2010. Participants Participants were 10,305 community-dwelling men aged 70 and older, followed for up to 10 years. Measurements Participants completed an extensive questionnaire covering functional activities and illnesses. Frailty was assessed using the FRAIL Scale and a 32-item Frailty Index. Results Nonresponders at Wave 3 were more likely to have been frail at Wave 2. Imputed estimates of frailty prevalence were 8% to 10% higher than those derived from the observed data. Conclusion Epidemiological surveys may substantially underestimate the levels of frailty among older people in the general population. This selective nonresponse results in an overoptimistic view of aging populations, particularly for the very old. [ABSTRACT FROM AUTHOR]

Background: Improving physical activity levels and diet quality are important for secondary stroke prevention., Aim: To test the feasibility and safety of 6-month, co-designed telehealth-delivered interventions to increase physical activity and improve diet quality., Methods: A 2 × 2 factorial trial (physical activity (PA); diet (DIET); PA + DIET; control) randomized, open-label, blinded endpoint trial. Primary outcomes were feasibility and safety. Secondary outcomes included stroke risk factors (blood pressure, self-report PA (International Physical Activity Questionnaire (IPAQ)) and diet quality (Australian Recommended Food Score (ARFS)), and quality of life. Between-group differences were analyzed using linear-mixed models., Results: Over 23 months, 99 people were screened for participation and 40 (40%) randomized (3 months to 10 years post-stroke, mean age 59 (16) years). Six participants withdrew, and an additional five were lost to follow-up. Fifteen serious adverse events were reported, but none were deemed definitely or probably related to the intervention. Median attendance was 32 (of 36) PA sessions and 9 (of 10) DIET sessions. The proportion of missing primary outcome data (blood pressure) was 3% at 3 months, 11% at 6 months, and 14% at 12 months. Between-group 95% confidence intervals showed promising, clinically relevant differences in support of the interventions across the range of PA, diet quality, and blood pressure outcomes., Conclusion: Our telehealth PA and diet interventions were safe and feasible and may have led to significant behavior change., Trial Registration: ACTRN12620000189921., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Diet quality is a marker of how closely eating patterns reflect dietary guidelines. The highest tertile for diet quality scores is associated with 40% lower odds of first stroke compared with the lowest tertile. Little is known about the diet of stroke survivors. We aimed to assess dietary intake and quality of Australian stroke survivors., Methods: Stroke survivors enrolled in the ENAbLE pilot trial (2019/ETH11533, ACTRN12620000189921) and Food Choices after Stroke study (2020ETH/02264) completed the Australian Eating Survey Food Frequency Questionnaire (AES), a 120-item, semiquantitative questionnaire of habitual food intake over the previous 3-6 months. Diet quality was determined by calculating the Australian Recommended Food Score (ARFS): a higher score indicates higher diet quality., Results: Eighty-nine adult, stroke survivors (female: n = 45, 51%) of mean age 59.5 years (±9.9) had a mean ARFS of 30.5 (±9.9) (low diet quality). Mean energy intake was similar to the Australian population: 34.1% from noncore (energy-dense/nutrient-poor) and 65.9% from core (healthy) foods. However, participants in the lowest tertile for diet quality (n = 31) had significantly lower intake of core (60.0%) and higher intake from noncore foods (40.0%). Most participants did not meet daily requirements for fiber, potassium, or omega 3 fatty acids (2%, 15%, and 18%), nutrients important to reduce stroke risk., Conclusion: The diet quality of stroke survivors was poor, with inadequate intake of nutrients important for reducing recurrent stroke risk. Further research is needed to develop effective interventions to improve diet quality., (© 2023 S. Karger AG, Basel.)

Objective: To determine the prevalence of common mental disorders among older Australians included in the Health In Men Data Linkage Study and compare those with the results of the 2020-2021 National Study of Mental Health and Wellbeing (NSMHW)., Method: We used longitudinal record linkage to estimate the prevalence of mental disorders from age 65 years in a random sample of 38173 Australian men aged 65-85 years living in the Perth metropolitan region. Outcome was the proportion of participants affected by depressive episodes or dysthymia, bipolar disorder, anxiety disorder, psychotic disorder and alcohol use disorder., Results: Prevalence estimates for participants aged 65-69, 70-74, 75-79, 80-84 and ≥85 years were 0.9%, 2.0%, 3.6%, 5.8% and 12.6% for depressive, 0.2%, 0.3%, 0.4%, 0.4% and 0.7% for bipolar, 0.1%, 0.5%, 1.3%, 2.2%, 6.9% for anxiety, 0.2%, 0.4%, 0.5%, 0.4% and 0.6% for psychotic and 1.2%, 1.7%, 2.1%, 2.2% and 4.2% for alcohol use disorders., Conclusions: In contrast to the NSMHW, our data indicate that the prevalence of depressive and anxiety disorders increases with age, particularly among the older old. We conclude that the NSMHW should not be relied upon to guide planning or policies to address the mental health needs of older Australians.

Background: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM 2.5 ), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city., Methods: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996-1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants' residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants., Results: Lung cancer was associated with PM 2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models., Conclusion: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen., (© 2023. The Author(s).)

We investigated the cumulative prevalence of self-harm ideation among stroke survivors of the AFFINITY trial. We assessed these thoughts with the last item of the PHQ-9, and functional impairment with the modified Rankin Scale (mRS). Of 1221 participants (age 63.9 ± 12.3 years, 775 men), 11 reported wishing to die or self-harm at baseline. By week 52, 36 of 1159 surviving participants had reported wishing to die or self-harm. Treatment with fluoxetine for 26 weeks did not change the prevalence of these thoughts compared with placebo. Clinically significant symptoms of depression were present in 95 % of participants with recurrent self-harm thoughts. The study was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000774921., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: Aboriginal Australians are known to suffer high levels of acquired brain injury (stroke and traumatic brain injury) yet experience significant barriers in accessing rehabilitation services. The aim of the Healing Right Way trial is to evaluate a culturally secure intervention for Aboriginal people with newly acquired brain injury to improve their rehabilitation experience and quality of life. Following publication of the trial protocol, this paper outlines the statistical analysis plan prior to locking the database.  METHODS: The trial involves a stepped wedge design with four steps over 3 years. Participants were 108 adult Aboriginal Australians admitted to one of eight hospitals (four rural, four urban) in Western Australia within 6 weeks of onset of a new stroke or traumatic brain injury who consented to follow-up for 26 weeks. All hospital sites started in a control phase, with the intervention assigned to pairs of sites (one metropolitan, one rural) every 26 weeks until all sites received the intervention. The two-component intervention involves training in culturally safe care for hospital sites and enhanced support provided to participants by Aboriginal Brain Injury Coordinators during their hospital stay and after discharge. The primary outcome is quality of life as measured by the Euro QOL-5D-3L VAS. A mixed effects linear regression model will be used to assess the between-group difference at 26 weeks post-injury. The model will control for injury type and severity, age at recruitment and time since commencement of the trial, as fixed effects. Recruitment site and participant will be included as random effects. Secondary outcomes include measurements of function, independence, anxiety and depression, carer strain, allied health occasions of service received and hospital compliance with minimum processes of care based on clinical guidelines and best practice models of care., Discussion: The trial will provide the first data surrounding the effectiveness of an intervention package for Aboriginal people with brain injury and inform future planning of rehabilitation services for this population. The statistical analysis plan outlines the analyses to be undertaken., Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN12618000139279. Registered 30 January, 2018., (© 2022. The Author(s).)

Objectives: The recently developed Hospital Frailty Risk Score (HFRS) allows ascertainment of frailty from administrative data. We aimed to compare the HFRS against the widely used FRAIL Scale and Frailty Index., Design: Population-based cohort study linked to Western Australian Hospital Morbidity Data Collection and Death Registrations., Setting and Participants: The Health in Men Study with frailty determined at Wave 2 (2001/2004), mortality in the 1-year period following Wave 2, and disability at Wave 3 (2008). Participants were 4228 community-based men aged ≥75 years, followed until Wave 3., Measurements: We used multivariable regression to determine the association between each frailty measure and outcomes of length of stay (LOS), death, and disability. We also determined if the additional cases of frailty identified by one measure over the other was associated with these outcomes., Results: Of 4228 men studied, the HFRS (n = 689) identified fewer men as frail than the FRAIL Scale (n = 1648) and Frailty Index (n = 1820). In the fully adjusted models, all 3 frailty measures were associated with longer LOS and mortality, whereas only the FRAIL Scale and Frailty Index were significantly associated with disability. The additional cases of frailty identified by the FRAIL Scale and Frailty Index had longer LOS and greater risks of death and disability. The fully adjusted hazard ratio for death among the additional cases of frailty identified by the FRAIL Scale (compared to being not frail on both HFRS and FRAIL Scale) was 2.14 (95% CI 1.48-3.08)., Conclusions and Implications: The HFRS is associated with adverse outcomes. However, it identified approximately 60% fewer men who were frail than the FRAIL Scale and Frailty Index, and the additional cases identified were also at high risks of adverse outcomes. Users of the HFRS should be aware of the differences with other frailty measures., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate whether diabetes and obesity are associated with frailty independently, and to determine the proportion of frailty cases attributable to each factor., Study Design: Prospective cohort study of 4219 older men assessed in 2001-04 (time-point 1, T1), of whom 1939 were reassessed in 2008-09 (time-point 2, T2). Frailty was defined as positive responses on three or more of the five domains on the FRAIL scale: fatigue, difficulty climbing a flight of stairs (resistance), difficulty walking 100 m (ambulation), >5 illnesses, or >5% weight loss. We explored associations of diabetes and obesity with frailty using binary logistic regression, and estimated population attributable fractions for diabetes and obesity as risk factors for frailty., Main Outcome Measures: Associations of obesity and diabetes with frailty., Results: At T1, 15.5% of participants (n = 652) were frail, 15.4% (n = 651) had diabetes, and 15.1% (n = 636) were obese (BMI ≥ 30 kg/m 2 ). At T2, 22.9% (n = 444) were frail, 19.8% (n = 383) had diabetes and 9.1% (n = 176) were obese. In multivariable models, diabetes was associated with frailty at T1 (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.7-2.6) and T2 (OR = 2.1, CI = 1.6-2.8). Obesity was associated with frailty at T1 (OR = 1.7, CI = 1.3-2.2) only. Both diabetes (OR = 1.5, CI = 1.1-2.2) and obesity (OR = 1.9, CI = 1.3-2.9) at T1 were independently associated with the development of frailty between T1 and T2. Approximately the same proportion (5%) of new frailty cases were attributable to diabetes or to obesity., Conclusions: Diabetes and obesity are modifiable risk factors which independently carry equal risk for the development of frailty in older men. Interventions targeting these risk factors may have the potential to reduce frailty risk., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: To determine the sociodemographic and clinical factors associated with early, late, and persistent clinically significant symptoms of depression during the first year after a stroke., Methods: This cohort study included 1,221 men and women recruited within 2 weeks of stroke onset in Australia, New Zealand, and Vietnam. The NIH Stroke Scale (NIHSS) was used to assess stroke severity. Other study measures included age, sex, marital status, living arrangements, function before the stroke, depression before the stroke, modified Rankin Scale (mRS) score, and treatment with fluoxetine or placebo for 26 weeks. Clinically significant symptoms of depression during the 52 weeks after baseline was the outcome of interest, and the presence of depression was defined by a total Patient Health Questionnaire (PHQ-9) score of ≥9 at week 4, 12, 26, or 52; a clinician diagnosis of depression between assessments; or pharmacologic or psychological treatment of depression during follow-up. Participants were classified as not depressed or as having early (initial 12 weeks), late (12-52 weeks), or persistent (before and after 12 weeks) depression. We used multinomial logistic regression to assess depression risk, with all listed measures entered simultaneously into the model., Results: The mean age of participants was 63.8 (SD 12.3) years, and 775 (63.5%) were male. At baseline, 48 (3.9%) participants had previous treated depression, and 228 (18.7%) had clinically significant symptoms of depression (PHQ-9 score ≥9). Seven hundred thirty-four (63.3%) participants showed no evidence of depression in the year after the stroke; 208 (17.9%) had early, 86 (7.4%) had late, and 131 (11.3%) had persistent depression. Increased stroke severity, as measured by doubling of the NIHSS scores, was associated with an increased risk of early (risk ratio [RR] 2.08, 95% CI 1.65-2.62), late (RR 1.53, 95% CI 1.14-2.06), and persistent (RR = 2.50, 95% CI 1.89-3.32) clinically significant symptoms of depression. Similar findings were apparent for the mRS, a measure of functional disability. Past depression was associated with increased risk of persistent clinically significant symptoms of depression (RR = 6.28, 95% CI 2.88-13.71), as was being married or partnered (RR = 3.94, 95% CI 2.42-6.41). The risk of clinically significant symptoms of depression was higher in Australia and New Zealand than in Vietnam., Discussion: The severity of neurologic and functional deficits increases the risk of poststroke clinically significant symptoms of depression early and persistently. Depression before stroke, personal relationships, and cultural context contribute to mediate depression risk. Interventions that minimize the severity of neurologic and functional deficits should decrease the risk of poststroke clinically significant symptoms of depression., Trial Registration Information: Clinical trial registration number ACTRN12611000774921., (© 2022 American Academy of Neurology.)

Introduction: Despite higher incidence of brain injury among Aboriginal compared with non-Aboriginal Australians, suboptimal engagement exists between rehabilitation services and Aboriginal brain injury survivors. Aboriginal patients often feel culturally insecure in hospital and navigation of services post discharge is complex. Health professionals report feeling ill-equipped working with Aboriginal patients. This study will test the impact of a research-informed culturally secure intervention model for Aboriginal people with brain injury. METHODS AND ANALYSIS: Design: Stepped wedge cluster randomised control trial design; intervention sequentially introduced at four pairs of healthcare sites across Western Australia at 26-week intervals. Recruitment: Aboriginal participants aged ≥18 years within 4 weeks of an acute stroke or traumatic brain injury. Intervention: (1) Cultural security training for hospital staff and (2) local, trial-specific, Aboriginal Brain Injury Coordinators supporting participants. Primary outcome : Quality-of-life using EuroQOL-5D-3L (European Quality of Life scale, five dimensions, three severity levels) Visual Analogue Scale score at 26 weeks post injury. Recruitment of 312 participants is estimated to detect a difference of 15 points with 80% power at the 5% significance level. A linear mixed model will be used to assess the between-condition difference. Secondary outcome measures : Modified Rankin Scale, Functional Independence Measure, Modified Caregiver Strain Index, Hospital Anxiety and Depression Scale at 12 and 26 weeks post injury, rehabilitation occasions of service received, hospital compliance with minimum care processes by 26 weeks post injury, acceptability of Intervention Package, feasibility of Aboriginal Brain Injury Coordinator role. Evaluations : An economic evaluation will determine the potential cost-effectiveness of the intervention. Process evaluation will document fidelity to study processes and capture changing contexts including barriers to intervention implementation and acceptability/feasibility of the intervention through participant questionnaires at 12 and 26 weeks., Ethics and Dissemination: The study has approvals from Aboriginal, university and health services human research ethics committees. Findings will be disseminated through stakeholder reports, participant workshops, peer-reviewed journal articles and conference papers., Trial Registration Number: ACTRN12618000139279., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

While there is clear evidence that high levels of pollution are associated with increased all-cause mortality and cardiovascular mortality and morbidity, the biological mechanisms that would explain this association are less understood. We examined the association between long-term exposure to air pollutants and risk factors associated with cardiovascular disease. Air pollutant concentrations were estimated at place of residence for cohort members in the Western Australian Centre for Health and Ageing Health in Men Study. Blood samples and blood pressure measures were taken for a cohort of 4249 men aged 70 years and above between 2001 and 2004. We examined the association between 1-year average pollutant concentrations with blood pressure, cholesterol, triglycerides, C-reactive protein, and total homocysteine. Linear regression analyses were carried out, with adjustment for confounding, as well as an assessment of potential effect modification. The four pollutants examined were fine particulate matter, black carbon (BC), nitrogen dioxide, and nitrogen oxides. We found that a 2.25 μg/m3 higher exposure to fine particulate matter was associated with a 1.1 percent lower high-density cholesterol (95% confidence interval: -2.4 to 0.1) and 4.0 percent higher serum triglycerides (95% confidence interval: 1.5 to 6.6). Effect modification of these associations by diabetes history was apparent. We found no evidence of an association between any of the remaining risk factors or biomarkers with measures of outdoor air pollution. These findings indicate that long-term PM2.5 exposure is associated with elevated serum triglycerides and decreased HDL cholesterol. This requires further investigation to determine the reasons for this association., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: After an initial stroke, the risk of recurrent stroke is high. Models that implement best-practice recommendations for risk factor management in stroke survivors to prevent stroke recurrence remain elusive. We examined a model which focuses on vascular risk factor management to prevent stroke recurrence in survivors returning to their primary care physicians. This model is coordinated from the stroke unit, integrates specialist stroke services with primary care physicians, and directly involves patients and carers in risk factor management. It is underpinned by the shared care principle in which there is joint participation of specialists as well as primary care physicians in a planned, integrated delivery of care with ongoing involvement of patients and carers, a structure which encourages implementation of best-practice recommendations as well as transferability and sustainability. We hypothesized that an integrated, multimodal intervention based on a shared-care model which supports joint participation of stroke specialists and primary care physicians would improve the implementation of best-practice recommendations for risk factor management in stroke survivors returning to the community., Methods: We undertook a double-blind randomized controlled trial, testing the model in three Australian cities using stroke survivors admitted to stroke units and discharged from hospital to return to their primary care physicians. The model was a shared care, multifaceted integrated program which included bidirectional feedback between general practitioner and specialist unit, education, and engagement of patient and carer in self-management with ongoing input from a multidisciplinary team. The primary endpoint was improvement or abolition of risk factors such as raised blood pressure, diabetes, hyperlipidemia, the modification of adverse life-style factors such as lack of exercise, smoking and alcohol abuse and adherence to preventive medication at one year. Intermediate measurement points were scheduled at three monthly intervals. Analysis was by intention to treat, evaluated by covariance or a linear model adjusting for confounding factors or variance of base-line risk factors. The study was registered as ACTRN = 1261100026498., Results: The study population was as follows: intervention ( n  = 112), control ( n  = 137). At baseline, there was no statistical difference between the groups for any variable. At the 12-month evaluation, there was a significant decrease in systolic blood pressure from baseline in the intervention group of 5.2 mmHg ( p  < 0.01). This change was not observed in the control group ( p  = 0.29). Moreover, at 12 months the mean systolic blood pressure in the intervention group was 129.4 mmHg (SD 14.7), a result which was not obtained in controls. Fasting total cholesterol as well as triglycerides was reduced significantly in the intervention group (both p  < 0.01) but this was not the case in the control group ( p  = 0.11 and p  = 0.27, respectively). At 12 months, there was no change in BMI in the intervention group but there was a significant increase in BMI ( p  = 0.02) in the control group. At 12 months in the intervention group, the mean distance walked with ease compared to the baseline measurements was increased by a mean distance of 600 m while in the control group the distance walked with ease was reduced compared to that measured at baseline. At 12 months, the Barthel index in the intervention group demonstrated improved function ( p  = 0.01), but no change was observed in controls. At 12 months in the intervention group, there was a significant decrease in number of standard alcoholic drinks consumed per week compared to the baseline ( p  = 0.04). This was not observed in the control group ( p  = 0.34)., Conclusion: In stroke survivors, the ICARUSS (Integrated Care for the Reduction of Secondary Stroke) model is superior to usual care with respect to best-practice recommendations for traditional risk factors as well as behavioral and functional outcomes.

Aims: The management of anticoagulation therapy in patients with atrial fibrillation (AF) and cancer is challenging due to increased thrombotic and bleeding risks. We sought to determine the safety and efficacy of rivaroxaban in patients with AF and a history of cancer., Methods and Results: ROCKET AF randomized 14 264 patients with AF to rivaroxaban or warfarin with a median follow-up of 1.9 years. Cox regression models were used to assess the association between cancer history and clinical outcomes, and the relative treatment effect of rivaroxaban vs. warfarin in these patients. A total of 640 patients enrolled in ROCKET AF had a history of cancer, with the most common types being prostate (28.6%), colorectal (16.1%), and breast (14.7%) cancer. Patients with a history of cancer were older, more frequently male, more likely to have prior vitamin K antagonist (VKA) use and had higher rates of overall bleeding [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.16-1.47; P < 0.0001] and non-cardiovascular death (HR 1.47, 95% CI 1.04-2.07; P = 0.031) compared with those with no cancer history. There were no significant associations between cancer history and stroke, venous thromboembolism, or myocardial infarction. The relative efficacy of rivaroxaban vs. warfarin for prevention of stroke/systemic embolism was similar in those with and without a history of cancer (interaction P-value = 0.21)., Conclusion: In ROCKET AF, a history of cancer was associated with a higher risk of bleeding and non-cardiovascular death, but not ischaemic events. The relative efficacy and safety of rivaroxaban compared with warfarin were not significantly different in patients with and without a history of cancer. The results of this study are exploratory and should be taken in context of the study population, which may not be generalizable to those with advanced malignancy. Further investigation is needed to understand optimal anticoagulation strategies in patients with AF and cancer.Clinical trial registration: ClinicalTrials.gov: NCT00403767., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine if hearing loss is associated with increased risk of incident psychosis in later life., Methods: Longitudinal cohort study of a community-representative sample of 38 173 men aged 65 to 85 years at the start of the follow-up period of 18 years. We used the Western Australian Data Linkage System to ascertain the presence of hearing loss and of psychotic disorders according to the International Classification of Diseases (ICD) (versions 8, 9, and 10). We also collected information on concurrent morbidities: cancer and diseases of the cardiovascular, respiratory, digestive, and renal systems., Results: One thousand four hundred forty-two (3.8%) and 464 (1.2%) men had a recorded diagnosis of hearing loss and psychosis at the start of follow-up. After excluding the 464 participants with prevalent psychosis, 37 709 men were available for the longitudinal study, and of these, 252 (0.7%) developed a psychotic disorder. Competing risk regression showed that hearing loss was associated incident psychosis (subhazard ratio = 2.03, 95% CI, 1.24-3.32; after statistical adjustment for age and concurrent morbidities)., Conclusions: Hearing loss is associated with double the risk of incident psychosis in older men. Available evidence suggests that this link could be causal, although conclusive evidence is still missing from randomized controlled trials designed to test the effect of correction of hearing loss on the prevalence and incidence of psychosis., (© 2018 John Wiley & Sons, Ltd.)

Objectives: Older adults living with bipolar disorder (BD) include people with early and late onset of symptoms. This study aimed to clarify the cross-sectional and longitudinal clinical associations of BD with early and late onset., Methods: Cohort study of 38 173 men aged 65-85 years followed for up to 17.6 years. We used the Western Australian Data Linkage System to establish the presence of BD, as well as diabetes, cardiovascular and renal diseases, cancer, respiratory and gastrointestinal diseases, alcohol use disorder, dementia, and mortality. The causes of death were recorded according to the International Classification of Diseases. We defined late onset BD using 2 different cut-points: 50 and 60 years., Results: The prevalence of medical morbidities was greater among participants with than without BD, and cardiovascular diseases were more frequent among those with onset before than after 50 years (odds ratio = 1.72, 95% confidence interval = 1.01, 2.94). Bipolar disorder was associated with increased hazard ratio of dementia and death, but there was no difference between early and late onset participants. Death by suicide or accidents occurred exclusively among BD participants with illness onset <60 years, whereas death associated with strokes and neurodegenerative diseases was more frequent among those with illness onset ≥60 years than in the general population (HR = 2.28, 95% confidence interval = 1.34, 3.88)., Conclusions: Our results indicate that the clinical associations and outcomes of older adults living with BD are not markedly influenced by age of onset. However, mortality data suggest that differences between older adults with BD onset before and after age 60 years should continue to be explored., (© 2018 John Wiley & Sons, Ltd.)

Background: The use of alcohol and drugs is common among people with bipolar disorder, but it is unclear if age of onset modifies this association., Aims: To determine the cross-sectional and longitudinal association between age of onset of bipolar disorder (BD) and disorders associated with the use of alcohol or other substances in later life, as well as their impact on mortality., Methods: Cohort study of a community-representative sample of 38,173 men aged 65-85 years at the start of the follow up period of 18 years. We used the Western Australian Data Linkage System to ascertain the presence of BD and substance use disorders according to the International Classification of Diseases (ICD). We also collected information on concurrent morbidities: diabetes, hypertension, ischaemic heart disease and stroke., Results: 175 men had BD onset < age 60 years and 75 ≥ 60 years. Compared with older men without BD, the adjusted odds of alcohol use disorders were 3.87 (95%CI = 2.52, 5.93) for men with BD onset < 60 years and 2.38 (95%CI = 1.08, 5.25) for those with onset ≥ 60 years. The adjusted hazard ratio of incident disorders associated with the use of alcohol and other substances was 3.23 (95%CI = 1.87, 5.58) and 2.38 (95%CI = 1.38, 4.11) respectively for men with BD onset < 60 years. BD with onset ≥ 60 years was not associated with substance use disorders. The mortality hazard was not affected by the interaction between BD and the use of substances., Conclusions: Substance use disorders (alcohol or others) are more prevalent among older adults with than without BD, but new cases are only more frequent among men with BD onset < 60 years of age. Grouping BD into early and late onset is clinically informative and may affect approach to assessment and management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: A positive association between depression and diabetes has been reported, but the direction and nature of this association is unclear. Insulin resistance is a state of reduced responsiveness of target tissues to normal circulating levels of insulin and predisposes to diabetes in the presence of beta cell dysfunction., Methods: We conducted this cross-sectional and prospective study in a community representative sample of 3,140 older men free of diabetes to determine if insulin resistance was associated with prevalent and incident depressive symptoms., Results: Men with insulin resistance had increased odds of depression cross-sectionally (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.08-2.40), although this was not significant after adjustment for possible confounding (OR: 1.32; 95% CI: 0.85-2.03). In the longitudinal analysis, men with insulin resistance were more likely to develop clinically significant depressive symptoms (adjusted risk ratio [RR]: 2.33; 95% CI: 1.17-4.62), and this risk was greatest for men in the highest quartile of insulin resistance compared with those in the lowest quartile (adjusted RR: 2.54; 95% CI: 1.04-6.18)., Conclusion: Older men with clinically significant depressive symptoms were more likely to have higher markers of insulin resistance. Additionally, the odds of depression increased with increasing levels of insulin resistance, and insulin resistance increased the risk of developing depression over 5 years later. Because depression is now a leading cause of disability worldwide, addressing the rising challenge of insulin resistance may prove important in improving the future health of our communities., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Severe mental illnesses are leading causes of disability worldwide. Their prevalence declines with age, possibly due to premature death. It is unclear, however, if people with severe mental disorders who reach older age still have lower life expectancy compared with their peers and if their causes of death differ., Methods and Findings: Cohort study of a community-representative sample of 37892 Australian men aged 65-85 years in 1996-1998. Follow up was censored on the 31st December 2010. Lifetime prevalence of schizophrenia spectrum, bipolar, depressive and alcohol-induced disorder was established through record linkage. A subsample of 12136 consented to a face-to-face assessment of sociodemographic, lifestyle and clinical variables. Information about causes of death was retrieved from the Australian Death Registry. The prevalence of schizophrenia spectrum, bipolar, depressive and alcohol-induced disorders was 1.2%, 0.3%, 2.5% and 1.8%. The mortality hazard for men with a severe mental disorder was 2.3 and their life expectancy was reduced by 3 years. Mortality rates increased with age, but the gap between men with and without severe mental disorders was not attenuated by age. Cardiovascular diseases and cancer were the most frequent causes of death. The excess mortality associated with severe mental disorders could not be explained by measured sociodemographic, lifestyle or clinical variables., Conclusions: The excess mortality associated with severe mental disorders persists in later life, and the causes of death of younger and older people with severe mental disorders are similar. Hazardous lifestyle choices, suboptimal access to health care, poor compliance with treatments, and greater severity of medical comorbidities may all contribute to this increased mortality. Unlike young adults, most older people will visit their primary care physician at least once a year, offering health professionals an opportunity to intervene in order to minimise the harms associated with severe mental disorders.

Background: There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years., Methods: Method followed was a prospective cohort study of 4,181 men aged 65-84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996-1998 and 2001-2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI., Results: Compared with men with a stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32-2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI >1 kg/m2; this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse "J-shaped" association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable., Conclusions: Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men.

Background: Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial., Methods: 9795 patients aged 50-75 years with type 2 diabetes were followed up for a median of 5 years. Annual rates were derived by the Kaplan-Meier method and independent predictors of risk by Cox proportional hazards regression analyses., Results: The annual rate of stroke was 6.7 per 1000 person years; 82% were ischaemic and caused by small artery disease (36%), large artery disease (17%) and embolism from the heart (13%); 10% were haemorrhagic. Among the strongest baseline predictors of ischaemic or unknown stroke were age (60-65 years, HR 1.98; >65 years, HR 2.35) and a history of stroke or transient ischaemic attack (TIA) (HR 2.06). Other independent baseline predictors were male sex, smoking, history of hypertension, ischaemic heart disease, nephropathy, systolic blood pressure and blood low density lipoprotein (LDL) cholesterol, HbA(1c) and fibrinogen. A history of peripheral vascular disease, low high density lipoprotein, age and history of hypertension were associated with large artery ischaemic stroke. A history of diabetic retinopathy, LDL cholesterol, male sex, systolic blood pressure, smoking, diabetes duration and a history of stroke or TIA were associated with small artery ischaemic stroke., Conclusions: Older people with a history of stroke were at highest risk of stroke, but the prognosis and prognostic factors of subtypes were heterogeneous. The results will help clinicians quantify the absolute risk of stroke and its subtypes for typical diabetes patients.

Background: Estimates of the absolute risk of death based on the combined effects of sex, age and health behaviours are scarce for elderly people. The aim of this paper is to calculate population based estimates and display them using simple charts that may be useful communication tools for public health authorities, health care providers and policy makers., Methods: Data were drawn from two concurrent prospective observational cohort studies of community-based older Australian women (N = 7,438) and men (N = 6,053) aged 71 to 79. The outcome measure was death within ten years. The predictor variables were: sex, age, smoking status, alcohol consumption, body mass index and physical activity., Results: Patterns of risks were similar in men and women but absolute risk of death was between 9 percentage points higher in men (17 %) than in women (8 %) in the lowest risk group (aged 71-73 years, never smoked, overweight, physically active and consumed alcohol weekly) and 21 % higher in men (73-74 %) than women (51-52 %) in the highest risk group (aged 77-79 years, normal weight or obese, current smoker, physically inactive and drink alcohol less than weekly)., Conclusions: These absolute risk charts provide a tool for understanding the combined effects of behavioural risk factors for death among older people.

Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer., Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010., Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00-1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21-1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53-5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers., Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer., Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy., (©2012 AACR.)

Background: Regular physical activity is associated with reduced risk of mortality in middle-aged adults; however, associations between physical activity and mortality in older people have been less well studied. The objective of this study was to compare relationships between physical activity and mortality in older women and men., Methods: The prospective cohort design involved 7080 women aged 70-75 years and 11 668 men aged 65-83 years at baseline, from two Australian cohorts - the Australian Longitudinal Study on Women's Health and the Health in Men Study. Self-reported low, moderate and vigorous intensity physical activity, socio-demographic, behavioural and health characteristics were assessed in relation to all-cause mortality from the National Death Index from 1996 to 2009; the median follow-up of 10.4 (women) and 11.5 (men) years., Results: There were 1807 (25.5%) and 4705 (40.3%) deaths in women and men, respectively. After adjustment for behavioural risk factors, demographic variables and self-reported health at baseline, there was an inverse dose - response relationship between physical activity and all-cause mortality. Compared with women and men who reported no activity, there were statistically significant lower hazard ratios for women who reported any activity and for men who reported activities equivalent to at least 300 metabolic equivalent.min/week. Risk reductions were 30-50% greater in women than in men in every physical activity category., Conclusions: Physical activity is inversely associated with all-cause mortality in older men and women. The relationship is stronger in women than in men, and there are benefits from even low levels of activity.

Background: Frailty is a syndrome characterized by diminished ability to re-establish homeostasis in response to stress. We hypothesized that deficient allostatic responses to physiological challenges may predispose to frailty, that C-reactive protein (CRP) and its genetic determinants may be a measure of the integrity of the allostatic response, and that genetic determinants of the allostatic response determine the risk of frailty., Methods: Cross-sectional study of 3778 community-dwelling older men identified by random sampling of the Australian electoral roll. Explanatory variables included demographic, clinical, lifestyle behaviors, serum high-sensitivity CRP (hsCRP), and CRP 1444C>T and 1846G>A genotypes. These respective polymorphisms increase and decrease the basal concentration of hsCRP. The study outcome was frailty defined by a score of ≥4 on the FRAIL scale., Results: The mean age of participants was 77.1 years (SD: 3.6) and frailty was present in 196 (5.2%). The serum concentration of hsCRP was higher in frail than non-frail men (p<0.001), but levels varied according to genotypes. The odds of frailty increased progressively from GG to GA and AA genotypes of the CRP1846G>A gene (z=3.93, p<0.001), and were 2.43 (95%CI=1.62-3.67) times greater in men with CRP1846G>A AA compared with GG genotypes. The CRP 1444C>T was not associated with frailty., Conclusion: Frail people have raised serum concentrations of CRP, presumably in response to the stress of underlying cause(s). However, frail individuals carrying the CRP1846G>A polymorphism seem less able to mount an efficient allostatic response, which may underpin their increased odds of frailty., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine if older men who use computers have lower risk of developing dementia., Methods: Cohort study of 5506 community-dwelling men aged 69 to 87 years followed for up to 8.5 years. Use of computers measured as daily, weekly, less than weekly and never. Participants also reported their use of email, internet, word processors, games or other computer activities. The primary outcome was the incidence of ICD-10 diagnosis of dementia as recorded by the Western Australian Data Linkage System., Results: 1857/5506 (33.7%) men reported using computers and 347 (6.3%) received a diagnosis of dementia during an average follow up of 6.0 years (range: 6 months to 8.5 years). The hazard ratio (HR) of dementia was lower among computer users than non-users (HR = 0.62, 95%CI = 0.47-0.81, after adjustment for age, educational attainment, size of social network, and presence of depression or of significant clinical morbidity). The HR of dementia appeared to decrease with increasing frequency of computer use: 0.68 (95%CI = 0.41-1.13), 0.61 (95%CI = 0.39-0.94) and 0.59 (95%CI = 0.40-0.87) for less than weekly, at least weekly and daily. The HR of dementia was 0.66 (95%CI = 0.50-0.86) after the analysis was further adjusted for baseline cognitive function, as measured by the Mini-Mental State Examination., Conclusion: Older men who use computers have lower risk of receiving a diagnosis of dementia up to 8.5 years later. Randomised trials are required to determine if the observed associations are causal.

Aim: To review findings from the Men, Women and Ageing (MWA) longitudinal studies and consider their implications for national health guidelines., Methods: Guidelines for good health for older adults in the areas of body mass index (BMI), physical activity, alcohol consumption and smoking behaviours are compared with MWA findings., Results: Findings from MWA suggest that current BMI guidelines may be too narrow because BMI in the overweight range appears to be protective for both older men and women. Across all levels of BMI, even low levels of physical activity decrease mortality risk compared with being sedentary. Our findings suggest that consideration should be given to having different alcohol guidelines for older men and women and should include recommendations for alcohol-free days. The benefit of quitting smoking at any age is apparent for both women and men., Conclusions: Current national guidelines in the areas discussed in this paper should be reviewed for older people., (© 2011 The Authors. Australasian Journal on Ageing © 2011 ACOTA.)

Background: Vision and hearing decline with age. Loss of these senses is associated with increased risk of falls, injuries from falls, mortality and decreased health-related quality of life (HRQOL). Our objective was to determine if there are gender differences in the associations between visual and hearing impairment and these outcomes., Methods: 2340 men and 3014 women aged 76-81 years from the Health in Men Study and the Australian Longitudinal Study on Women's Health were followed for an average of 6.36 years. Dependent variables were self-reported vision and hearing impairment. Outcome variables were falls, injuries from falls, physical and mental components of HRQOL (SF-36 PCS and MCS) and all-cause mortality., Results: Vision impairment was more common in women and hearing impairment was more common in men. Vision impairment was associated with increased falls risk (odds ratio (OR)=1.77, 95% CI=1.35-2.32 in men; OR=1.82, 95% CI=1.44-2.30 in women), injuries from falls (OR=1.69, 95% CI=1.23-2.34 in men, OR=1.79, 95% CI=1.38-2.33 in women), and mortality (hazard ratio (HR)=1.44; 95% CI=1.17-1.77 in men; HR=1.50, 95% CI=1.24-1.82 in women) and declines in SF-36 PCS and MCS. Hearing impairment was associated with increased falls risk (OR=1.38, 95% CI=1.08-1.78 in men; OR=1.45, 95% CI=1.08-1.93 in women) and declines in SF-36 PCS and MCS. Overall there were no gender differences in the association between vision and hearing impairment and the outcomes., Conclusion: In men and women aged 76-81 years, there were no gender differences in the association between self-reported vision and hearing impairment and the outcomes of falls, mortality and HRQOL., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Circulating IGF1 declines with age while ill-health increases. Controversy remains whether differences in the levels of IGF1 and its binding proteins 1 and 3 (IGFBP1 and IGFBP3) determine health outcomes during ageing. We examined associations of IGF1, IGFBP1 and IGFBP3 with all-cause and cardiovascular mortality in older men., Design: We conducted a prospective cohort study of community-dwelling men aged ≥70 years., Methods: Plasma collected at baseline (2001-2004) was assayed for total IGF1, IGFBP1 and IGFBP3. Incidence and causes of death from time of recruitment to 31 December 2008 were ascertained using the Western Australian Data Linkage System. Cox regression analyses were performed, adjusting for conventional cardiovascular risk factors., Results: Among 3983 men followed for 5.2 years (median), 694 deaths occurred, 243 from cardiovascular disease (CVD). There was no difference in survival according to quintiles of IGF1. Increased IGFBP1 predicted increased all-cause mortality (highest versus lowest quintile: adjusted hazard ratio (HR)=1.98, 95% confidence interval (CI)=1.52-2.57, P<0.001 for trend) and increased cardiovascular mortality (HR=3.42 (2.03-5.77), P<0.001 for trend). Decreased IGFBP3 predicted increased all-cause mortality (lowest versus highest quintile: HR=1.57, 95% CI=1.23-2.01, P=0.007 for trend). Associations of IGFBP1 and IGFBP3 with all-cause mortality were not attenuated by adjustment for IGF1 levels., Conclusions: In older men, higher IGFBP1 and lower IGFBP3 levels predict overall and CVD-related mortality, while IGF1 levels are not associated with mortality. Further studies are needed to clarify the underlying mechanisms by which IGFBP1 and IGFBP3 levels are associated with mortality risk, and whether this occurs independently of IGF1.

Objective: To determine if adiposity in later life increases dementia hazard., Methods: Cohort study of 12,047 men aged 65-84 years living in Perth, Australia. Adiposity exposures were baseline body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). We used the Western Australian Data Linkage System (WADLS) to establish the presence of new cases of dementia between 1996 and 2009 according to the International Classification of Diseases (ICD). Crude and adjusted hazard ratio (HR, 95% confidence interval, 95%CI) of dementia for each adiposity marker was calculated using Cox regression models. Other measured factors included age, marital status, education, alcohol use, smoking, diet, physical activity, and prevalent hypertension, diabetes, dyslipidaemia and cardiovascular disease., Results: Compared with men with BMI<25, participants with BMI between 25-30 had lower adjusted HR of dementia (HR = 0.82, 95% CI = 0.70-0.95). The HR of dementia for men with BMI ≥ 30 was comparable to men with BMI<25 (HR = 0.82, 95%CI = 0.67-1.01). Waist circumference showed no obvious association with dementia hazard. Men with WHR ≥ 0.9 had lower adjusted HR of dementia than men with WHR <0.9 (HR = 0.82, 95%CI  =  0.69-0.98). We found a "J" shape association between measures of obesity and the hazard of dementia, with the nadir of risk being in the overweight range of BMI and about 1 for WHR., Conclusions: Higher adiposity is not associated with incident dementia in this Australian cohort of older men. Overweight men and those with WHR ≥ 0.9 have lower hazard of dementia than men with normal weight and with WHR<0.9.