Australian and New Zealand nursing and midwifery educators' planetary health knowledge, views, confidence and teaching practices: A descriptive survey study.

AIM: To explore Australian and New Zealand nursing and midwifery educators' planetary health knowledge, views, confidence and teaching practices. DESIGN: A cross-sectional survey design. METHODS: An online survey was sent to Australian and New Zealand nursing and midwifery educators across the 45 Schools of Nursing and Midwifery between July and September 2023. The online survey consisted of 29 open- and closed-ended questions about nursing and midwifery educators' planetary health knowledge, views, confidence and teaching practices. RESULTS: There was a total of 127 responses to the first open-ended question. A total of 97 nursing and midwifery educators then completed the remaining questions. While educators had mostly positive views about integrating planetary health into their teaching, they lacked the knowledge and/or confidence to do so effectively. CONCLUSION: Australian and New Zealand nursing and midwifery educators acknowledge that planetary health should be included in nursing and midwifery curricula, but most reported a deficit in knowledge and/or confidence to integrate these complex concepts into their teaching. When considering planetary health, most educators focussed on climate change, which demonstrates their limited understanding of the concept of planetary health. IMPLICATIONS FOR THE PROFESSION: All nurses and midwives need to understand how the health of the planet and human civilization are interconnected and be prepared to address complex global health challenges now and in the future. Across the world, key healthcare organizations have called upon nursing and midwifery educators to prepare the healthcare workforce to practice in a more sustainable way, including supporting decarbonization of healthcare. However, our study has demonstrated that nursing and midwifery educators do not feel ready to respond due to a lack of required knowledge and/or confidence. REPORTING METHOD: We used the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Achieving consensus on the essential knowledge and skills needed by nursing students to promote planetary health and sustainable healthcare: A Delphi study.

AIM: To achieve consensus on the knowledge and skills that undergraduate/pre-licensure nursing students require to steward healthcare towards a more sustainable future. DESIGN: A two-phase real-time Delphi study. METHODS: Phase 1 included the generation of Planetary Health, climate change and sustainability knowledge and skill statements based on a review of relevant literature. Phase 2 consisted of a real-time Delphi survey designed to seek consensus on the proposed statements from a panel of 42 international experts. RESULTS: Of the 49 survey statements, 44 (90%) achieved ≥75% consensus and 26 (53%) achieved ≥80% consensus. Three were removed and 32 were modified to improve clarity of language. CONCLUSION: The knowledge and skills statements that emerged through this Delphi study can serve as a guide for incorporating Planetary Health, climate change and sustainability into nursing education programs. IMPLICATIONS FOR THE PROFESSION: Incorporating Planetary Health and climate change education into nursing programs has the potential to produce more environmentally conscious and socially responsible nurses. IMPACT: The absence of consensus on the essential knowledge and skills expected of nursing students has hindered the advancement of curricula and impacted educators' confidence in teaching Planetary Health and climate change. This study has resulted in a meticulously crafted framework of knowledge and skill statements that will be beneficial to educators, the future nursing workforce, and, ultimately, the individuals and communities whom nurses serve. REPORTING METHOD: This paper adheres to the Conducting and REporting DElphi Studies (CREDES) reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Scholarly literature on nurses and pharmacogenomics: A scoping review.

BACKGROUND: Pharmacogenomics is the bioscience investigating how genes affect medication responses. Nurses are instrumental in medication safety. Pharmacogenomics is slowly being integrated into healthcare, and knowledge and understanding of it is now pertinent to nursing practice. PURPOSE: This paper aims to map the scholarly literature on pharmacogenomics in relation to nurses. METHODS: A scoping review was conducted in four databases: CINAHL, Embase (Ovid), ProQuest Health and Medicine and PubMed using the search terms pharmacogenomic*, pharmacogenetic*, PGx*, and nurs*, resulting in 263 articles of which 77 articles met the inclusion criteria. FINDINGS: Most articles (85 %, n = 65) were non-empirical and 12 presented empirical data (15 %, n = 12). The articles were USA-centric (81 %, n = 62) and represented a broad range of nursing specialties. CONCLUSION: The majority of scholarly literature on nurses and pharmacogenomics is narrative reviews. Further empirical research is warranted to investigate nurses' current knowledge levels and potential involvement with pharmacogenomics in clinical practice.

Scaling behaviours of deep learning and linear algorithms for the prediction of stroke severity.

Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 105-107 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such stroke outcome predictions however could be particularly instrumental in guiding acute clinical and rehabilitation care decisions. We here compared the capacities of classically used linear and novel deep learning algorithms in their prediction of stroke severity. Our analyses relied on a total of 1430 patients assembled from the MRI-Genetics Interface Exploration collaboration and a Massachusetts General Hospital-based study. The outcome of interest was National Institutes of Health Stroke Scale-based stroke severity in the acute phase after ischaemic stroke onset, which we predict by means of MRI-derived lesion location. We automatically derived lesion segmentations from diffusion-weighted clinical MRI scans, performed spatial normalization and included a principal component analysis step, retaining 95% of the variance of the original data. We then repeatedly separated a train, validation and test set to investigate the effects of sample size; we subsampled the train set to 100, 300 and 900 and trained the algorithms to predict the stroke severity score for each sample size with regularized linear regression and an eight-layered neural network. We selected hyperparameters on the validation set. We evaluated model performance based on the explained variance (R2) in the test set. While linear regression performed significantly better for a sample size of 100 patients, deep learning started to significantly outperform linear regression when trained on 900 patients. Average prediction performance improved by ∼20% when increasing the sample size 9× [maximum for 100 patients: 0.279 ± 0.005 (R2, 95% confidence interval), 900 patients: 0.337 ± 0.006]. In summary, for sample sizes of 900 patients, deep learning showed a higher prediction performance than typically employed linear methods. These findings suggest the existence of non-linear relationships between lesion location and stroke severity that can be utilized for an improved prediction performance for larger sample sizes.

Promoting sustainability in nursing and midwifery clinical laboratories: Strategies for resource reduction, reuse, and recycling.

BACKGROUND: The impacts of climate change on planetary health are multifaceted and threaten public health gains made since World War II. Healthcare is the fifth largest global emitter of greenhouse gas emissions, demanding significant efforts to transition to an environmentally sustainable future. Addressing these issues will require collective societal action. In this regard, universities have a dual responsibility - (1) to tackle complex social, economic, and environmental challenges by championing sustainability initiatives designed to positively impact planetary health; and (2) to ensure that graduates are equipped with the knowledge, attitudes and skills needed to steward planetary health towards a more sustainable future. The future nursing and midwifery workforce must be educated to mitigate the health sector's impact on the environment, advocate for action on climate change, prepare for ongoing health impacts of unpredictable climate and environmental changes, and help communities and healthcare systems become more climate resilient. WHAT THIS PAPER CONTRIBUTES: To help increase nursing and midwifery educators' and students' capacity to support planetary-health related interventions, the overarching purpose of this paper is to provide a series of exemplars that illustrate sustainability initiatives used in four university-based clinical skills laboratories. These initiatives each demonstrate a commitment to the United Nation's Sustainable Development Goals and can be used to help embed the importance of planetary health in student learning.

Linguistic Validation of Genomic Nursing Concept Inventory to Finnish Applying Mandysova's Decision Tree Algorithm.

Background and Purpose: Currently, there is no available Finnish version of the Genomic Nursing Concept Inventory tool (GNCI). This study tested the validity, reliability, and clinical usability of a Finnish translation. Methods: A decision tree algorithm was used to guide the translation, as per International Society for Pharmacoeconomics and Outcomes Research guidelines. Item-Content Validity Index (I-CVI), modified kappa (k*) statistics, and Cronbach's alpha were calculated. Results: The I-CVI and k* values were "good" to "excellent" (I-CVI = 0.63-1.00, k* = 0.52-1.00), and Cronbach's alpha value was "good" (α = 0.816; 95% confidence interval: 0.567-0.956). Conclusion: The Mandysova's decision tree algorithm provided clear and rigorous direction for the translation and validity of the Finnish GNCI.

The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics.

Background purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort. Materials and methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome. Results: We analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, p FDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, p FDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL. Conclusion: Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

The association between fatigue severity and risk of falls among middle-aged and older Australian stroke survivors.

BACKGROUND: Fatigue is a common and often debilitating symptom experienced by many stroke survivors. Significant post stroke fatigue may predispose individuals to other health complications, such as falls, which can lead to fractures and soft tissue injuries. Only limited research has examined the association between fatigue and falls in stroke survivors. METHODS: Data were obtained from the Sax Institute's 45 and Up Study, from a subset of individuals who had experienced a stroke. The Modified Fatigue Impact Scale-5-item version (MFIS-5) was used to measure the level of fatigue. A logistic regression model, adjusted for stroke characteristics and comorbidities, was used to determine the magnitude of association between change in fatigue score and odds of having had a fall. RESULTS: A total of 576 participants completed the questionnaire. A total of 214 (37.2%) participants reported having had a fall in the previous 12 months. There was a statistically significant association between fatigue scores and fall status (p < 0.001). Specifically, for every 1-point increase in the fatigue score (MFIS-5) (i.e. higher level of fatigue), the odds of a person having a fall is 1.10 times greater (AOR = 1.10; 95% CI 1.05, 1.15; p < 0.001). CONCLUSION: This study revealed an association between an increasing risk of falls with increasing severity of post stroke fatigue. Accurate detection and management of fatigue may help reduce the risk of falls and should be the focus of future research.

Associations Between Fatigue and Disability, Depression, Health-Related Hardiness and Quality of Life in People with Stroke.

BACKGROUND: Stroke is a common cause of mortality and morbidity which affects approximately 17 million people globally each year. Common symptoms associated with stroke are physical disabilities, impaired cognitive functions, depression, and fatigue, all of which can significantly impact health-related quality of life (HRQoL). To date, no research has explored the inter-relationship among fatigue, disability, depression, health-related hardiness, and quality of life in stroke survivors. METHODS: Data was obtained from a sub-study of the 45 and Up Study; including 576 Australian adults who had been diagnosed with a stroke. The cross-sectional questionnaire obtained demographic and health status information, as well as clinical measures and stroke-related measures. Associations among fatigue and disability, depression, health-related hardiness and quality of life were analysed using a linear regression model. RESULTS: In comparison to those participants with no stroke-related disability, those with slight (ß = 1.141; p = 0.008), moderate (ß = 3.250; p < 0.001) or severe (ß = 3.526; p < 0.001) disability had significantly higher fatigue scores. For every one unit increase in the depression score, the fatigue score increased by 1.502 points (p < 0.001). For every one unit increase in the health-related hardiness score, the fatigue score decreased by 0.054 points (p = 0.044). For every one unit increase in the quality of life score, the fatigue score decreased by 0.068 points (p < 0.001). CONCLUSION: This study found significant associations among fatigue and disability, depression, health-related hardiness, and quality of life in stroke survivors. Accurate detection and management of fatigue may help improve the rehabilitation of stroke survivors.

International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery.

Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.

Genetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Stroke.

BACKGROUND AND OBJECTIVES: To test the hypothesis that a predisposition to acquired genetic alterations is associated with ischemic stroke outcome by investigating the association between a polygenic risk score (PRS) for mosaic loss of chromosome Y (mLOY) and outcome in a large international data set. METHODS: We used data from the genome-wide association study performed within the Genetics of Ischemic Stroke Functional Outcome network, which included 6,165 patients (3,497 men and 2,668 women) with acute ischemic stroke of mainly European ancestry. We assessed a weighted PRS for mLOY and examined possible associations with the modified Rankin Scale (mRS) score 3 months poststroke in logistic regression models. We investigated the whole study sample as well as men and women separately. RESULTS: Increasing PRS for mLOY was associated with poor functional outcome (mRS score >2) with an odds ratio (OR) of 1.11 (95% confidence interval [CI] 1.03-1.19) per 1 SD increase in the PRS after adjustment for age, sex, ancestry, stroke severity (NIH Stroke Scale), smoking, and diabetes mellitus. In sex-stratified analyses, we found a statistically significant association in women (adjusted OR 1.20, 95% CI 1.08-1.33). In men, the association was in the same direction (adjusted OR 1.04, 95% CI 0.95-1.14), and we observed no significant genotype-sex interaction. DISCUSSION: In this exploratory study, we found associations between genetic variants predisposing to mLOY and stroke outcome. The significant association in women suggests underlying mechanisms related to genomic instability that operate in both sexes. These findings need replication and mechanistic exploration.

Are clinicians using routinely collected data to drive practice improvement? A cross-sectional survey.

BACKGROUND: Clinical registry participation is a measure of healthcare quality. Limited knowledge exists on Australian hospitals' participation in clinical registries and whether this registry data informs quality improvement initiatives. OBJECTIVE: To identify participation in clinical registries, determine if registry data inform quality improvement initiatives, and identify registry participation enablers and clinicians' educational needs to improve use of registry data to drive practice change. METHODS: A self-administered survey was distributed to staff coordinating registries in seven hospitals in New South Wales, Australia. Eligible registries were international-, national- and state-based clinical, condition-/disease-specific and device/product registries. RESULTS: Response rate was 70% (97/139). Sixty-two (64%) respondents contributed data to 46 eligible registries. Registry reports were most often received by nurses (61%) and infrequently by hospital executives (8.4%). Less than half used registry data 'always' or 'often' to influence practice improvement (48%) and care pathways (49%). Protected time for data collection (87%) and benchmarking (79%) were 'very likely' or 'likely' to promote continued participation. Over half 'strongly agreed' or 'agreed' that clinical practice improvement training (79%) and evidence-practice gap identification (77%) would optimize use of registry data. CONCLUSIONS: Registry data are generally only visible to local speciality units and not routinely used to inform quality improvement. Centralized on-going registry funding, accessible and transparent integrated information systems combined with data informed improvement science education could be first steps to promote quality data-driven clinical improvement initiatives.

Ensuring best practice in genomics education and evaluation: reporting item standards for education and its evaluation in genomics (RISE2 Genomics).

PURPOSE: Widespread, quality genomics education for health professionals is required to create a competent genomic workforce. A lack of standards for reporting genomics education and evaluation limits the evidence base for replication and comparison. We therefore undertook a consensus process to develop a recommended minimum set of information to support consistent reporting of design, development, delivery, and evaluation of genomics education interventions. METHODS: Draft standards were derived from literature (25 items from 21 publications). Thirty-six international experts were purposively recruited for three rounds of a modified Delphi process to reach consensus on relevance, clarity, comprehensiveness, utility, and design. RESULTS: The final standards include 18 items relating to development and delivery of genomics education interventions, 12 relating to evaluation, and 1 on stakeholder engagement. CONCLUSION: These Reporting Item Standards for Education and its Evaluation in Genomics (RISE2 Genomics) are intended to be widely applicable across settings and health professions. Their use by those involved in reporting genomics education interventions and evaluation, as well as adoption by journals and policy makers as the expected standard, will support greater transparency, consistency, and comprehensiveness of reporting. Consequently, the genomics education evidence base will be more robust, enabling high-quality education and evaluation across diverse settings.

Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.

Rationale: More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success. Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early. Methods: This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders. Outcomes: The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study. Discussion: If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.

Randomized controlled trial on the effectiveness of web-based Genomics Nursing Education Intervention for undergraduate nursing students: a study protocol.

AIM: To describe a randomized controlled trial protocol that will evaluate the effectiveness of two web-based genomic nursing education interventions. BACKGROUND: Preparing future nurses to be competent in genetic and genomic concepts is fundamental to ensure appropriate clinical application. However, genetics-genomics concepts are still new in the field of nursing. Little is known about what type and kind of web-based nursing education is effective in improving the knowledge of nursing students. To address these knowledge gaps, a web-based 'Genomic Nursing Education Intervention' will be developed and compared with an existing online education programme. DESIGN: A randomized controlled trial of two groups with pre-test and repeated posttesting. METHODS: The Genomic Nursing Concept Inventory, a validated tool, will be used to assess the genetics-genomics knowledge of nursing students. Participants will be randomly allocated to either a control or an intervention group. The control group will receive the standard web-based nursing education, while the intervention group will receive a newly developed web-based education intervention. Outcome measures include the students' knowledge level of nursing genetics-genomics concepts. Participants will be retested at 3 and 6 months. CONCLUSION: Current evidence shows that ensuring nurses have adequate education in genetic-genomic concepts is challenging. This study will demonstrate which of two web-based nursing education methods is more effective in teaching genetic-genomic concepts. This research project will better prepare the nursing profession in their careers for the emerging advance technologies in genetics-genomics and personalized health care. IMPACT: Current evidence shows major challenges in ensuring that nurses have adequate education in genetics-genomics concepts. Less is known about what approaches to web-based education are effective to improve the knowledge gaps of nursing students in genetics-genomics concepts. This study will determine which type of web-based nursing education is effective in improving the genetics-genomics knowledge of nursing students. This research project will help better prepare nurses in dealing with advances in genetics-genomics in their careers. TRIAL REGISTRATION:  This study is registered in ClinicalTrials.gov (ID number NCT03963687) https://clinicaltrials.gov/show/NCT03963687.

Brain Volume: An Important Determinant of Functional Outcome After Acute Ischemic Stroke.

OBJECTIVE: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). PATIENTS AND METHODS: This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. RESULTS: Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (ß -0.3 [per 14.4 years]), male sex (ß 1.0), and prior stroke (ß -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (ß -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. CONCLUSION: Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception. METHODS AND ANALYSIS: The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0-2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design. ETHICS AND DISSEMINATION: Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.

The effect of angiopoietin-1 upregulation on the outcome of acute ischaemic stroke in rodent models: A meta-analysis.

Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood-brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: -3.02; 95% confidence intervals: -4.41, -1.63; p < 0.001; n = 171 animals) and improved blood-brain barrier integrity (standardized mean difference: -2.02; 95% confidence intervals: -3.27, -0.77; p = 0.002; n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood-brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.