Search

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., (© 2024. The Author(s).)

Objective: To examine the feasibility of implementing remote atrial fibrillation (AF) self-screening among older people supported by a remote central monitoring system., Design: Process 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 Participants: Community-dwelling people aged ≥75 years from both genders (ratio 1:1) and urban/rural (ratio 2:1) in Australia., Interventions: Participants 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 Outcomes: The strengths, weaknesses, opportunities and threats (SWOT) analysis examined enablers (ie, strengths and opportunities) and barriers (ie, weaknesses and threats)., Results: Overall, 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. 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., Conclusions: This 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 Number: ACTRN12621000184875., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Diagnosis of atrial fibrillation (AF) provides opportunities to reduce stroke risk. This study aimed to compare AF diagnosis rates, participant satisfaction and feasibility of an electrocardiogram (ECG) self-screening virtual care system with usual care., Methods: This randomised controlled implementation study involving community-dwelling people aged ≥75 years was conducted from May 2021 to June 2023. Participants were given a handheld single-lead ECG device and trained to self-record ECGs once daily on weekdays for 12 months. The control group received usual care with their general practitioners in the first 6 months and participated in the subsequent 6 months. AF diagnosis and participant satisfaction were assessed at 6 months., Results: 200 participants (mean age 79.0±3.4 years; 54.0% female; 72.5% urban). AF was diagnosed in 10/97 (10.3%) intervention participants and 2/100 (2.0%) in the control group (Odds Ratio 5.6, 95% CI 1.4-37.3, p=0.03). In the intervention, 80% of AF cases were diagnosed within 3 months. 91/93 (97.9%) intervention participants and 55/93 (59.1%) control-waitlisted participants (p<0.001) were satisfied with AF screening. Of the expected 20 days per month, the overall monthly median number of days participants self-recorded ECGs was 20 (interquartile range 17-22). Participants were confident using the device (93%), reported it was easy to use (98%) and found screening efficient (96%)., Conclusions: Patient-led AF self-screening using single-lead ECG devices with a remote central monitoring system was feasible, acceptable, and effective in diagnosing AF among older people. This screening model could be adapted for implementation, interfacing with integrated care models within existing health systems., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study)., Methods and Results: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P <0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age., Conclusions: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score., Registration: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

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., Competing Interests: Shiva Raj Mishra serves as a deputy editor in Global Heart. The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Introduction: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)., Methods: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death)., Results: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p &lt; 0.001)., Conclusion: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days., (© 2024 S. Karger AG, Basel.)

Background and Objectives: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD., Methods: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies. Outcomes were SBI (primary) and individual CSVD subtypes. Summary prevalence (95% confidence intervals [CIs]) were obtained using random-effects meta-analysis. Pooled prevalence ratios (PRs) (95% CI) were calculated to compare those with heart disease with available control participants without heart disease from studies., Results: A total of 221 observational studies were included. In those with AF, the prevalence was 36% (31%-41%) for SBI (70 studies, N = 13,589), 25% (19%-31%) for lacune (26 studies, N = 7,172), 62% (49%-74%) for white matter hyperintensity/hypoattenuation (WMH) (34 studies, N = 7,229), and 27% (24%-30%) for microbleed (44 studies, N = 13,654). Stratification by studies where participants with recent stroke were recruited identified no differences in the prevalence of SBI across subgroups ( p homogeneity = 0.495). Results were comparable across participants with different heart diseases except for those with PFO, in whom there was a lower prevalence of SBI [21% (13%-30%), 11 studies, N = 1,053] and CSVD. Meta-regressions after pooling those with any heart disease identified associations of increased (study level) age and hypertensives with more SBIs and WMH ( p regression <0.05). There was no evidence of a difference in the prevalence of microbleed between those with and without heart disease (PR [95% CI] 1.1 [0.7-1.7]), but a difference was seen in the prevalence of SBI and WMH (PR [95% CI] 2.3 [1.6-3.1] and 1.7 [1.1-2.6], respectively)., Discussion: People with heart disease have a high prevalence of SBI (and CSVD), which is similar in those with vs without recent stroke. More research is required to assess causal links and implications for management., Trial Registration Information: PROSPERO CRD42022378272 (crd.york.ac.uk/PROSPERO/).

With population ageing, drug trials are increasingly turning their attention to including older, frailer people. This review aimed to provide an overview of how frailty was assessed in published studies related to clinical pharmacological trials, and on the interaction of frailty on the efficacy of the treatments. We searched MEDLINE, EMBASE and Cochrane for clinical drug trials in older people. A total of 4031 abstracts were screened and 17 relevant studies were included in this review. We summarized the findings of these 17 trials into five main clinical areas: cardiovascular (eight studies), cognition (one study), vaccination (two studies), cancer (four studies) and other (two studies). Frailty was assessed retrospectively in most of the studies. Frailty was treated as an ordinal variable (with different levels of frailty) or binary variable (frail/non-frail) using cut-offs in some studies, and as a continuous in some other studies. The effect of frailty on the treatment efficacy was not consistent among the studies. While several trials, such as the Action in Diabetes and Vascular Disease-Preterax and Diamicron Modified Release Controlled Evaluation trials, the Systolic Blood Pressure Intervention Trial and the Aspirin in Reducing Events in the Elderly trial, showed some reduced effects of the treatment in frail patients, most of the trials showed that the benefits of the treatment are not affected by frailty. Some trials even showed that the benefits of the treatment were more significant in frailer patients (the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure and the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure trials). The results of this review suggest that routine measurement of frailty in participants in clinical drug trials would improve our knowledge of the effect of treatment in the frail and identify those who have more or least to gain from treatment., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objectives: To evaluate the effect of a coaching intervention compared with control on physical activity and falls rate at 12 months in community-dwelling people aged 60+ years., Design: Cluster randomised controlled trial., Setting: Community-dwelling older people., Participants: 72 clusters (605 participants): 37 clusters (290 participants) randomised to the intervention and 35 (315 participants) to control., Intervention: Intervention group received written information, fall risk assessment and prevention advice by a physiotherapist, activity tracker and telephone-based coaching from a physiotherapist focused on safe physical activity. Control group received written information and telephone-based dietary coaching. Both groups received up to 19 sessions of telephone coaching over 12 months., Outcomes: The co-primary outcomes were device-measured physical activity expressed in counts per minute at 12 months and falls rate over 12 months. Secondary outcomes included the proportion of fallers, device-measured daily steps and moderate-to-vigorous physical activity (MVPA), self-reported hours per week of physical activity, body mass index, eating habits, goal attainment, mobility-related confidence, quality of life, fear of falling, risk-taking behaviour, mood, well-being and disability., Results: The mean age of participants was 74 (SD 8) years, and 70% (n=425) were women. There was no significant effect of the intervention on device-measured physical activity counts per minute (mean difference 5 counts/min/day, 95% CI -21 to 31), or falls at 12 months (0.71 falls/person/year in intervention group and 0.87 falls/person/year in control group; incidence rate ratio 0.86, 95% CI 0.65 to 1.14). The intervention had a positive significant effect on device-measured daily steps and MVPA, and self-reported hours per week of walking, well-being, quality of life, and disability. No significant between-group differences were identified in other secondary outcomes., Conclusion: A physical activity and fall prevention programme including fall risk assessment and prevention advice, plus telephone-based health coaching, did not lead to significant differences in physical activity counts per minute or falls rate at 12 months. However, this programme improved other physical activity measures (ie, daily steps, MVPA, hours per week of walking), overall well-being, quality of life and disability., Trial Registration Number: ACTRN12615001190594., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The ongoing OPTIMISTmain study, an international, multicenter, stepped-wedge cluster randomized trial, aims to determine effectiveness and safety of low-intensity versus standard monitoring in thrombolysis-treated patients with mild-to-moderate acute ischemic stroke (AIS). An embedded process evaluation explored integration and impact of the intervention on care processes at participating US sites., Methods: A mixed-methods approach with quantitative and qualitative data were collected between September 2021 and November 2022. Implementer surveys were undertaken at pre- and post-intervention phases to understand the perceptions of low-intensity monitoring strategy. A sample of stroke care nurses were invited to participate in semi-structured interviews at an early stage of post-intervention. Qualitative data were analyzed deductively using the normalization process theory; quantitative data were tabulated., Results: Interviews with 21 nurses at 8 hospitals have shown low-intensity monitoring was well accepted, as there were less time constraints and reduced workload for each patient. There were initial safety concerns over missing deteriorating patients and difficulties in changing established routines. Proper training, education, and communication, and changing the habits and culture of care, were key elements to successfully adopting the new monitoring care into routine practice. Similar results were found in the post-intervention survey (42 nurses from 13 hospitals). Nurses reported time being freed up to provide patient education (56%), daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (i.e. communication, family support)., Conclusions: Low-intensity monitoring for patients with mild-to-moderate acute ischemic stroke, facilitated by appropriate education and organizational support, appears feasible and acceptable at US hospitals., (S. Karger AG, Basel.)

Background: Although people with aphasia (PwA) represent 30% of stroke survivors, they are frequently excluded from stroke research, or their inclusion is unclear. Such practice significantly limits the generalizability of stroke research, increases the need to duplicate research in aphasia-specific populations, and raises important ethical and human rights issues., Objective: To detail the extent and nature of inclusion of PwA in contemporary stroke randomized controlled trials (RCTs)., Methods: We conducted a systematic search to identify completed stroke RCTs and RCT protocols published in 2019. Web of Science was searched using terms "stroke" and "randomized controlled trial". These articles were reviewed by extracting rates of PwA inclusion/exclusion, whether "aphasia" or related terms were referred to in the article or supplemental files, eligibility criteria, consent procedures, adaptations made to support the inclusion of PwA, and attrition rates of PwA. Data were summarized, and descriptive statistics applied when appropriate., Results: 271 studies comprising 215 completed RCTs and 56 protocols were included. 36.2% of included studies referred to aphasia/dysphasia. Of completed RCTs, only 6.5% explicitly included PwA, 4.7% explicitly excluded PwA, and inclusion was unclear in the remaining 88.8%. Among RCT protocols, 28.6% of studies intended inclusion, 10.7% intended excluding PwA, and in 60.7%, inclusion was unclear. In 45.8% of included studies, sub-groups of PwA were excluded, either explicitly (ie, particular types/severities of aphasia, eg, global aphasia) or implicitly, by way of ambiguous eligibility criteria which could potentially relate to a sub-group of PwA. Little rationale for exclusion was provided. 71.2% of completed RCTs did not report any adaptations that could support the inclusion of PwA, and minimal information was provided about consent procedures. Where it could be determined, attrition of PwA averaged 10% (range 0%-20%)., Conclusion: This paper details the extent of inclusion of PwA in stroke research and highlights opportunities for improvement., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The structured, clinically supervised withdrawal of medicines, known as deprescribing, is one strategy to address inappropriate polypharmacy. This study aimed to evaluate the costs and consequences of deprescribing in frail older people living in residential aged care facilities (RACFs) in Australia., Design: A within-trial cost-consequence analysis of a deprescribing intervention-Opti-Med. The Opti-Med double-blind randomized controlled trial of deprescribing included 3 groups: blinded control, blinded intervention, and an open intervention group., Setting and Participants: Seventeen RACFs in Western Australia and New South Wales. Participants were 303 older people living in participating RACFs from March 2014 to February 2019., Methods: Analysis was conducted from the health sector perspective. Health economic outcomes assessed include cost saved from deprescribed medicines and the incremental quality-adjusted life-years. Costs were presented in 2022 Australian dollars., Results: The total cost of the Opti-Med intervention was $239.13 per participant. The costs saved through deprescribed medicines over 12 months after adjusting for mortality within the trial period was $328.90 per participant in the blinded intervention group and $164.00 per participant in the open intervention group. On average, the cost of the intervention was more than offset by the cost saved from deprescribed medicines. Extrapolating these findings to the Australian population suggests a potential net cost saving of about $1 to $16 million per annum for the health system nationally. The incremental quality-adjusted life-years were very similar across the 3 groups within the trial period., Conclusions and Implications: Deprescribing for frail older people living in RACFs can be a cost-saving intervention without reducing the quality of life. Systemwide implementation of deprescribing across RACFs in Australia has the potential to improve health care delivery through the cost savings, which could be reapplied to further optimize care within RACFs., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications., Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS &lt;10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events., Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown., Methods: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database., Results: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database., Conclusions: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079., Competing Interests: Disclosures Dr You holds the Gusu Health Talents Program (GSWS2020029), Jiangsu Provincial Medical Key Discipline (ZDXK202217), and the 6th Jiangsu Province 333 High Level Talents Training Project. Dr Ouyang reports grant funding from The Medical Research Future Fund. Dr Wang holds an investigator grant from the National Health and Medical Research Council (NHMRC) of Australia. Dr Arima reports grants and personal fees from Daiichi Sankyo, grants and personal fees from Takeda, nonfinancial support from Phillips, and personal fees from Bayer, Fukuda Denshi, Merck Sharp and Dohme, Teijin, and Kyowa Kirin outside the submitted work. Dr Lindley holds an investigator grant from the NHMRC of Australia. Dr Robinson is an National Institute for Health Research Senior Investigator and reports grants from British Heart Foundation during the conduct of the study. Dr Anderson holds an NHMRC Senior Investigator Fellowship and reports grant funding from NHMRC, Penumbra, and Takeda China. Dr Chalmers reports grants from NHMRC outside the submitted work. The other authors report no conflicts.

Introduction: Rapid translation of research findings into clinical practice through innovation is critical to improve health systems and patient outcomes. Access to efficient systems of learning underpinned with real-time data are the future of healthcare. This type of health system will decrease unwarranted clinical variation, accelerate rapid evidence translation, and improve overall healthcare quality., Methods: This paper aims to describe The HARMONY model (acHieving dAta-dRiven quality iMprovement to enhance frailty Outcomes using a learNing health sYstem), a new frailty learning health system model of implementation science and practice improvement. The HARMONY model provides a prototype for clinical quality registry infrastructure and partnership within health care., Results: The HARMONY model was applied to the Western Sydney Clinical Frailty Registry as the prototype exemplar. The model networks longitudinal frailty data into an accessible and useable format for learning. Creating local capability that networks current data infrastructures to translate and improve quality of care in real-time., Conclusion: This prototype provides a model of registry data feedback and quality improvement processes in an inpatient aged care and rehabilitation hospital setting to help reduce clinical variation, enhance research translation capacity, and improve care quality., Competing Interests: The authors declare that they have no conflicts of interests., (© 2023 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Little is known on how lifestyle factors, individually or in combination, may relate to nursing home admission, an outcome of great societal and economic importance with increased population ageing. The aim of this study was to determine the association of lifestyle risk factors with nursing home admission., Methods: This prospective cohort study linked data from the 45 and Up Study, Australia, to health records. 127 108 men and women, aged ≥60 years, were recruited between 2006 and 2009. A healthy lifestyle score categorised participants into three risk groups based on five equally contributing risk factors: smoking status, physical activity, sedentary behaviour, sleep duration and diet quality. HRs for incident nursing home admission were estimated using multivariable Cox proportional hazards model., Results: One-quarter of participants were in the low-risk lifestyle group, 62% were in the medium-risk group and 14% in the high-risk (least healthy) group. During a median (IQR) follow-up of 11.3 years, 23 094 (18%) participants were admitted to a nursing home. Compared with those in the low-risk group, risk of nursing home admission was 43% higher among participants in the high-risk group (multivariable adjusted HR (aHR) 1.43; 95% CI 1.36 to 1.50); and participants in the medium-risk group had an intermediate 12% greater risk (aHR 1.12; 95% CI 1.08 to 1.16). Participants aged 60-64 years in the high-risk (aHR 2.15; 95% CI 1.82 to 2.54) lifestyle group had the greatest risk of nursing home admission., Conclusion: An unhealthy lifestyle was associated with a marked increased risk of admission to a nursing home in adults aged 60+ years. Interventions focused on lifestyle modifications may prevent or delay nursing home admission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The cause of the most common form of dementia, sporadic Alzheimer's disease (AD), remains unknown. This may reflect insufficiently powered studies to date for this multi-factorial disorder. The UK Biobank dataset presents a unique opportunity to rank known risk factors and determine novel variables., Methods: A custom machine learning approach for high dimensionality data was applied to explore prospectively associations between AD in a sub-cohort of 156,209 UK Biobank participants aged 60-70 including more than 2,090 who were subsequently diagnosed with AD., Results: After the possession of the APOE4 allele, the next highest ranked risk factors were other genetic variants within the TOMM40-APOE-APOC1 locus. When stratified by their apolipoprotein epsilon 4 (APOE4) carrier status, the most prominent risk factors in carriers were AST:ALT ratio, the "number of treatments/ medications" taken as well as "time spent in hospital" while protection was conferred by "Sleeplessness/Insomnia". In non-APOE carriers, lower socioeconomic status and fewer years of education were highly ranked but effect sizes were small relative to APOE4 carriers., Conclusions: Possession of the APOE4 allele was confirmed as the most important risk factor in AD. Other TOMM40-APOE-APOC1 locus variants further moderate the risk of AD in APOE4 carriers. Liver pathology is a novel risk factor in APOE4 carriers while "Sleeplessness/Insomnia" is protective in AD irrespective of APOE4 status. Other factors such as "Number of treatments/ medications" suggest that multimorbidity is an important risk factor for AD. Future treatments aimed at co-morbidities, including liver disease, may concomitantly lower the risk of sporadic AD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: To investigate the trial-based cost-effectiveness of the addition of a tailored digitally enabled exercise intervention to usual care shown to be clinically effective in improving mobility in the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial compared to usual care alone., Design: Economic evaluation alongside a pragmatic randomized controlled trial., Participants: 300 people receiving inpatient aged and neurological rehabilitation were randomized to the intervention ( n  = 149) or usual care control group ( n  = 151)., Main Measures: Incremental cost effectiveness ratios were calculated for the additional costs per additional person demonstrating a meaningful improvement in mobility (3-point in Short Physical Performance Battery) and quality-adjusted life years gained at 6 months (primary analysis). The joint probability distribution of costs and outcomes was examined using bootstrapping., Results: The mean cost saving for the intervention group at 6 months was AU$2286 (95% Bootstrapped cost CI: -$11,190 to $6410) per participant; 68% and 67% of bootstraps showed the intervention to be dominant (i.e. more effective and cost saving) for mobility and quality-adjusted life years, respectively. The probability of the intervention being cost-effective considering a willingness to pay threshold of AU$50,000 per additional person with a meaningful improvement in mobility or quality-adjusted life year gained was 93% and 77%, respectively., Conclusions: The AMOUNT intervention had a high probability of being cost-effective if decision makers are willing to pay AU$50,000 per meaningful improvement in mobility or per quality-adjusted life year gained, and a moderate probability of being cost-saving and effective considering both outcomes at 6 months post randomization.

Background: potentially harmful polypharmacy is very common in older people living in aged care facilities. To date, there have been no double-blind randomised controlled studies of deprescribing multiple medications., Methods: three-arm (open intervention, blinded intervention and blinded control) randomised controlled trial enrolling people aged over 65 years (n = 303, noting pre-specified recruitment target of n = 954) living in residential aged care facilities. The blinded groups had medications targeted for deprescribing encapsulated while the medicines were deprescribed (blind intervention) or continued (blind control). A third open intervention arm had unblinded deprescribing of targeted medications., Results: participants were 76% female with mean age 85.0 ± 7.5 years. Deprescribing was associated with a significant reduction in the total number of medicines used per participant over 12 months in both intervention groups (blind intervention group -2.7 medicines, 95% CI -3.5, -1.9, and open intervention group -2.3 medicines; 95% CI -3.1, -1.4) compared with the control group (-0.3, 95% CI -1.0, 0.4, P = 0.053). Deprescribing regular medicines was not associated with any significant increase in the number of 'when required' medicines administered. There were no significant differences in mortality in the blind intervention group (HR 0.93, 95% CI 0.50, 1.73, P = 0.83) or the open intervention group (HR 1.47, 95% CI 0.83, 2.61, P = 0.19) compared to the control group., Conclusions: deprescribing of two to three medicines per person was achieved with protocol-based deprescribing during this study. Pre-specified recruitment targets were not met, so the impact of deprescribing on survival and other clinical outcomes remains uncertain., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We aimed to assess the association of atrial fibrillation (AF) on outcomes in a post hoc analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) and how this association is modified by baseline imaging features., Methods: Inverse probability of treatment weight was used to remove baseline imbalances between those with and without AF. The primary outcome was the modified Rankin Scale (mRS) scores at 90 days. Secondary outcomes were symptomatic intracerebral haemorrhage (sICH), early neurological deterioration or death within 24 h, and death at 90 days. The logistic regression model was used to determine the associations., Results: Of the 3285 patients included in this analysis, 636 (19%) had AF at baseline. Compared with non-AF, AF was not significantly associated with an unfavourable shift of mRS (odds ratio 1.09; 95% confidence interval, 0.96-1.24), but with sICH (2.82; 1.78-4.48; IST-3 criteria), early neurological deterioration or death within 24 h (1.31; 1.01-1.70), and death (1.42; 1.12-1.79). Among patients with acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions), AF was associated with the increased risk of all the poor outcomes (all P < 0.04 for interaction)., Conclusions: We found AF increased risk of sICH, early neurological deterioration or death and death, but not unfavourable functional recovery at day 90 after thrombolysis in patients with AIS. The presence of acute ischaemic brain imaging signs at stroke presentation could be used to improve risk stratification in the presence of AF., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT01422616)., (© 2023. The Author(s).)

Background: Deprescribing is an intervention to address the high prevalence of inappropriate polypharmacy in older people living in residential aged care facilities (RACFs). Many deprescribing interventions are complex and involve several stages including initial pharmacist recommendation, subsequent acceptance of the recommendations by a prescriber and the patient, and then actual implementation., Objectives: This study aimed to investigate pharmacist deprescribing recommendations for residents within RACFs, general practitioner (GP) acceptance, and the actual implementation of the accepted recommendations at 12-month., Methods: The intervention occurred as part of a randomised controlled trial and comprised a pharmacist-led medication review using an evidence-based algorithm, with the focus on identifying medications to potentially deprescribe. Consent to participate was obtained from residents (or surrogate decision-makers), RACF nursing staff and the resident's GP. Deprescribing recommendations were reviewed by GPs before implementation as part of the intervention and control arms of the trial, although control group participants continued to receive their usual medications in a blinded manner., Results: There were 303 participants enrolled in the study, and 77% (941/1222) of deprescribing recommendations suggested by the pharmacists were accepted by GPs. Of the recommendations accepted by GPs, 74% (692/ 941) were successfully implemented at the end of the follow-up visit at 12 months. The most common reason for deprescribing was because medications were no longer needed (42%, 513/ 1231)., Conclusion: Pharmacist-led deprescribing recommendations arising from an algorithm-based medication review are acceptable to doctors and can have a significant impact on reducing the number of inappropriate medications consumed by older people in RACFs., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613001204730., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130-140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target <180 mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018., Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24-36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616., Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24-36 h. Mean achieved systolic blood pressures over 1-24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24-36 h (0.3 [IQR 0.0-16.6] in the intensive group and 0.9 [0.0-12.5] in the guideline group; log Δmean -0.17, 95% CI -0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses., Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity., Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda., Competing Interests: GM received a research grant from the UK Stroke Association, and consulting fee and honoraria from Canon Medical. JB has received consulting fees from Roche, and honoraria on the Executive Committee for TIMELESS Trial from Genentech. AMD received grants from Medtronic and Circle CVI, and has received consulting fees and honoraria from HLS Therapeutics, Hoffmann LaRoche Servier, Astra Zeneca, and Boehringer Ingelheim. He is also a member on Data Safety and Monitoring Boards (DSMB) for Philips and Lumosa, and has a role on the Canadian Stroke Consortium and Canadian Partnership for Stroke Recovery. PB has received research grants from the UK Stroke Association, British Heart Foundation, NIHR HTA, and NUH Charity, and honoraria for advisory board activities from DiaMedica, Phagenesis, and Roche. He is also the Chair and Co-Chair of DSMBs for ESPS-2 and AVERT-Dose, respectively, and has stock from DiaMedica. AMD has stock from Circle CVI. RIL has received grants from the National Health and Medical Research Council (NHMRC). JC reports receiving a Program Grant the NHMRC from of Australia and is the Chair of the Steering Committee for ENCHANTED. SM has received grants from Ministry of Health PROADI SUS Hospital Moinhos de Vento, including RESILIENT Direct TNK, RESILIENT Extend IV, TRIDENT, and PROMOTE trials. She also received honoraria from Boehringer Ingelheim, Medtronic, Penumbra, Novartis, Novo Nordisk, Pfizer, Bayer, Servier, and Daiichi Sankyo, has participated on a DSMB for Johnson and Johnson's Executive Board for the Librexia clinical trial, and is the President of World Stroke Organisation and Brazilian Stroke Network. PMV has received a research grant from ANID Fondecyt Regular, Chile, and is member of the Scientific Advisors Committee to the Chilean Ministry of Sciences and Technology, for the COVID-19 vaccine national strategy. VVO has received a research grant from ANID Fondecyt Regular 1,181,333 Chile and a research grant from Boehringer Ingelheim. PL has received a research grant from ANID Fondecyt Regular, Chile, and honoraria from Boehringer Ingelheim, and has a role on a DSMB for Boehringer Ingelheim and the Chilean Ministry of Health, and is the President of the Chilean Stroke Association. CSA and LS received research grants from the NHMRC, MRC, Takeda China, and Penumbra. The other authors declare no competing interests., (© 2023 The Author(s).)

Objective: To describe medicines regimens used by older people living in residential aged care facilities (RACFs)., Materials and Methods: This cross-sectional study presents baseline data from a randomised controlled trial in seventeen Australian RACFs that recruited residents aged 65 years and older at the participating facilities. The main outcome measures were to evaluation of medicines utilisation, including the number of medicines, medicine regimen complexity, potential under-prescribing and high-risk prescribing (prescribing cascades, anticholinergic or sedative medicines or other potentially inappropriate medicines) with data analysed descriptively., Results: Medicines regimens were analysed for 303 residents (76% female) with a mean age of 85.0 ± 7.5 years, of whom the majority were living with dementia (72%). Residents were prescribed an average of 10.3 ± 4.5 regular medicines daily. Most participants (85%) had highly complex regimens. Most residents (92%) were exposed to polypharmacy (five or more medicines). Nearly all, 302 (98%) residents had at least one marker of potentially suboptimal prescribing. At least one instance of potential under-prescribing was identified in 86% of residents. At least one instance of high-risk prescribing was identified in 81% of residents including 16% of participants with at least one potential prescribing cascade., Conclusion(s): Potentially suboptimal prescribing affected almost all residents in this study, and most had highly complex medicines regimens. If generalisable, these findings indicate most older people in RACFs may be at risk of medicines-related harm from suboptimal prescribing, in addition to the burden of administration of complex medicines regimens for facility staff and residents., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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., Trial Registration: The protocol was registered with the Australian New Zealand Clinical Trials Registry (Trial Id: ACTRN12620000694910)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kairaitis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Real-world evidence is limited on whether antihypertensive medications help avert major adverse cardiovascular events (MACE) after stroke without increasing the risk of falls. We investigated the association of adherence to antihypertensive medications on the incidence of MACE and falls requiring hospitalization after stroke., Methods: A retrospective cohort study of adults who were newly dispensed antihypertensive medications after an acute stroke (Australian Stroke Clinical Registry 2012-2016; Queensland and Victoria). Pharmaceutical dispensing records were used to determine medication adherence according to the proportion of days covered in the first 6 months poststroke. Outcomes between 6 and 18 months postdischarge included: (i) MACE, a composite outcome of all-cause death, recurrent stroke or acute coronary syndrome; and (ii) falls requiring hospitalization. Estimates were derived using Cox models, adjusted for >30 confounders using inverse probability treatment weights., Results: Among 4076 eligible participants (median age 68 years; 37% women), 55% had a proportion of days covered ≥80% within 6 months postdischarge. In the subsequent 12 months, 360 (9%) participants experienced a MACE and 337 (8%) experienced a fall requiring hospitalization. After achieving balance between groups, participants with a proportion of days covered ≥80% had a reduced risk of MACE (hazard ratio: 0.68; 95% CI: 0.54-0.84) and falls requiring hospitalization (subdistribution hazard ratio: 0.78; 95% CI: 0.62-0.98) than those with a proportion of days covered <80%., Conclusions: High adherence to antihypertensive medications within 6 months poststroke was associated with reduced risks of both MACE and falls requiring hospitalization. Patients should be encouraged to adhere to their antihypertensive medications to maximize poststroke outcomes.

Background: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention., Objectives: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH., Design: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety., Results: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024., Conclusion: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

Objective: Western Sydney Local Health District (WSLHD) measured the utility and validity of rapid molecular point-of-care testing (POCT) in aged care facilities (ACFs) experiencing influenza-like illness (ILI) outbreaks against routine laboratory testing., Methods: A descriptive epidemiological study into 82 respiratory outbreaks reported across 63 ACFs within WSLHD supporting approximately 6,500 residents aged ≥65 years and staffed by ∼6,500 employees, from 1 August 2018 to 31 December 2019., Results: WSLHD Public Health Unit performed on-site testing at 27 ACF outbreaks (34%), while 53(66%) ACFs conducted only routine laboratory testing. The Xpert®Xpress Flu/RSV molecular PCR provided a sensitivity and specificity of 100%. Those with on-site testing, antiviral prophylaxis was prescribed at 75% of facilities within 24 hours of testing, as opposed to 32% of those using laboratory testing (p<0.01). There were 24 of 181 ACF residents hospitalised in the POCT group compared to 76 of 357 in the laboratory-only group (OR=0.57; p=0.02)., Conclusions: On-site ACF testing is reliable and practical for early identification of influenza, enabling timely use of antiviral treatment and prophylaxis, and was associated with decreased hospitalisation., Public Health Implications: Enhanced respiratory surveillance and on-site testing should be strongly considered as part of routine management of respiratory outbreaks in ACFs and may reduce outbreak severity., (© 2022 The Authors.)

People with aphasia have been systematically excluded from stroke research or included without the necessary modifications, threatening external study validity. In this paper, we propose that 1) the inclusion of people with aphasia should be considered as standard in stroke research irrespective of discipline and that 2) modifications should be made to stroke research procedures to support people with aphasia to achieve meaningful and valid inclusion. We argue that outright exclusion of this heterogenous population from stroke research based purely on a diagnosis of aphasia is rarely required and present a rationale for deliberate inclusion of people with aphasia in stroke research. The purpose of this paper is fourfold: 1) to highlight the issue and implications of excluding people with aphasia from stroke research; 2) to acknowledge the current barriers to including people with aphasia in stroke research; 3) to provide stroke researchers with methods to enable inclusion, including recommendations, resources, and guidance; and 4) to consider research needed to develop aphasia inclusive practices in stroke research., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Human metapneumovirus (hMPV), first described in 2001, is a cause of acute respiratory tract infection in the elderly, with symptoms ranging from mild to severe, including pneumonia, but outbreaks are rarely described., Methods: Between 1 July and 31 December 2018, there were three outbreaks of Influenza-like Illness (ILI) where hMPV was the primary pathogen observed, among 64 aged-care facilities (ACFs) in Western Sydney. These outbreaks were investigated by the Western Sydney Local Health District (WSLHD) Public Health Unit (PHU); multiplex polymerase chain reaction (PCR) testing was performed on nasopharyngeal swabs collected by the ACF., Results: hMPV was the main causative pathogen in three outbreaks (27, 28, and 15 symptomatic cases, respectively) in late winter and early spring. Fifty-five residents and 15 staff cases (70 total cases) were identified; hMPV was detected in 12 of 63 specimens submitted. Of the cases in residents, eight were hospitalised (8/63; 15%), including five with confirmed hMPV and a further one epidemiologically linked to a positive case. Six residents died (6/63; 11%) during the hMPV outbreaks; four of these had laboratory-confirmed hMPV, with a further case epidemiologically linked to a hMPV case, with a primary diagnosis of pneumonia/viral pneumonia. The sixth death was not epidemiologically linked, nor did this case exhibit any respiratory symptoms during the outbreak; however, it was reported in line with public health guidelines., Conclusion: A major challenge in 2018 was the incompleteness of testing for, and awareness of, hMPV as a viral cause of ILI by facilities, laboratories, and emergency departments, which generally opted for rapid testing for influenza and RSV only. There is no licensed vaccine or approved treatment for hMPV, so efficient infection control measures are most important., (© Commonwealth of Australia CC BY-NC-ND.)

Background: We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)., Methods: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models., Results: There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90]) but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], P interaction  = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], P interaction  = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], P interaction  = 0.05)., Conclusions: Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01422616.

Background: Obtaining informed consent in people with acute stroke is complex since many, as a direct result of their stroke, lose capacity to make important decisions. Furthermore, reperfusion interventions are time dependent necessitating rapid consent. We developed four different consent approaches to facilitate recruitment of a broad range of patients in the Third International Stroke Trial (IST-3)., Aims: To describe the clinical characteristics of patients recruited by different consent methods and the association between these methods and time from stroke onset to randomization., Methods: IST-3 was a randomized controlled trial of thrombolysis for acute ischemic stroke. Clinicians could use one of four consent procedures: written consent, witnessed consent, assent, or a waiver of consent. We analyzed the relationship between consent procedure and baseline variables. The effect of consent procedure on delay time from onset to randomization was determined using analysis of variance to adjust for confounding effects., Results: Of the 3035 patients recruited, the method of consent was known for 3034 (99.9%), and it was written in 985 subjects (32.5%), witnessed verbal consent in 280 (9.2%), assent by relative in 1727 (56.9%), and waiver of consent in 42 subjects (1.4%). Assent was required in 63.4% for those presenting 0-3 h from stroke onset (written consent in 25.3%). Patients with more severe neurological deficits (or with a non-lacunar hemispheric stroke syndrome) were less likely to give written consent. Mean delay between onset and randomization varied significantly between consent types (one-way analysis of variance: F = 15.7 on 3 df, p < 0.0001) (longest at 4.06 h for signed consent and 3.46 h for waiver of consent)., Conclusions: Acute stroke trials requiring written informed consent would result in substantial selection bias. Flexible consent methods will ensure a broad range of patients are recruited, enabling trial results to be widely generalizable. Registration: This study's registered number is ISRCTN25765518.

Introduction: Older people living with frailty and/or cognitive impairment who have coronavirus disease 2019 (COVID-19) experience higher rates of critical illness. There are also people who become critically ill with COVID-19 for whom a decision is made to take a palliative approach to their care. The need for clinical guidance in these two populations resulted in the formation of the Care of Older People and Palliative Care Panel of the National COVID-19 Clinical Evidence Taskforce in June 2020. This specialist panel consists of nursing, medical, pharmacy and allied health experts in geriatrics and palliative care from across Australia., Main Recommendations: The panel was tasked with developing two clinical flow charts for the management of people with COVID-19 who are i) older and living with frailty and/or cognitive impairment, and ii) receiving palliative care for COVID-19 or other underlying illnesses. The flow charts focus on goals of care, communication, medication management, escalation of care, active disease-directed care, and managing symptoms such as delirium, anxiety, agitation, breathlessness or cough. The Taskforce also developed living guideline recommendations for the care of adults with COVID-19, including a commentary to discuss special considerations when caring for older people and those requiring palliative care., Changes in Management as Result of the Guideline: The practice points in the flow charts emphasise quality clinical care, with a focus on addressing the most important challenges when caring for older individuals and people with COVID-19 requiring palliative care. The adult recommendations contain additional considerations for the care of older people and those requiring palliative care., (© 2021 The Authors.Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background and Purpose: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients., Methods: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage., Results: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P <0.001 and 0.86 [95% CI, 0.76-0.98]; P =0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P =0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P =0.002 and 1.34 [1.11-1.62]; P =0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P =0.184)., Conclusions: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Background: Atrial fibrillation (AF) is common in older people and increases the risk of stroke. The feasibility and effectiveness of the implementation of a patient-led AF screening program for older people are unknown., Objective: This study aims to examine the feasibility and effectiveness of an AF screening program comprising patient-led monitoring of single-lead electrocardiograms (ECGs) with clinician-coordinated central monitoring to diagnose AF among community-dwelling people aged ≥75 years in Australia., Methods: This is a nationwide randomized controlled implementation trial conducted via the internet and remotely among 200 community-dwelling adults aged ≥75 years with no known AF. Randomization will be performed in a 1:1 allocation ratio for the intervention versus control. Intervention group participants will be enrolled in the monitoring program at randomization. They will receive a handheld single-lead ECG device and training on the self-recording of ECGs on weekdays and submit their ECGs via their smartphones. The control group participants will receive usual care from their general practitioners for the initial 6 months and then commence the 6-month monitoring program. The ECGs will be reviewed centrally by trained personnel. Participants and their general practitioners will be notified of AF and other clinically significant ECG abnormalities., Results: This study will establish the feasibility and effectiveness of implementing the intervention in this patient population. The primary clinical outcome is the AF detection rate, and the primary feasibility outcome is the patient satisfaction score. Other outcomes include appropriate use of anticoagulant therapy, participant recruitment rate, program engagement (eg, frequency of ECG transmission), agreement in ECG interpretation between the device automatic algorithm and clinicians, the proportion of participants who complete the trial and number of dropouts, and the impact of frailty on feasibility and outcomes. We will conduct a qualitative evaluation to examine the barriers to and acceptability and enablers of implementation. Ethics approval was obtained from the human research ethics committee at the University of Sydney (project number 2020/680). The results will be disseminated via conventional scientific forums, including peer-reviewed publications and presentations at national and international conferences., Conclusions: By incorporating an integrated health care approach involving patient empowerment, centralized clinician-coordinated ECG monitoring, and facilitation of primary care and specialist services, it is possible to diagnose and treat AF early to reduce stroke risk. This study will provide new information on how to implement AF screening using digital health technology practicably and feasibly for older and frail populations residing in the community., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12621000184875; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380877., International Registered Report Identifier (irrid): DERR1-10.2196/34778., (©Kam Cheong Wong, Tu N Nguyen, Simone Marschner, Samual Turnbull, Mason Jenner Burns, Jia Yi Anna Ne, Vishal Gopal, Anupama Balasuriya Indrawansa, Steven A Trankle, Tim Usherwood, Saurabh Kumar, Richard I Lindley, Clara K Chow. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 01.02.2022.)

Background and Purpose: Changes to hospital systems were implemented from March 2020 in Australia in response to the coronavirus disease 2019 pandemic, including decreased resources allocated to stroke units. We investigate changes in the quality of acute care for patients with stroke or transient ischemic attack during the pandemic according to patients' treatment setting (stroke unit or alternate ward)., Methods: We conducted a retrospective cohort study of patients admitted with stroke or transient ischemic attack between January 2019 and June 2020 in the Australian Stroke Clinical Registry (AuSCR). The AuSCR monitors patients' treatment setting, provision of allied health and nursing interventions, prescription of secondary prevention medications, and discharge destination. Weekly trends in the quality of care before and during the pandemic period were assessed using interrupted time series analyses., Results: In total, 18,662 patients in 2019 and 8,850 patients in 2020 were included. Overall, 75% were treated in stroke units. Before the pandemic, treatment in a stroke unit was superior to alternate wards for the provision of all evidence-based therapies assessed. During the pandemic period, the proportion of patients receiving a swallow screen or assessment, being discharged to rehabilitation, and being prescribed secondary prevention medications decreased by 0.58% to 1.08% per week in patients treated in other ward settings relative to patients treated in stroke units. This change represented a 9% to 17% increase in the care gap between these treatment settings during the period of the pandemic that was evaluated (16 weeks)., Conclusions: During the first 6 months of the pandemic, widening care disparities between stroke units and alternate wards have occurred.

Purpose: To describe device use and physiotherapy support in the post-hospital phase of the AMOUNT rehabilitation trial., Methods: We performed an evaluation of the support required for device use by participants randomised to the intervention group who received digitally-enabled rehabilitation in the post-hospital phase ( n  = 144). Intervention, additional to standard rehabilitation, utilised eight digital devices (virtual reality videogames, activity monitors and handheld computer devices) to improve mobility and increase physical activity. Participants were taught to use devices during inpatient rehabilitation and were then discharged home to use the devices for the remainder of the 6-month trial. Physiotherapist-participant contact occurred every 1-2 weeks using a health coaching approach, including technology support when required. Intervention datasheets were audited, and descriptive statistics used to report device use and support required., Results: Participants (mean (SD) age 70 (18) years; 49% neurological health conditions) used an average of 2 (SD 1) devices (98% used an activity monitor). Eight percent of physiotherapy contact included technology support with 30% provided remotely. Support addressed 845 issues categorised under initial set-up and instruction (27%), education and training (31%), maintenance (23%) and trouble-shooting (19%)., Conclusion: Digital devices can be used for home-based rehabilitation, but ongoing technology support is essential. Clinical Trials Registry: ACTRN12614000936628IMPLICATIONS FOR REHABILITATIONDigital device use at home to support long-term management of health conditions is likely to become increasingly important as the need for rehabilitation increases and rehabilitation resources become more limited.Technology support for set-up and ongoing device use is a critical enabler of home-based digital interventions.Health professionals delivering home-based digital interventions require sufficient training and equipment and may need to vary the mode (e.g., home visit vs. telephone or video conference) depending on the technology support required.

Background and Purpose: Although a target of 80% medication adherence is commonly cited, it is unclear whether greater adherence improves survival after stroke or transient ischemic attack (TIA). We investigated associations between medication adherence during the first year postdischarge, and mortality up to 3 years, to provide evidence-based targets for medication adherence., Methods: Retrospective cohort study of 1-year survivors of first-ever stroke or TIA, aged ≥18 years, from the Australian Stroke Clinical Registry (July 2010–June 2014) linked with nationwide prescription refill and mortality data (until August 2017). Adherence to antihypertensive agents, statins, and nonaspirin antithrombotic medications was based on the proportion of days covered from discharge until 1 year. Cox regression with restricted cubic splines was used to investigate nonlinear relationships between medication adherence and all-cause mortality (to 3 years postdischarge). Models were adjusted for age, sex, socioeconomic position, stroke factors, primary care factors, and concomitant medication use., Results: Among 8363 one-year survivors of first-ever stroke or TIA (44% aged ≥75 years, 44% female, 18% TIA), 75% were supplied antihypertensive agents. In patients without intracerebral hemorrhage (N=7446), 84% were supplied statins, and 65% were supplied nonaspirin antithrombotic medications. Median adherence was ≈90% for each medication group. Between 1% and 100% adherence, greater adherence to statins or antihypertensive agents, but not nonaspirin antithrombotic agents, was associated with improved survival. When restricted to linear regions above 60% adherence, each 10% increase in adherence was associated with a reduction in all-cause mortality of 13% for antihypertensive agents (hazard ratio, 0.87 [95% CI, 0.81–0.95]), 13% for statins (hazard ratio, 0.87 [95% CI, 0.80–0.95]), and 15% for nonaspirin antithrombotic agents (hazard ratio, 0.85 [95% CI, 0.79–0.93])., Conclusions: Greater levels of medication adherence after stroke or TIA are associated with improved survival, even among patients with near-perfect adherence. Interventions to improve medication adherence are needed to maximize survival poststroke.

Background: Cardiovascular diseases (CVD), including myocardial infarction (MI), stroke and heart failure (HF) are the leading cause of death amongst the older population worldwide. The aim of this study is to investigate trajectories of use of health and aged care services after hospital admission for MI, stroke or HF among community-dwelling people not previously receiving aged care services., Methods: The study population comprised people aged 65+ years from the 45 and Up Study with linked records for hospital stays, aged care services and deaths for the period 2006-14. Among those with an index hospital admission for MI, stroke or HF, we developed Sankey plots to describe and visualize sequences and trajectories of service use (none, re-hospitalization, community care, residential care, death) in the 12 months following discharge. We used Cox proportional hazards models to estimate hazard ratios (HRs), for commencing community care and entering residential care (and the other outcomes) within 3, 6 and 12 months, compared to a matched group without MI, stroke or HF., Results: Two thousand six hundred thirty-nine, two thousand five hundred and two thousand eight hundred seventy-three people had an index hospitalization for MI, stroke and HF, respectively. Within 3 months of hospital discharge, 16, 32 and 29%, respectively, commenced community care (multivariable-adjusted HRs: 1.26 (95%CI:1.18-1.35), 1.53 (95%CI:1.44-1.64) and 1.39 (95%CI:1.32-1.48)); and 7, 18 and 14%, respectively, entered residential care (HRs: 1.25 (95%CI:1.12-1.41), 2.65 (95%CI:2.42-2.91) and 1.50 (95%CI:1.37-1.65)). Likewise, 26, 15 and 28%, respectively, were rehospitalized within 3 months following discharge (multivariable-adjusted HRs: 4.78 (95%CI:4.31-5.32), 3.26 (95%CI:2.91-3.65) and 4.94 (95%CI:4.47-5.46))., Conclusions: Older people hospitalized for major CVD may be vulnerable to transition-related risks and have poor health trajectories, thus emphasizing the value of preventing such events and care strategies targeted towards this at-risk group., (© 2021. The Author(s).)

Background and Purpose: As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke (AIS), we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)., Methods: Post-hoc analyses of ENCHANTED, an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS. Multivariable logistic regression models with inverse probability of treatment weighting (IPTW) propensity scores were used to determine associations of self-reported smoking status and clinical outcomes, according to 90-day modified Rankin Scale (mRS) scores and symptomatic intracerebral haemorrhage (sICH)., Results: Of 4540 patients who had an AIS, there were 1008 (22.2%) current smokers who were younger and predominantly male, with more comorbidities of hypertension, coronary artery disease, atrial fibrillation and diabetes mellitus, and greater baseline neurological impairment, compared with non-smokers. In univariate analysis, current smokers had a higher likelihood of a favourable shift in mRS scores (OR 0.88, 95% CI 0.77 to 0.99; p=0.038) but this association reversed in a fully adjusted model with IPTW (adjusted OR 1.15, 95% CI 1.04 to 1.28; p=0.009). A similar trend was also apparent for dichotomised poor outcome (mRS scores 2-6: OR 1.18, 95% CI 1.05 to 1.33; p=0.007), but not with the risk of sICH across standard criteria., Conclusion: Smoking predicts poor functional recovery in patients who had thrombolysed AIS., Trial Registration Number: NCT01422616., Competing Interests: Competing interests: RTL reports personal fees from Covidien and Pfizer; HA reports lecture fees from Takeda, Daiichi Sankyo, Astellas, and Aska Pharmaceuticals; outside the submitted work; JC reports research grants and lecture fees from Servier for the ADVANCE trial and post-trial follow-up; BO reports receiving fees for service on the data and safety monitoring committee of the THALES (ticagrelor) trial. CA reports personal lecture fees and travel support, and grants paid to his institution, from Takeda China., (© 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.)

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2-6, 3-5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management., (© 2021. The Author(s).)

Design: Descriptive., Setting: Community, Bangladesh., Objectives: To determine the costs associated with providing a community-based model of care delivered as part of the CIVIC trial to people discharged from hospital with recent spinal cord injury (SCI), and to determine the economic burden to households., Methods: Records were kept of the costs of providing a community-based model of care to participants of the CIVIC trial. Data were also collected at discharge and 2 years post discharge to capture out-of-pocket healthcare costs over the preceding 2 years, and the number of participants suffering catastrophic health expenditure and illness-induced poverty., Results: The mean cost of providing the community-based model of care to participants assigned to the intervention group (n = 204) was US$237 per participant. The mean out-of-pocket healthcare cost over the first 2 years post discharge was US$472 per participant (n = 410), and US$448 per control participant (n = 206). Median (IQR) equivalent annual household incomes prior to SCI and at 2 years post discharge were US$721 (US$452-1129) and US$464 (US$214-799), respectively. Of the 378 participants alive at 2 years, 324 (86%) had catastrophic health expenditure, and 161 of 212 participants who were not in poverty prior to injury (76%) were pushed into illness-induced poverty within 2 years of injury., Conclusion: The cost of providing community-based support to people with SCI for 2 years post discharge in Bangladesh is relatively inexpensive but an overwhelming majority of households rapidly experience financial catastrophe, and most fall into poverty., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background and Purpose: Conditions associated with frailty are common in people experiencing stroke and may explain differences in outcomes. We assessed associations between a published, generic frailty risk score, derived from administrative data, and patient outcomes following stroke/transient ischemic attack; and its accuracy for stroke in predicting mortality compared with other measures of clinical status using coded data., Methods: Patient-level data from the Australian Stroke Clinical Registry (2009–2013) were linked with hospital admissions data. We used International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes with a 5-year look-back period to calculate the Hospital Frailty Risk Score (termed Frailty Score hereafter) and summarized results into 4 groups: no-risk (0), low-risk (1–5), intermediate-risk (5–15), and high-risk (>15). Multilevel models, accounting for hospital clustering, were used to assess associations between the Frailty Score and outcomes, including mortality (Cox regression) and readmissions up to 90 days, prolonged acute length of stay (>20 days; logistic regression), and health-related quality of life at 90 to 180 days (quantile regression). The performance of the Frailty Score was then compared with the Charlson and Elixhauser Indices using multiple tests (eg, C statistics) for predicting 30-day mortality. Models were adjusted for covariates including sociodemographics and stroke-related factors., Results: Among 15 468 adult patients, 15% died ≤90 days. The frailty scores were 9% no risk; 23% low, 45% intermediate, and 22% high. A 1-point increase in frailty (continuous variable) was associated with greater length of stay (ORadjusted, 1.05 [95% CI, 1.04 to 1.06), 90-day mortality (HRadjusted, 1.04 [95% CI, 1.03 to 1.05]), readmissions (ORadjusted, 1.02 [95% CI, 1.02 to 1.03]; and worse health-related quality of life (median difference, −0.010 [95% CI −0.012 to −0.010]). Adjusting for the Frailty Score provided a slightly better explanation of 30-day mortality (eg, larger C statistics) compared with other indices., Conclusions: Greater frailty was associated with worse outcomes following stroke/transient ischemic attack. The Frailty Score provides equivalent precision compared with the Charlson and Elixhauser indices for assessing risk-adjusted outcomes following stroke/transient ischemic attack.

Objective: To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial., Research Design and Methods: Cox proportional hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI >0.21) status. The primary outcomes were macro- and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycemia, and discontinuation of BP treatment due to hypotension/dizziness., Results: There were 11,140 participants (mean age, 65.8 years; 42.5% women, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: hazard ratios for combined major macro- and microvascular events 1.03 (95% CI 0.90-1.19) in the frail versus 0.84 (95% CI 0.74-0.94) in the nonfrail ( P = 0.02). A similar trend was observed with BP intervention. Severe hypoglycemia rates (per 1,000 person-years) were higher in the frail: 8.39 (6.15-10.63) vs. 4.80 (3.84-5.76) in nonfrail ( P < 0.001). There was no significant difference in discontinuation of BP treatment between frailty groups., Conclusions: It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose-lowering and BP-lowering treatments., (© 2021 by the American Diabetes Association.)

Background: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association., Methods: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation., Results: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47)., Conclusion: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase., Competing Interests: Competing interests: RIL reports numerous grants during the conduct of the study as detailed in the supplemental material. PAGS reports non-financial support from Boehringer ingelheim, grants from Medical Research Council UK, during the conduct of the study. JMW reports grants from Medical Research Council, Stroke Association, The Health Foundation, Scottish Funding Council, Chief Scientist Office, and Chest, Heart & Stroke Scotland, during the conduct of the study; grants from British Heart Foundation (Edinburgh Centre for Research Excellence and LACI-2 trial), MRC UK Dementia Research Institute, Fondation Leducq (ref 16 CVD 05), EU Horizon 2020 (PHC-03-15, project No 666881), and ‘SVDs@Target’, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Study Design: Randomised controlled trial., Objectives: To determine the effectiveness of a sustainable community-based intervention designed to prevent serious complications and death 2 years after discharge in people with spinal cord injury in Bangladesh., Setting: Bangladesh., Methods: A pragmatic randomised controlled trial was undertaken. People who had sustained a spinal cord injury in the preceding 2 years, were wheelchair-dependent, and were about to be discharged from hospital in Bangladesh were recruited and randomised to an Intervention or Control group using a concealed allocation procedure stratified by level of lesion (tetraplegia/paraplegia). Participants in the Intervention group received 36 phone calls and three home visits over the first 2 years following discharge. All participants received usual post-discharge care. Survival status and date of death were determined by blinded assessors 2 years after randomisation., Results: Between July 2015 and March 2018, 410 participants were randomised (204 to Intervention, 206 to Control). There was no loss to follow up. At 2 years, 15 (7.4%) participants in the Intervention group and 16 (7.8%) participants in the Control group had died (hazard ratio from unadjusted Cox model = 0.93 [95% CI, 0.46 to 1.89]; p from log rank test 0.85). There were no clinically important or statistically significant average causal effects of intervention on the incidence or severity of complications., Conclusion: A program of community-based care for people with recent spinal cord injury in Bangladesh involving frequent phone contact and occasional in-person contact with a health professional after discharge from hospital is no better at preventing death at 2 years than usual care.

Purpose: CT attenuation of ischemic brain reduces with time after stroke onset. We aimed to quantify this relationship and test the feasibility and accuracy of estimating stroke onset time using only CT attenuation of visible ischemic lesions, the CT-Clock Tool., Methods: We selected CT scans with ischemic lesions representing a range of stroke-onset-to-scan times (elapsed time) from a well-defined stroke trial. We measured the attenuation of ischemic lesions and contralateral normal brain to derive attenuation ratio. We assigned scans to development (75%) or test (25%) datasets. We plotted the relationship between attenuation ratio and elapsed time in the development dataset and derived a best-fit curve. We calculated estimated time in the test dataset using only the attenuation ratio curve. We compared estimated time to elapsed time and derived absolute error for estimated time. We assessed area under the receiver operating characteristic (AUROC) curve for identifying scans ≤ 4.5 h elapsed time., Results: We included 342 scans from 200 patients (41% male, median age 83 years). Elapsed time range: 22 min to 36 days. Estimation errors were least at early elapsed times (r = 0.82, p < 0.0001): median absolute error was 23, 106, 1030 and 1933 min for scans acquired ≤ 3, > 3-9, > 9-30 and > 30 h from stroke onset, respectively. AUROC was high at 0.955., Conclusions: It is feasible to accurately estimate stroke onset time using simple attenuation measures of ischemic brain. Our method was most accurate 0-9 h from onset and may be useful for treatment eligibility assessment, especially where imaging resources are limited.

Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus., Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis., Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR pooled , 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HR pooled , 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HR pooled , 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HR pooled , 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HR pooled , 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate ( P =0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m 2 ]) subgroup (HR pooled , 0.50 [95% CI, 0.31-0.79])., Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.

Non-valvular atrial fibrillation is becoming more common in Australia and globally The direct oral anticoagulants apixaban, dabigatran and rivaroxaban offer an improved safety profile over warfarin Patient preferences are important and shared decision-making supports better adherence to treatment., Competing Interests: Conflicts of interest: none declared, ((c) NPS MedicineWise.)