Sustaining a New Model of Acute Stroke Care: A Mixed-Method Process Evaluation of the Melbourne Mobile Stroke Unit.

BACKGROUND: Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. METHODS: Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. RESULTS: There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (ß=0.61), not experiencing pressure/tension about working on the MSU (ß=0.17) and thinking they did well working within the team model (ß=0.17) were significantly associated with wanting to continue working within the MSU model [R2=0.76; F(15, 60)=12.76, P<.001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. CONCLUSION: Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability.

Cost-effectiveness of tenecteplase versus alteplase for stroke thrombolysis evaluation trial in the ambulance.

BACKGROUND: Tenecteplase administered to patients with ischaemic stroke in a mobile stroke unit (MSU) has been shown to reduce the perfusion lesion volumes and result in ultra-early recovery. We now seek to assess the cost-effectiveness of tenecteplase in the MSU. METHODS: A within-trial (TASTE-A) economic analysis and a model-based long-term cost-effectiveness analysis were performed. This post hoc within-trial economic analysis utilised the patient-level data (intention to treat, ITT) prospectively collected over the trial to calculate the difference in both healthcare costs and quality-adjusted life years (QALYs, estimated from modified Rankin scale score). A Markov microsimulation model was developed to simulate the long-term costs and benefits. RESULTS: In total, there were 104 patients with ischaemic stroke randomised to tenecteplase (n = 55) or alteplase (n = 49) treatment groups, respectively in the TASTE-A trial. The ITT-based analysis showed that treatment with tenecteplase was associated with non-signficantly lower costs (A$28,903 vs A$40,150 (p = 0.056)) and greater benefits (0.171 vs 0.158 (p = 0.457)) than that for the alteplase group over the first 90 days post the index stroke. The long-term model showed that tenecteplase led to greater savings in costs (-A$18,610) and more health benefits (0.47 QALY or 0.31 LY gains). Tenecteplase-treated patients had reduced costs for rehospitalisation (-A$1464), nursing home care (-A$16,767) and nonmedical care (-A$620) per patient. CONCLUSIONS: Treatment of ischaemic stroke patients with tenecteplase appeared to be cost-effective and improve QALYs in the MSU setting based on Phase II data. The reduced total cost from tenecteplase was driven by savings from acute hospitalisation and reduce need for nursing home care.

Interdisciplinary interactions, social systems and technical infrastructure required for successful implementation of mobile stroke units: A qualitative process evaluation.

RATIONALE: Mobile stroke units (MSUs) are increasingly being implemented to provide acute stroke care in the prehospital environment, but a comprehensive implementation evaluation has not been undertaken. AIM: To identify successes and challenges in the pre- and initial operations of the first Australian MSU service from an interdisciplinary perspective. METHODS: Process evaluation of the Melbourne MSU with a mixed-methods design. Purposive sampling targeted key stakeholder groups. Online surveys (administered June-September 2019) and semistructured interviews (October-November 2019) explored experiences. Directed content analysis (raters' agreement 85%) and thematic analysis results are presented using the Interactive Sociotechnical Analysis framework. RESULTS: Participants representing executive/program operations, MSU clinicians and hospital-based clinicians completed 135 surveys and 38 interviews. Results converged, with major themes addressing successes and challenges: stakeholders, vehicle, knowledge, training/education, communication, work processes and working relationships. CONCLUSIONS: Successes and challenges of establishing a new MSU service extend beyond technical, to include operational and social aspects across prehospital and hospital environments.

Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomised, open-label trial.

BACKGROUND: Mobile stroke units (MSUs) equipped with a CT scanner reduce time to thrombolytic treatment and improve patient outcomes. We tested the hypothesis that tenecteplase administered in an MSU would result in superior reperfusion at hospital arrival, when compared with alteplase. METHODS: The TASTE-A trial is a phase 2, randomised, open-label trial at the Melbourne MSU and five tertiary hospitals in Melbourne, VIC, Australia. Patients (aged ≥18 years) with ischaemic stroke who were eligible for thrombolytic treatment were randomly allocated in the MSU to receive, within 4·5 h of symptom onset, either standard-of-care alteplase (0·9 mg/kg [maximum 90 mg], administered intravenously with 10% as a bolus over 1 min and 90% as an infusion over 1 h), or the investigational product tenecteplase (0·25 mg/kg [maximum 25 mg], administered as an intravenous bolus over 10 s), before being transported to hospital for ongoing care. The primary outcome was the volume of the perfusion lesion on arrival at hospital, assessed by CT-perfusion imaging. Secondary safety outcomes were modified Rankin Scale (mRS) score of 5 or 6 at 90 days, symptomatic intracerebral haemorrhage and any haemorrhage within 36 h, and death at 90 days. Assessors were masked to treatment allocation. Analysis was by intention-to-treat. The trial was registered with ClinicalTrials.gov, NCT04071613, and is completed. FINDINGS: Between June 20, 2019, and Nov 16, 2021, 104 patients were enrolled and randomly allocated to receive either tenecteplase (n=55) or alteplase (n=49). The median age of patients was 73 years (IQR 61-83), and the median NIHSS at baseline was 8 (5-14). On arrival at the hospital, the perfusion lesion volume was significantly smaller with tenecteplase (median 12 mL [IQR 3-28]) than with alteplase (35 mL [18-76]; adjusted incidence rate ratio 0·55, 95% CI 0·37-0·81; p=0·0030). At 90 days, an mRS of 5 or 6 was reported in eight (15%) patients allocated to tenecteplase and ten (20%) patients allocated to alteplase (adjusted odds ratio [aOR] 0·70, 95% CI 0·23-2·16; p=0·54). Five (9%) patients allocated to tenecteplase and five (10%) patients allocated to alteplase died from any cause at 90 days (aOR 1·12, 95% CI 0·26-4·90; p=0·88). No cases of symptomatic intracerebral haemorrhage were reported within 36 h with either treatment. Up to day 90, 13 serious adverse events were noted: five (5%) in patients treated with tenecteplase, and eight (8%) in patients treated with alteplase. INTERPRETATION: Treatment with tenecteplase on the MSU in Melbourne resulted in a superior rate of early reperfusion compared with alteplase, and no safety concerns were noted. This trial provides evidence to support the use of tenecteplase and MSUs in an optimal model of stroke care. FUNDING: Melbourne Academic Centre for Health.

The Mobile Stroke Unit Nurse: An International Exploration of Their Scope of Practice, Education, and Training.

ABSTRACT: BACKGROUND: Mobile stroke units (MSUs) are ambulance-based prehospital stroke care services. Through immediate roadside assessment and onboard brain imaging, MSUs provide faster stroke management with improved patient outcomes. Mobile stroke units have enabled the development of expanded scope of practice for stroke nurses; however, there is limited published evidence about these evolving prehospital acute nursing roles. AIMS: The aim of this study was to explore the expanded scope of practice of nurses working on MSUs by identifying MSUs with onboard nurses; describing the roles and responsibilities, training, and experience of MSU nurses, through a search of the literature; and describing 2 international MSU services incorporating nurses from Memphis, Tennessee, and Melbourne, Australia. METHODS: We searched PubMed, CINAHL, and the Joanna Briggs Institute Evidence-Based Practice database using the terms "mobile stroke unit" and "nurse." Existing MSUs were identified through the PRE-hospital Stroke Treatment Organization to determine models that involved nurses. We describe 2 MSUs involving nurses: one in Memphis and one in Melbourne, led by 2 of our authors. RESULTS: Ninety articles were found describing 15 MSUs; however, staffing details were lacking, and it is unknown how many employ nurses. Nine articles described the role of the nurse, but role specifics, training, and expertise were largely undocumented. The MSU in Memphis, the only unit to be staffed exclusively by onboard nurse practitioners, is supported by a neurologist who consults via telephone. The Melbourne MSU plans to trial a nurse-led telemedicine model in the near future. CONCLUSION: We lack information on how many MSUs employ nurses, and the nurses' scope of practice, training, and expertise. Expert stroke nurse practitioners can safely perform many of the tasks undertaken by the onboard neurologist, making a nurse-led telemedicine model an effective and potentially cost-effective model that should be considered for all MSUs.

Mobile Stroke Units Facilitate Prehospital Management of Intracerebral Hemorrhage.

Background and Purpose: Mobile stroke units (MSUs) improve reperfusion therapy times in acute ischemic stroke (AIS). However, prehospital management options for intracerebral hemorrhage (ICH) are less established. We describe the initial Melbourne MSU experience in ICH. Methods: Consecutive patients with ICH and AIS treated by the Melbourne MSU were included. We describe demographics, proportions of patients receiving specific therapies, and bypass to comprehensive/neurosurgical centers. We also compare operational time metrics between patients with MSU-ICH and MSU-AIS. Results: During a 2-year period, the Melbourne MSU managed 49 patients with ICH, mean (SD) age 74 (12) years, median (interquartile range) National Institutes of Health Stroke Scale 17 (12­20). Intravenous antihypertensives were the commonest treatment provided (46.9%). Bypass of a primary center to a comprehensive center with neurosurgical expertise occurred in 32.7% of patients with MSU-ICH compared with 20.5% of patients with MSU-AIS. Compared with patients with MSU-AIS, patients with MSU-ICH had faster onset-to-emergency-call, and onset-to-scene-arrival times at the median and 75th percentiles. Conclusions: MSUs can facilitate ultra-early ICH diagnosis, management, and triage.

Economic evaluation of the Melbourne Mobile Stroke Unit.

BACKGROUND: The Melbourne Mobile Stroke Unit (MSU) is the first Australian service to provide prehospital acute stroke treatment, including thrombolysis and facilitated triage for endovascular thrombectomy. AIMS: To estimate the cost-effectiveness of the MSU during the first full year of operation compared with standard ambulance and hospital stroke care pathways (standard care). METHODS: The costs and benefits of the Melbourne MSU were estimated using an economic simulation model. Operational costs and service utilization data were obtained from the MSU financial and patient tracking reports. The health benefits were estimated as disability-adjusted life years (DALYs) avoided using local data on reperfusion therapy and estimates from the published literature on their effectiveness. Costs were presented in Australian dollars. The robustness of results was assessed using multivariable (model inputs varied simultaneously: 10,000 Monte Carlo iterations) and various one-way sensitivity analyses. RESULTS: In 2018, the MSU was dispatched to 1244 patients during 200 days of operation. Overall, 167 patients were diagnosed with acute ischemic stroke, and 58 received thrombolysis, endovascular thrombectomy, or both. We estimated 27.94 DALYs avoided with earlier access to endovascular thrombectomy (95% confidence interval (CI) 15.30 to 35.93) and 16.90 DALYs avoided with improvements in access to thrombolysis (95% CI 9.05 to 24.68). The MSU was estimated to cost an additional $30,982 per DALY avoided (95% CI $21,142 to $47,517) compared to standard care. CONCLUSIONS: There is evidence that the introduction of MSU is cost-effective when compared with standard care due to earlier provision of reperfusion therapies.

Aeromedical Retrieval for Stroke in Australia.

INTRODUCTION: Rural, remote, and Indigenous stroke patients have worse stroke outcomes than urban Australians. This may be due to lack of timely access to expert facilities. OBJECTIVES: We aimed to describe the characteristics of patients who underwent aeromedical retrieval for stroke, estimate transfer times, and investigate if flight paths corresponded with the locations of stroke units (SUs) throughout Australia. METHODS: Prospective review of routinely collected Royal Flying Doctor Service (RFDS) data. Patients who underwent an RFDS aeromedical retrieval for stroke, July 2014-June 2018 (ICD-10 codes: I60-I69), were included. To define the locations of SUs throughout Australia, we accessed data from the 2017 National Stroke Audit. The main outcome measures included determining the characteristics of patients with an in-flight diagnosis of stroke, their subsequent pickup and transfer locations, and corresponding SU and imaging capacity. RESULTS: The RFDS conducted 1,773 stroke aeromedical retrievals, consisting of 1,028 (58%) male and 1,481 (83.5%) non-Indigenous and 292 (16.5%) Indigenous patients. Indigenous patients were a decade younger, 56.0 (interquartile range [IQR] 45.0-64.0), than non-Indigenous patients, 66.0 (IQR 54.0-76.0). The most common diagnosis was "stroke not specified," reflecting retrieval locations without imaging capability. The estimated median time for aeromedical retrieval was 238 min (95% confidence interval: 231-244). Patients were more likely to be transferred to an area with SU and imaging capability (both p < 0.0001). CONCLUSION: Stroke patients living in rural areas were younger than those living in major cities (75 years, Stroke Audit Data), with aeromedically retrieved Indigenous patients being a decade younger than non-Indigenous patients. The current transfer times are largely outside the time windows for reperfusion methods. Future research should aim to facilitate more timely diagnosis and treatment of stroke.

Melbourne Mobile Stroke Unit and Reperfusion Therapy: Greater Clinical Impact of Thrombectomy Than Thrombolysis.

Background and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU. Methods- Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates. Results- In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes (P<0.001) for dispatch to hospital arrival and 15 minutes (P<0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0-49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes ([95% CI, 30.1-71.9], P<0.001). This included a median time saving of 17 minutes ([95% CI, 7.6-26.4], P=0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT. Conclusions- The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.

Prehospital idarucizumab prior to intravenous thrombolysis in a mobile stroke unit.

BACKGROUND: Administration of intravenous idarucizumab to reverse dabigatran anticoagulation prior to thrombolysis for patients with acute ischemic stroke has been previously described, but not in the prehospital setting. The speed and predictability of idarucizumab reversal is well suited to prehospital treatment in a mobile stroke unit and allows patients with recent dabigatran intake to access reperfusion therapy. AIMS: To describe feasibility of prehospital idarucizumab administration prior to thrombolysis on the Melbourne mobile stroke unit. METHODS: The Melbourne mobile stroke unit is a specialized stroke ambulance servicing central metropolitan Melbourne, Australia and provides prehospital assessment, scanning and treatment with an integrated CT scanner and multidisciplinary stroke team. All cases were identified through the mobile stroke unit treatment registry since launch in November 2017. RESULTS: Of a total of n = 20 thrombolysis cases in the first 4 months of operation, three patients (15%) received intravenous idarucizumab 5 g for dabigatran reversal prior to thrombolysis. Mean time between idarucizumab administration and thrombolysis was approximately 10 minutes. Two of the three patients were shown to have large vessel occlusion on CTA in the mobile stroke unit and proceeded to endovascular thrombectomy. At 24 hours, only one patient had a small amount of asymptomatic petechial hemorrhage on follow-up imaging. All patients demonstrated substantial neurological recovery and were discharged to inpatient rehabilitation. CONCLUSIONS: Rapid treatment with prehospital administration of idarucizumab prior to thrombolysis using a mobile stroke unit is feasible and facilitates hyperacute treatment.

Air-Mobile Stroke Unit for access to stroke treatment in rural regions.

Background In recent years, important progress has been made in effective stroke treatment, however, patients living in rural and remote areas have nil or very limited access to timely reperfusion therapies. Aims Novel systems of care to overcome the detrimental treatment gap for stroke patients living in rural and remote regions need to be developed. Summary of review A possible solution to the treatment disparity between stroke patients living in metropolitan and rural areas may involve the use of specially designed aircrafts equipped with the ability to diagnose and treat acute stroke at remote emergency sites. We describe technical solutions for an Air-Mobile Stroke Unit (Air-MSU) concept, where an aircraft is customized with the ability to perform multimodal computed tomography, in addition to onboard laboratory equipment and telemedicine connection. The Air-MSU is envisioned not only to allow intravenous thrombolysis in the field but also to allow prehospital triage to a comprehensive stroke center through use of contrast intracerebral vascular imaging. Several options for the Air-MSU approach are described, and issues regarding the potential medical benefit, optimal operating environment, technical realization, and integration in pre-existing solutions (e.g., flying doctor service) are addressed. Conclusion The Air-MSU may represent a novel tool to reduce treatment disparity for stroke patients in rural and remote areas. However, this approach requires further implementation research to determine the overall benefit to these communities.

Roles of ligands from the TNF superfamily in B cell development, function, and regulation.

Most ligands from the tumour necrosis factor (TNF) superfamily play very important roles in the immune system, and particularly so in B lymphocyte biology. TNF ligands are essential to many aspects of normal B cell biology from development in the bone marrow to maturation in the periphery as well as for activation and differentiation into germinal centre, memory or plasma cells. TNF ligands also influence other aspects of B cell biology such as their ability to present antigens or regulate immune responses. Importantly, inadequate regulation of many TNF ligands is associated with B cell disorders including autoimmunity and cancers. As a result, inhibitors of a number of TNF ligands have been tested in the clinic, with some becoming very successful approved treatments alleviating B cell-mediated pathologies.

The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.

The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials.