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ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).MethodsBlinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.ConclusionsNon-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Obstructive sleep apnea (OSA) may increase stroke risk; retinal arteriolar (central retinal arteriolar equivalent, CRAE) diameter narrowing and/or retinal venular (central retinal venule equivalent, CRVE) widening may predict stroke. We examined relationships between sleep disordered breathing (SDB) and CRAE and CRVE and in a diabetes-free sleep clinic cohort. Patients for SDB assessment were recruited (Main Group, n = 264, age: 58.5 ± 8.9 yrs [mean ± SD]; males: 141) for in-laboratory polysomnography (standard metrics, eg apnea hypopnea index, AHI) and retinal photographs (evening and morning). A more severe SDB sub-group (n = 85) entered a 12-month cardiovascular risk factor minimisation (hypertension/hypercholesterolemia control; RFM) and continuous positive airway pressure (CPAP) intervention (RFM/CPAP Sub-Group); successfully completed by n = 66 (AHI = 32.4 [22.1-45.3] events/hour, median[IQR]). Univariate (Spearman's correlation, t-test) and multiple linear regression models examined non-SDB and SDB associations with CRAE and CRVE measures. Main Group: Evening CRAE predictors were: systolic blood pressure (0.18μm decrease per mmHg, p = 0.001), age (2.47μm decrease per decade, p = 0.012), Caucasian ethnicity (4.45 μm versus non-Caucasian, p = 0.011), height (0.24 μm decrease per cm increase, p = 0.005) and smoking history (3.08 μm increase, p = 0.052). Evening CRVE predictors were: Caucasian ethnicity (11.52 μm decrease versus non-Caucasian, p>0.001), diastolic blood pressure (0.34 μm increase in CRVE per mmHg, p = 0.001), hypertension history (6.5 μm decrease, p = 0.005), and smoking history (4.6 μm increase, p = 0.034). No SDB metric (all p>0.08) predicted CRAE or CRVE measures. RFM/CPAP Sub-Group: A one-unit increase in ln(AHI+1) was associated with a 0.046μm increase in CRAE (n = 85; p = 0.029). Mean evening CRAE and CRVE values did not change across the intervention (n = 66), but evening CRVE decreased ~6.0 μm for individuals with AHI >30 events/hr. No major SDB associations with CRAE or CRVE were identified, although the RFM/CPAP intervention reduced evening CRVE for severe OSA patients. Implications for cerebro-vascular disease risk remain uncertain. The protocol was registered with the Australian New Zealand Clinical Trials Registry (Trial Id: ACTRN12620000694910).

Objectives To examine baseline frailty and its association with rehospitalisation and mortality within 12 months among older adults enrolled in the Western Sydney Clinical Frailty Registry. Design Prospective observational cohort study. Setting and participants 592 adults admitted to an acute geriatric medicine service in NSW, Australia, were included in this study. Methods The Western Sydney Clinical Frailty Registry is a study of adults admitted to acute geriatric wards in a 570-bed two-site district general hospital in Western Sydney, NSW, Australia. Recruitment began in April 2020 and is ongoing. Each participant is recruited while an inpatient and followed up for 12 months, including baseline visits and three-, six- and 12-month follow-ups via telephone interviews. The primary outcome of this study was rehospitalisation and/or mortality at 12 months. Results Median age 82 years; half the cohort were classified as mild-moderately frail, and 21% were classified as severely frail. A total of 134 participants died (22.6%) within the 12-month follow-up period. Increased cumulative incidence of first rehospitalisation and/or death during the first 12 months post-discharge was significantly associated with higher modified Charlson comorbidity (p < 0.001) and Clinical Frailty Scale (CFS) scores (p < 0.001). Compared to the ‘non-frail’ group (CFS 1–4), those who were severely frail (CFS 7–9) had an 85% increased risk of rehospitalisation and/or death (95% CI 1.36–2.52), and those who were mild-moderately frail (CFS 5–6) had a 52% increased risk after adjusting for effects of the other variables (95% CI 1.18–1.94). Conclusions Frailty is very common in older adults admitted to acute geriatric services. Assessing frailty using the CFS is feasible and is independently predictive of rehospitalisation and mortality. Our findings suggest that integrating frailty assessment into clinical practice goes beyond simple risk stratification, offering valuable insights for tailored clinical management strategies.

Digitally enabled rehabilitation may lead to better outcomes but has not been tested in large pragmatic trials. We aimed to evaluate a tailored prescription of affordable digital devices in addition to usual care for people with mobility limitations admitted to aged care and neurological rehabilitation. We conducted a pragmatic, outcome-assessor-blinded, parallel-group randomised trial in 3 Australian hospitals in Sydney and Adelaide recruiting adults 18 to 101 years old with mobility limitations undertaking aged care and neurological inpatient rehabilitation. Both the intervention and control groups received usual multidisciplinary inpatient and post-hospital rehabilitation care as determined by the treating rehabilitation clinicians. In addition to usual care, the intervention group used devices to target mobility and physical activity problems, individually prescribed by a physiotherapist according to an intervention protocol, including virtual reality video games, activity monitors, and handheld computer devices for 6 months in hospital and at home. Co-primary outcomes were mobility (performance-based Short Physical Performance Battery [SPPB]; continuous version; range 0 to 3; higher score indicates better mobility) and upright time as a proxy measure of physical activity (proportion of the day upright measured with activPAL) at 6 months. The dataset was analysed using intention-to-treat principles. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000936628). Between 22 September 2014 and 10 November 2016, 300 patients (mean age 74 years, SD 14; 50% female; 54% neurological condition causing activity limitation) were randomly assigned to intervention (n = 149) or control (n = 151) using a secure online database (REDCap) to achieve allocation concealment. Six-month assessments were completed by 258 participants (129 intervention, 129 control). Intervention participants received on average 12 (SD 11) supervised inpatient sessions using 4 (SD 1) different devices and 15 (SD 5) physiotherapy contacts supporting device use after hospital discharge. Changes in mobility scores were higher in the intervention group compared to the control group from baseline (SPPB [continuous, 0-3] mean [SD]: intervention group, 1.5 [0.7]; control group, 1.5 [0.8]) to 6 months (SPPB [continuous, 0-3] mean [SD]: intervention group, 2.3 [0.6]; control group, 2.1 [0.8]; mean between-group difference 0.2 points, 95% CI 0.1 to 0.3; p = 0.006). However, there was no evidence of a difference between groups for upright time at 6 months (mean [SD] proportion of the day spent upright at 6 months: intervention group, 18.2 [9.8]; control group, 18.4 [10.2]; mean between-group difference -0.2, 95% CI -2.7 to 2.3; p = 0.87). Scores were higher in the intervention group compared to the control group across most secondary mobility outcomes, but there was no evidence of a difference between groups for most other secondary outcomes including self-reported balance confidence and quality of life. No adverse events were reported in the intervention group. Thirteen participants died while in the trial (intervention group: 9; control group: 4) due to unrelated causes, and there was no evidence of a difference between groups in fall rates (unadjusted incidence rate ratio 1.19, 95% CI 0.78 to 1.83; p = 0.43). Study limitations include 15%-19% loss to follow-up at 6 months on the co-primary outcomes, as anticipated; the number of secondary outcome measures in our trial, which may increase the risk of a type I error; and potential low statistical power to demonstrate significant between-group differences on important secondary patient-reported outcomes. In this study, we observed improved mobility in people with a wide range of health conditions making use of digitally enabled rehabilitation, whereas time spent upright was not impacted. The trial was prospectively registered with the Australian New Zealand Clinical Trials Register; ACTRN12614000936628.

ObjectiveWe performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).MethodsWe searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3–6 or 2–6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.ResultsWe included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).ConclusionsFLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.PROSPERO registration numberCRD42019131168.

Stroke causes around 730,000 deaths in South Asia, nearly half of stroke-related deaths in developing countries. This highlights the need to address health system responses, considering poverty, service quality, and availability. The article identifies four key challenges in stroke management and rehabilitation in South Asia, emphasizing long-term monitoring, risk factor control, and community surveillance, drawing on experiences from Nepal.

ObjectiveTo examine the feasibility of implementing remote atrial fibrillation (AF) self-screening among older people supported by a remote central monitoring system.DesignProcess evaluation of the Mass AF randomised clinical trial (ACTRN12621000184875) with one-to-one semistructured interviews using interview guides underpinned by the Critical Realism approach and coded using the UK Medical Research Council Guidance of Process Evaluation Framework.Setting and participantsCommunity-dwelling people aged ≥75 years from both genders (ratio 1:1) and urban/rural (ratio 2:1) in Australia.InterventionsParticipants were provided handheld single-lead electrocardiogram (ECG) devices and trained to self-record ECGs once daily on weekdays for at least 6 months. A remote central team notified participants and general practitioners (GPs) of AF.Primary feasibility outcomesThe strengths, weaknesses, opportunities and threats (SWOT) analysis examined enablers (ie, strengths and opportunities) and barriers (ie, weaknesses and threats).ResultsOverall, 200 participants; 98.5% completed the 6-month programme, 96% reported being satisfied with screening and 48 were interviewed: mean age 79 years, 54% male and 71% urban. 11 GPs were interviewed: 55% female and 64% urban. Programme participants trusted the remote monitoring system that supported the screening programme and provided follow-up pathways where required. GPs saw opportunities to introduce this self-screening programme to at-risk patients and improve patients’ risk profiles. Programme participants reported that after being trained to use the device, they felt empowered to do self-screening and found it convenient. GPs saw empowerment could enhance the doctor–patient relationship. Programme participants and GPs valued screening in diagnosing AF that would otherwise be missed in usual care, but the uncertainty of effective screening duration could be a barrier.ConclusionsThis screening programme was feasible with the reinforcement of the underpinning enablers. Several implementation strategies were identified using SWOT analysis, including leveraging the opportunity for GPs to introduce this screening programme to at-risk patients.Trial registration numberACTRN12621000184875.

Elderly people do not mount strong immune responses to vaccines. We compared 23-valent capsular polysaccharide (23vPPV) alone versus 7-valent conjugate (PCV7) vaccine followed by 23vPPV 6 months later in hospitalized elderly. Participants were randomized to receive 23vPPV or PCV7-23vPPV. Antibodies against serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F, 23F were measured by enzyme-linked immunosorbent (ELISA) and opsonophagocytic (OPA) assays at baseline, 6 months and 12 months. Of 312 recruited, between 40% and 72% of subjects had undetectable OPA titres at baseline. After one dose, PCV7 recipients had significantly higher responses to serotypes 9V (both assays) and 23F (OPA only), and 23vPPV recipients had significantly higher responses to serotype 3 (ELISA), 19F and 19A (OPA only). In subjects with undetectable OPA titres at baseline, a proportionately greater rise in OPA titre (P<0.01) was seen for all serotypes after both vaccines. The GMT ratio of OPA was significantly higher at 12 months in the PCV7-23vPPV group for serotypes 6A, 9V, 18C and 23F. OPA titre levels for these serotypes increased moderately after 6 months, whereas immunity waned in the 23vPPV only arm. We did not show overwhelming benefit of one vaccine over the other. Low baseline immunity does not preclude a robust immune response, reiterating the importance of vaccinating the frail elderly. A schedule of PCV7-23vPPV prevents waning of antibody, suggesting that both vaccines could be useful in the elderly. Follow up studies are needed to determine persistence of immunity. The Australian Clinical Trials Registry ACTRN12607000387426.

The effect of alteplase on patient survival after ischaemic stroke is the subject of debate. We report the effect of intravenous alteplase on long-term survival after ischaemic stroke of participants in the Third International Stroke Trial (IST-3). In IST-3, done at 156 hospitals in 12 countries (Australia, Europe, and the UK), participants (aged >18 years) were randomly assigned with a telephone voice-activated or web-based system in a 1:1 ratio to treatment with intravenous 0·9 mg/kg alteplase plus standard care or standard care alone within 6 h of ischaemic stroke. We followed up participants in the UK and Scandinavia (Sweden and Norway) for survival up to 3 years after randomisation using data from national registries and compared survival in the two groups with proportional hazards survival analysis, adjusting for key prognostic variables. IST-3 is registered with the ISRCTN registry, number ISRCTN25765518. Between May 5, 2000, and July 27, 2011, 3035 participants were enrolled in IST-3. Of these, 1948 (64%) of 3035 participants were scheduled for analysis of 3 year survival, and 1946 (>99%) of these were included in the analysis (967 [50%] in the alteplase plus standard care group and 979 [50%] in the standard care alone group). By 3 years after randomisation, 453 (47%) of 967 participants in the alteplase plus standard care group and 494 (50%) of 979 in the standard care alone group had died (risk difference 3·6% [95% CI −0·8 to 8·1]). Participants allocated to alteplase had a significantly higher hazard of death during the first 7 days (99 [10%] of 967 died in the alteplase plus standard care group vs 65 [7%] of 979 in the standard care alone group; hazard ratio 1·52 [95% CI 1·11–2·08]; p=0·004) and a significantly lower hazard of death between 8 days and 3 years (354 [41%] of 868 vs 429 [47%] of 914; 0·78 [0·68–0·90]; p=0·007). Alteplase treatment within 6 h after ischaemic stroke was associated with a small, non-significant reduction in risk of death at 3 years, but among individuals who survived the acute phase, treatment was associated with a significant increase in long-term survival. These results are reassuring for clinicians who have expressed concerns about the effect of alteplase on survival. Heart and Stroke Scotland, UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, AFA Insurance, Swedish Heart Lung Fund, Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, Australian Heart Foundation, Australian National Health and Medical Research Council, Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita (Regione dell'Umbria), and Danube University.

Background The health issues experienced by older people can often be severe and complex, and an increasing number are using residential aged care services to meet their care needs. High-quality nursing care is fundamental to the health and safety of aged care residents and is contingent on nurses’ accurate assessment, informed decision-making, and delivery of timely interventions. However, the role of the aged care nurse is often challenging, impeded by factors such as understaffing, high workloads, and a lack of access to clinical infrastructure and resources. When these challenges mount, residents are put at greater risk of adverse outcomes, such as avoidable clinical deterioration and hospital transfers. This study describes the adaptation and implementation of the emergency nursing framework, HIRAID® (History including Infection risk, Red Flags, Assessment, Interventions, Diagnostics, reassessment, communication and plan)—a tool to assist nurses’ assessment, decision-making and care in residential aged care. Methods The HIRAID® framework will be adapted for residential aged care using a real-time Delphi and panel of aged care and nursing experts. The co-designed HIRAID® Aged Care framework will be trialled in 23 residential aged care homes in Sydney, Australia, in a modified stepped-wedge cluster randomised controlled trial design. All homes will be randomised into one of four clusters. Outcomes of interest include the rate of clinical deterioration events resulting from nurses’ actions, the rate of hospital transfers determined to be inappropriate, performance against the national mandatory aged care quality indicators, resident satisfaction with care, nurse and medical staff satisfaction with communication, and the quality of nursing documentation. These outcomes will be evaluated using a combination of qualitative and quantitative analysis of routinely collected resident data, expert assessments of facility documentation events against validated criteria, and pre- and post-intervention surveys of residents, family carers, nurses, and medical staff. Discussion This protocol describes a pragmatic trial that aims to translate an evidence-based framework from the emergency care context into residential aged care. The adapted HIRAID® Aged Care framework will be the first of its kind to standardise and guide holistic nursing assessment, decision-making, and documentation in residential aged care in Australia. Ethics and dissemination This research has been approved by the Western Sydney Local Health District Human Research Ethics Committee: 2023/ETH00523. A waiver of consent has been approved to access resident health data and nursing documentation at each participating site. Trial registration Australian and New Zealand Clinical Trial Registry, ACTRN12623000481673. Registered 12 May 2023. Protocol version Version 1.0 6 February 2024.