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BACKGROUND: Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing difficulties (FeSS Protocols) in 19 Australian stroke units resulted in reduced death and dependency for stroke patients. However, a significant gap remains in translating this evidence-based care bundle protocol into standard practice in Australia and New Zealand. Facilitation is a key component for increasing implementation. However, its contribution to evidence translation initiatives requires further investigation. We aim to evaluate two levels of intensity of external remote facilitation as part of a multifaceted intervention to improve FeSS Protocol uptake and quality of care for patients with stroke in Australian and New Zealand acute care hospitals. METHODS: A three-arm cluster randomised controlled trial with a process evaluation and economic evaluation. Australian and New Zealand hospitals with a stroke unit or service will be recruited and randomised in blocks of five to one of the three study arms-high- or low-intensity external remote facilitation or a no facilitation control group-in a 2:2:1 ratio. The multicomponent implementation strategy will incorporate implementation science frameworks (Theoretical Domains Framework, Capability, Opportunity, Motivation - Behaviour Model and the Consolidated Framework for Implementation Research) and include an online education package, audit and feedback reports, local clinical champions, barrier and enabler assessments, action plans, reminders and external remote facilitation. The primary outcome is implementation effectiveness using a composite measure comprising six monitoring and treatment elements of the FeSS Protocols. Secondary outcome measures are as follows: composite outcome of adherence to each of the combined monitoring and treatment elements for (i) fever (n=5); (ii) hyperglycaemia (n=6); and (iii) swallowing protocols (n=7); adherence to the individual elements that make up each

Introduction: Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing (FeSS) following stroke significantly reduces 90-day death and disability. We present results on FeSS protocol uptake in multiple European countries, including low-and-middle income countries, following implementation facilitation arising from our international collaboration with the European Stroke Organisation, Angels Initiative, and Registry of Stroke Care Quality. Method(s): Our multi-country, multi-centre, pre-test/post-test study was conducted between 2017- 2021. Data were provided at baseline and three months after FeSS protocol implementation. Nursing clinical champions, with support from the Project team (European Liaison Officer, Angels Consultants, Country Coordinators and the Nursing Research Institute) conducted multidisciplinary workshops to examine baseline results, identify barriers and facilitators to protocol implementation, and held education sessions. Outcomes were adjusted for clustering by country and hospital controlling for age/ sex/NIHSS. Result(s): Data from 76 hospitals (18 countries) were received for 3999 patients at baseline, and from 64 hospitals (17 countries) for 3257 patients post-implementation (Total n=7256). Significantly increased proportion of patients received care from pre to post according to the: fever protocol (Pre: 16%, Post: 51%, p<0.0001): hyperglycaemic protocol (Pre: 16%, Post: 52%, p<0.0001): swallow protocol (Pre: 41%, Post: 67%, p<0.0001); and the FeSS Protocols overall (Pre: 3.2%, Post: 35%, p<0.0001). Significant improvements were also found in low-and-middle income countries. Conclusion(s): Facilitated implementation of nurse-initiated FeSS protocols demonstrated successful large-scale translation of evidence into countries with different health care systems, many of which with no access to reperfusion therapies-a European first. This will reduce death and disability post-stroke.

Background and aims: QASC Europe was a collaboration between academics, the European Stroke Organisation and the Angels Initiative. A before-after study evaluated the effect of nurse-led implementation of evidence-based stroke protocols on patient care in 64 European hospitals from 17 countries. A qualitative process evaluation sought to identify factors that influenced protocol implementation from multiple stakeholders' perspectives. Method(s): Focus groups and individual face-to-face videoconference interviews using a semi-structured interview guide. Purposive sampling to recruit interviewees from four stakeholder groups: 1) high-level project governance (senior project team and steering committee members); 2) Angels team leaders; 3) Angels consultants and 4) Stroke Nurse Country Co-ordinators. Interview transcripts were thematically analysed. Result(s): All 22 approached, consented and participated. Participant numbers: n=13 interviews (groups 1 and 2); n=9 across three focus groups (groups 3 and 4). Four themes represent factors that influenced protocol implementation: 1) negotiating expectations; 2) role clarity; 3) optimal communication and 4) ability to tailor and adapt processes. These themes underpin a cascading facilitation model that reflects the sequence of processes and support required for multi-country nurse-led protocol implementation. Stakeholders reported the following benefits: expanded skillsets in implementation science and clinical quality monitoring; nurse leadership in evidence translation; and progressing of national stroke nurse networks. Conclusion(s): A multi-layered collaborative partnership model of cascading facilitation enabled European stroke nurses to develop capability in leading and negotiating practice change at the hospital level. This model has potential for future international scale-up of other evidence translation initiatives.

Background and aim: The QASC Europe project significantly improved nurse-initiated management of fever, hyperglycaemia (sugar) and swallowing (FeSS) in European stroke units with vastly different health care systems. We examined pre-post country management using the 2021-2022 World Bank income classifications. Method(s): This pan-European pre-test/post-test study (2018-2021) collected data at baseline and three months after FeSS protocol implementation. Clinical champions conducted multidisciplinary workshops to feedback baseline audit data, provided education, and identified barriers to protocol implementation. Outcomes were adjusted for age, sex, NIHSS and for clustering by site and country. The interaction between country classification (high income countries [HIC] vs middle income countries [MIC]) and time (pre/post) tested differences in proportions. Result(s): Pre-implementation data were analysed from 76 hospitals in 18 countries (eight HIC, ten MIC) (n=3999 patients); and post-implementation from 64 hospitals in 17 countries (seven HIC and the same ten MIC) (3257 patients). Significant pre-to-post improvements were made in both HIC and MIC (Adjusted difference in proportion HIC:(24% (16%,33%), MIC:(25% (15%,34%)). Post-implementation FeSS Protocol adherence were broadly similar between HIC and MIC. There was no difference in post-implementation overall FeSS Protocol adherence between HIC and MIC (p=0.8909). Conclusion(s): Our nurse-initiated intervention was highly effective in improving stroke management in all countries irrespective of their income level classification. The clinical significance of these improvements in MIC is noteworthy in that many of these hospitals have limited access to stroke care including acute reperfusion therapies. Upscaling of effective stroke interventions is essential to improving stroke care globally.

Background: The QASC Europe project is an international collaboration between the Nursing Research Institute (NRI); Australian Catholic University; European Stroke Organisation and Angels Initiative. The project evaluated implementation of nurse-initiated protocols for Fever, hyperglycaemia (Sugar) and Swallowing (FeSS) into stroke units in 64 European countries. Aim(s): A qualitative process evaluation was conducted to understand barriers and facilitators to nurseled protocol implementation from the viewpoint of stakeholders who were involved in promotion of protocol uptake. Method(s): Focus groups and individual face-to-face videoconference interviews were audiotaped. Purposive sampling was used to recruit: i) high-level project governance representatives (clinicians, researchers; industry executives); ii) Angels Initiative team leaders; iii) Angels Initiative consultants and iv) senior stroke nurse country co-ordinators. Transcripts were thematically analysed and mapped to barriers and facilitators. Result(s): Participant numbers were: n=12 interviews and n=5 in each of two focus groups. Barriers and facilitators that influenced facilitation were mapped to five themes: 1) negotiating expectations; 2) roles and responsibilities; 3) readiness for change; 4) communication systems and 5) tailoring and adapting implementation processes. Conclusion(s): A shared goal across stakeholders of improved stroke care was an overarching enabler to the implementation process. Barriers were: commencing the implementation process prior to the establishment of an agreed communication system, system readiness and uncertainty about some roles and responsibilities. Despite differences in perspectives and foci, implementing evidence-based clinical change within hospitals can be initiated outside of the healthcare system and facilitated by academic-industry partnerships.

Background and Aim: Assisted implementation of FeSS protocols following stroke significantly reduces 90-day death and disability and longer-term mortality. The QASC Europe project, a novel international collaboration between: Nursing Research Institute (NRI); European Stroke Organisation; Angels Initiative; and Registry of Stroke Care Quality (RES-Q) facilitated implementation of nurseinitiated Fever, hyperglycaemia (Sugar) and Swallowing (FeSS) protocols into stroke units across Europe. Method(s): A multi-country, multi-centre pre-test/post-test study was conducted (2017-2021). Baseline and post-implementation data (3-months after FeSS protocol introduction) were entered into RES-Q. Nursing clinical champions, with support from the Project team (European Liaison Officer, Angels Consultants, Country Coordinators and the NRI) conducted multidisciplinary workshops identifying barriers and facilitators to protocol implementation and held education sessions. Outcomes were adjusted for clustering by country and hospital controlling for age/sex/NIHSS. Result(s): At baseline, 76 hospitals in 18 countries (n=4196 patients); and post-implementation, 64 hospitals in 17 countries (3348 patients) participated (Total n=7544). There were improvements in: temperature monitoring on day of admission (Pre: 43%; Post: 79%, p<0.00001); treatment of fever >37.5degreeC with paracetamol within one hour (Pre: 57%; Post: 79%, p<0.00001); blood glucose monitoring on day of admission (Pre: 38%; Post: 75%, p<0.00001); treatment of hyperglycemia >10mmol/L with insulin within one hour (Pre: 59%; Post: 75%, p<0.00001); and swallow screening before food or fluids (Pre: 59%; Post: 83%, p<0.00001). Conclusion(s): This international collaboration has enabled the success of large-scale implementation of FeSS protocols into countries with vastly different health care systems. Similar partnerships should be considered for future translation of effective stroke interventions to reach a greater proportion

Background and Aims: The QASC Europe project significantly improved nurse-initiated management of: fever, hyperglycaemia (sugar) and swallowing (FeSS) in European stroke units with varying health care systems. We examined pre-post management for low-and-middle-income-countries (LMIC). Method(s): Data from this multi-site, multi-country, pre-test/post-test study (2018-2021) were collected at baseline and three months after FeSS protocol implementation. Clinical champions conducted multidisciplinary workshops to feedback baseline audit data results, provided education, and identified barriers to protocol implementation. Outcomes were adjusted for age, sex, NIHSS, country and within clustering by site. Result(s): Data were received from 76 hospitals in 18 countries (n=4196 patients); and post-implementation, 64 hospitals in 17 countries (3348 patients). 13 hospitals (pre-implementation, n=648 patients) and 9 hospital (post-implementation, n=444 patients) from six LMIC Significant improvements were achieved from pre-to-post implementation in LMIC for: monitoring of temperature at least four times on day three (26% vs 62%, p=0.018); venous blood glucose level (BLG) on admission (86% vs 98%, p=0.0256); BGL monitored four times/day on day of admission to stroke unit (51% vs 84%, p=0.001); swallow screen/assessment performed before oral medication (73% vs 94%, p=0.039); and swallow screen/assessment before being given oral food or fluid (76% vs 93%, p=0.007). Results from LMIC were broadly consistent with those from high-income countries. Conclusion(s): Our nurse-initiated intervention was highly effective in improving stroke outcomes in LMIC. While LMIC are known to have reduced thrombolysis rates, that they are providing comparable evidenced-based care for fever, hyperglycaemia and swallowing is noteworthy. Upscaling of effective stroke interventions is essential to improving stroke outcomes globally.

Background and Aims: The Quality in Acute Stroke (QASC) trial demonstrated a significant reduction in death and disability when clinicians were assisted to introduce protocols to manage fever, hyperglycaemia (sugar) and swallowing (FeSS) following stroke. A unique international collaboration between the Nursing Research Institute, Australian Catholic University; the European Stroke Organisation; and the Angels Initiative is underway to implement the FeSS Protocols into 20 European countries. We present baseline (pre-FeSS implementation) results for management of these important physiological parameters post-stroke Methods: Data were entered into the European Registry of Stroke Care Quality (RES-Q) for 7 indicators of FeSS care between 2017-2019. Result(s): Forty hospitals from 13 countries completed baseline data entry (n=2266 patients). Paracetamol was administered within one hour following temperature >37.5degreeC C for 58% of patients (n=214/367). When glucose was >10mmols/L, 60% of patients (n=241/403) received insulin within one hour. 57% of patients (1293/2266) received a swallow screen or assessment before being given oral food, fluids or medications. Conclusion(s): All FeSS processes of care need improving, and we are actively working with the Angels Initiative and clinicians to implement the FeSS protocols which have been translated into 13 different languages. Successful large-scale implementation of these evidence-based, nurse-initiated protocols into countries with vastly different health care systems, many of whom also have no access to reperfusion therapies, is likely to make a significant impact on reducing death and disability after stroke.

Amyotrophic lateral sclerosis (ALS) presents a poorly understood pathogenesis. Evidence from patients and mutant SOD1 mouse models suggests vascular damage may precede or aggravate motor dysfunction in ALS. We have previously shown angiogenin (ANG) treatment enhances motor neuron survival, delays motor dysfunction and prevents vascular regression in the SOD1G93A ALS model. However, the existence of vascular defects at different stages of disease progression remains to be established in other ALS models. Here, we assessed vascular integrity in vivo throughout different disease stages, and investigated whether ANG treatment reverses vascular regression and prolongs motor neuron survival in the FUS (1-359) mouse model of ALS. Lumbar spinal cord tissue was collected from FUS (1-359) and non-transgenic control mice at postnatal day (P)50, P90 and P120. We found a significant decrease in vascular network density in lumbar spinal cords from FUS (1-359) mice by day 90, at which point motor neuron numbers were unaffected. ANG treatment did not affect survival or counter vascular regression. Endogenous Ang1 and Vegf expression were unchanged at P50 and P90; however, we found a significant decrease in miRNA 126 at P50, indicating vascular integrity in FUS mice may be compromised via an alternative pathway. Our study demonstrates that vascular regression occurs before motor neuron degeneration in FUS (1-359) mice, and highlights that heterogeneity in responses to novel ALS therapeutics can already be detected in preclinical mouse models of ALS., QC 20191030

Emergency medical services (EMS) are vital to ensuring acute stroke patients are transported to thrombolysis and/or stroke unit centres. This 6-month audit of Victorian EMS cases found the majority of suspected acute strokes are transported to appropriate stroke centres. However, there is still room for improvement, in particular, strategies to improve access to stroke services in some rural regions and to ensure patients/relatives are fully informed when requesting transport to a non-stroke service hospital.

Background and purpose: Recent evidence suggests the Cincinnati Prehospital Stroke Scale is ineffectively used and lacks sensitivity and specificity. Melbourne (Australia) paramedics have been using the Melbourne Ambulance Stroke Screen (MASS) since 2005. The aim of this study was to review the real-world use of MASS 3 years after citywide implementation. Methods: Two groups of consecutively admitted patients to an Australian hospital between January and May 2008 were used: (1) patients for whom paramedics performed MASS; and (2) patients with a discharge diagnosis of stroke or transient ischemic attack. Use of MASS was examined for all transports and for patients diagnosed with stroke or transient ischemic attack. The sensitivity and specificity of paramedic diagnosis, MASS, and Cincinnati Prehospital Stroke Scale were calculated. Paramedic diagnosis of stroke among patients with stroke was statistically compared with those obtained immediately post-MASS implementation in 2002. Results: For the study period, MASS was performed for 850 (16%) of 5286 emergency transports, including 199 of 207 (96%) patients with confirmed stroke and transient ischemic attack. In patients in whom MASS was performed (n=850), the sensitivity of paramedic diagnosis of stroke (93%, 95% CI: 88% to 96%) was higher than the MASS (83%, 95% CI: 77% to 88%, P=0.003) and equivalent to Cincinnati Prehospital Stroke Scale (88%, 95% CI: 83% to 92%, P=0.120), whereas the specificity of the paramedic diagnosis of stroke (87%, 95% CI: 84% to 89%) was equivalent to MASS (86%, 95% CI: 83% to 88%, P=0.687) and higher than Cincinnati Prehospital Stroke Scale (79%, 95% CI: 75% to 82%, P<0.001). The initial improvement in stroke paramedic diagnosis seen in 2002 (94%, 95% CI: 86% to 98%) was sustained in 2008 (89%, 95% CI: 84% to 94%, P=0.19). Conclusion: In our experience, paramedics have successfully incorporated MASS into the assessment of neurologically compromised patients. The initial improvement to