Tenecteplase real-world data: A three phase sequential comparison.

INTRODUCTION: The New Zealand (NZ) Central Region Stroke Network, serving 1.17 million catchment population, changed to tenecteplase for stroke thrombolysis in 2020 but was forced to revert to Alteplase in 2021 due to a sudden cessation of drug supply. We used this unique opportunity to assess for potential before and after temporal trend confounding. PATIENTS AND METHODS: In NZ all reperfused patients are entered prospectively into a national database for safety monitoring. We assessed Central Region patient outcomes and treatment metrics over three time periods: alteplase use (January 2018-January 2020); during switch to tenecteplase (February 2020-February 2021) and after reverting to alteplase (February 2021-December 2022) adjusting regression analyses for hospital, age, onset-to-needle, NIHSS, pre-morbid mRS and thrombectomy. RESULTS: Between January 2018 and December 2022, we treated 1121 patients with Alteplase and 286 with tenecteplase. Overall, patients treated with tenecteplase had greater odds of favorable outcome ordinal mRS [aOR = 1.43 (95% CI = 1.11-1.85)]; shorter door-to-needle (DTN) time [median 52 (IQR 47-83) vs 61 (45-84) minutes, p < 0.0001] and needle to groin (NTG) times [118 (74.5-218.5) vs 185 (118-255); p = 0.02)]. Symptomatic intracerebral hemorrhage (sICH) rate was lower in tenecteplase group [aOR 0.29 (0.09-0.95)]. Findings similarly favored tenecteplase when comparing tenecteplase to only the second alteplase phase. There was no inter-group difference when comparing the two alteplase phases. CONCLUSIONS: Our results suggest that previously reported benefits from tenecteplase in a real-world setting were not likely attributable to a temporal confounding.

Ethnic differences in stroke outcomes in Aotearoa New Zealand: A national linkage study.

BACKGROUND: Ethnic differences in post-stroke outcomes have been largely attributed to biological and socioeconomic characteristics resulting in differential risk factor profiles and stroke subtypes, but evidence is mixed. AIMS: This study assessed ethnic differences in stroke outcome and service access in New Zealand (NZ) and explored underlying causes in addition to traditional risk factors. METHODS: This national cohort study used routinely collected health and social data to compare post-stroke outcomes between NZ Europeans, Maori, Pacific Peoples, and Asians, adjusting for differences in baseline characteristics, socioeconomic deprivation, and stroke characteristics. First and principal stroke public hospital admissions during November 2017 to October 2018 were included (N = 6879). Post-stroke unfavorable outcome was defined as being dead, changing residence, or becoming unemployed. RESULTS: In total, 5394 NZ Europeans, 762 Maori, 369 Pacific Peoples, and 354 Asians experienced a stroke during the study period. Median age was 65 years for Maori and Pacific Peoples, and 71 and 79 years for Asians and NZ Europeans, respectively. Compared with NZ Europeans, Maori were more likely to have an unfavorable outcome at all three time-points (odds ratio (OR) = 1.6 (95% confidence interval (CI) = 1.3-1.9); 1.4 (1.2-1.7); 1.4 (1.2-1.7), respectively). Maori had increased odds of death at all time-points (1.7 (1.3-2.1); 1.5 (1.2-1.9); 1.7 (1.3-2.1)), change in residence at 3 and 6 months (1.6 (1.3-2.1); 1.3 (1.1-1.7)), and unemployment at 6 and 12 months (1.5 (1.1-2.1); 1.5 (1.1-2.1)). There was evidence of differences in post-stroke secondary prevention medication by ethnicity. CONCLUSION: We found ethnic disparities in care and outcomes following stroke which were independent of traditional risk factors, suggesting they may be attributable to stroke service delivery rather than patient factors.

Comparison of Stroke Care Costs in Urban and Nonurban Hospitals and Its Association With Outcomes in New Zealand: A Nationwide Economic Evaluation.

BACKGROUND: Although geographical differences in treatment and outcomes after stroke have been described, we lack evidence on differences in the costs of treatment between urban and nonurban regions. Additionally, it is unclear whether greater costs in one setting are justified given the outcomes achieved. We aimed to compare costs and quality-adjusted life years in people with stroke admitted to urban and nonurban hospitals in New Zealand. METHODS: Observational study of patients with stroke admitted to the 28 New Zealand acute stroke hospitals (10 in urban areas) recruited between May and October 2018. Data were collected up to 12 months poststroke including treatments in hospital, inpatient rehabilitation, other health service utilization, aged residential care, productivity, and health-related quality of life. Costs in New Zealand dollars were estimated from a societal perspective and assigned to the initial hospital that patients presented to. Unit prices for 2018 were obtained from government and hospital sources. Multivariable regression analyses were conducted when assessing differences between groups. RESULTS: Of 1510 patients (median age 78 years, 48% female), 607 presented to nonurban and 903 to urban hospitals. Mean hospital costs were greater in urban than nonurban hospitals ($13 191 versus $11 635, P=0.002), as were total costs to 12 months ($22 381 versus $17 217, P<0.001) and quality-adjusted life years to 12 months (0.54 versus 0.46, P<0.001). Differences in costs and quality-adjusted life years remained between groups after adjustment. Depending on the covariates included, costs per additional quality-adjusted life year in the urban hospitals compared to the nonurban hospitals ranged from $65 038 (unadjusted) to $136 125 (covariates: age, sex, prestroke disability, stroke type, severity, and ethnicity). CONCLUSIONS: Better outcomes following initial presentation to urban hospitals were associated with greater costs compared to nonurban hospitals. These findings may inform greater targeted expenditure in some nonurban hospitals to improve access to treatment and optimize outcomes.

Patient, carer and health worker perspectives of stroke care in New Zealand: a mixed methods survey.

PURPOSE: It is important to understand how consumers (person with stroke/family member/carer) and health workers perceive stroke care services. MATERIALS AND METHODS: Consumers and health workers from across New Zealand were surveyed on perceptions of stroke care, access barriers, and views on service centralisation. Quantitative data were summarised using descriptive statistics whilst thematic analysis was used for free-text answers. RESULTS: Of 149 consumers and 79 health workers invited to complete a survey, 53 consumers (36.5%) and 41 health workers (51.8%) responded. Overall, 40/46 (87%) consumers rated stroke care as 'good/excellent' compared to 24/41 (58.6%) health workers. Approximately 72% of consumers preferred to transfer to a specialised hospital. We identified three major themes related to perceptions of stroke care: 1) 'variability in care by stage of treatment'; 2) 'impact of communication by health workers on care experience'; and 3) 'inadequate post-acute services for younger patients'. Four access barrier themes were identified: 1) 'geographic inequities'; 2) 'knowing what is available'; 3) 'knowledge about stroke and available services'; and 4) 'healthcare system factors'. CONCLUSIONS: Perceptions of stroke care differed between consumers and health workers, highlighting the importance of involving both in service co-design. Improving communication, post-hospital follow-up, and geographic equity are key areas for improvement.Implications for rehabilitationProvision of detailed information on stroke recovery and available services in the community is recommended.Improvements in the delivery of post-hospital stroke care are required to optimise stroke care, with options including routine phone follow up appointments and wider development of early supported discharge services.Stroke rehabilitation services should continue to be delivered 'close to home' to allow community integration.Telehealth is a likely enabler to allow specialist urban clinicians to support non-urban clinicians, as well as increasing the availability and access of community rehabilitation.

Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

Barriers to optimal stroke service care and solutions: a qualitative study engaging people with stroke and their whanau.

AIM: The aim of this study was to explore the perspectives of people with stroke and their whanau on barriers to accessing best practice care across Aotearoa, and to brainstorm potential solutions. METHOD: We conducted ten focus groups nationwide and completed a thematic analysis. RESULTS: Analysis of the data collected from the focus groups identified five themes: (1) inconsistencies in stroke care; (2) importance of effective communication; (3) the role of whanau support; (4) the need for more person rather than stroke centred processes; and (5) experienced inequities. Participants also identified potential solutions. CONCLUSION: Key recommendations include the need for improved access to stroke unit care for rural residents, improved post-discharge support and care coordination involving the whanau, improved communication across the patient journey, and a concerted effort to improve culturally safe care. Next step is to implement and monitor these recommendations.

Geographic Disparities in Stroke Outcomes and Service Access: A Prospective Observational Study.

BACKGROUND AND OBJECTIVE: International evidence shows that patients treated at non-urban hospitals experience poorer access to key stroke interventions. Evidence whether this results in poorer outcomes is conflicting and generally based on administrative or voluntary registry data. The aim of this study was to use prospective high-quality comprehensive nationwide patient level data to investigate the association between hospital geography and stroke patient outcomes and access to best practice stroke care in New Zealand. METHODS: This is a prospective, multi-centre, nationally representative observational study involving all 28 New Zealand acute stroke hospitals (18 non-urban), and affiliated rehabilitation and community services. Consecutive adults admitted to the hospital with acute stroke between 1 May and 31 October 2018 were captured. Outcomes included functional outcome (modified Rankin Scale (mRS) shift analysis), functional independence (mRS scores 0-2), quality of life (EQ5D-3L), stroke/vascular events, and death at 3, 6, and 12 months and proportion accessing thrombolysis, thrombectomy, stroke units, key investigations, secondary prevention, and inpatient/community rehabilitation. Results were adjusted for age, sex, ethnicity, stroke severity/type, co-morbidities, baseline function, and differences in baseline characteristics. RESULTS: Overall, 2,379 patients were eligible (mean (standard deviation) age 75 (13.7); 51.2% male; 1,430 urban; 949 non-urban). Patients treated at non-urban hospitals were more likely to score in a higher mRS category (greater disability) at three (aOR=1.28, 1.07-1.53), six (aOR=1.33, 1.07-1.65) and twelve months (aOR=1.31, 1.06-1.62) and were more likely to have died (aOR=1.57, 1.17-2.12) or experienced recurrent stroke and vascular events at 12 months (aOR=1.94, 1.14-3.29 and aOR=1.65, 1.09-2.52). Fewer non-urban patients received recommended stroke interventions including endovascular thrombectomy (aOR=0.25, 95% confidence interval 0.13-0.49), acute stroke unit care (aOR=0.60, 0.49-0.73), antiplatelet prescriptions (aOR=0.72, 0.58-0.88), ≥60 minutes daily physical therapy (aOR=0.55, 0.40-0.77) and community rehabilitation (aOR=0.69, 0.56-0.84). DISCUSSION: Patients managed at non-urban hospitals experience poorer stroke outcomes and reduced access to key stroke interventions across the entire care continuum. Efforts to improve access to high quality stroke care in non-urban hospitals should be a priority.

Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial.

BACKGROUND: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. METHODS: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. FINDINGS: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01-2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24-3.79). Other outcomes (disability - Barthel Index, quality of life - EQ-visual analogue scale, cognition - telephone mini-mental state examination, and mood - Zung depression scale) were also worse with continuing treatment. INTERPRETATION: In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse functional outcome, disability, cognition, mood, quality of life and increased death. Future studies assessing continuing or stopping prior antihypertensives in the context of thrombectomy are awaited.

The impact of ethnicity on stroke care access and patient outcomes: a New Zealand nationwide observational study.

BACKGROUND: Ethnic inequities in stroke care access have been reported internationally but the impact on outcomes remains unclear. In New Zealand, data on ethnic stroke inequities and resultant effects on outcomes are generally limited and conflicting. METHODS: In a prospective, nationwide, multi-centre observational study, we recruited consecutive adult patients with confirmed stroke from 28 hospitals between 1 May and 31 October 2018. Patient outcomes: favourable functional outcomes (modified Rankin Scale 0-2); quality of life (EQ-5D-3L); stroke/vascular events; and death at three, six and 12 months. Process measures: access to reperfusion therapies, stroke-units, investigations, secondary prevention, rehabilitation. Multivariate regression analyses assessed associations between ethnicity and outcomes and process measures. FINDINGS: The cohort comprised 2,379 patients (median age 78 (IQR 66-85); 51·2% male; 76·7% European, 11·5% Maori, 4·8% Pacific peoples, 4·8% Asian). Non-Europeans were younger, had more risk factors, had reduced access to acute stroke units (aOR=0·78, 95%CI, 0·60-0·97), and were less likely to receive a swallow screen within 24 hours of arrival (aOR=0·72, 0·53-0·99) or MRI imaging (OR=0·66, 0·52-0·85). Maori were less frequently prescribed anticoagulants (OR=0·68, 0·47-0·98). Pacific peoples received greater risk factor counselling. Fewer non-Europeans had a favourable mRS score at three (aOR=0·67, 0·47-0·96), six (aOR=0·63, 0·40-0·98) and 12 months (aOR=0·56, 0·36-0·88), and more Maori had died by 12 months (aOR=1·76, 1·07-2·89). INTERPRETATION: Non-Europeans, especially Maori, had poorer access to key stroke interventions and experience poorer outcomes. Further optimisation of stroke care targeting high-priority populations are needed to achieve equity. FUNDING: New Zealand Health Research Council (HRC17/037).

Economic analysis of the 'Take Charge' intervention for people following stroke: Results from a randomised trial.

OBJECTIVE: To undertake an economic analysis of the Take Charge intervention as part of the Taking Charge after Stroke (TaCAS) study. DESIGN: An open, parallel-group, randomised trial comparing active and control interventions with blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: The Take Charge intervention, a strengths based, self-directed rehabilitation intervention, in two doses (one or two sessions), and a control intervention (no Take Charge sessions). MEASURES: The cost per quality-adjusted life year (QALY) saved for the period between randomisation (always post hospital discharge) and 12 months following acute stroke. QALYs were calculated from the EuroQol-5D-5L. Costs of stroke-related and non-health care were obtained by questionnaire, hospital records and the New Zealand Ministry of Health. RESULTS: One-year post hospital discharge cost of care was mean (95% CI) $US4706 (3758-6014) for the Take Charge intervention group and $6118 (4350-8005) for control, mean (95% CI) difference $ -1412 (-3553 to +729). Health utility scores were mean (95% CI) 0.75 (0.73-0.77) for Take Charge and 0.71 (0.67-0.75) for control, mean (95% CI) difference 0.04 (0.0-0.08). Cost per QALY gained for the Take Charge intervention was $US -35,296 (=£ -25,524, € -30,019). Sensitivity analyses confirm Take Charge is cost-effective, even at a very low willingness-to-pay threshold. With a threshold of $US5000 per QALY, the probability that Take Charge is cost-effective is 99%. CONCLUSION: Take Charge is cost-effective and probably cost saving.

Switching to Tenecteplase for Stroke Thrombolysis: Real-World Experience and Outcomes in a Regional Stroke Network.

Background and Purpose: Due to practical advantages, increasing trial safety data, recent Australian Guideline endorsement and local population needs we switched to tenecteplase for stroke thrombolysis from alteplase. We describe our change process and real-world outcome data. Methods: Mixed-methods including stakeholder engagement, preimplementation and postimplementation surveys, and assessment of patient treatment rates, metrics, and clinical outcomes preimplementation and postimplementation adjusting regression analyses for age, sex, National Institutes of Health Stroke Scale, premorbid modified Rankin Scale score, and thrombectomy using New Zealand National Stroke Registry data. Results: Preswitch consultation involved stroke and emergency clinicians, pharmacists, national regulatory bodies, and hospital legal teams. All survey responders (90% response rate) supported the proposed change and remained satisfied 12 months postimplementation. Between January 2018 and February 2021, we treated 555 patients with alteplase and 283 with tenecteplase. Patients treated with tenecteplase had greater odds of a favorable modified Rankin Scale using both shift (adjusted odds ratio, 1.60 [95% CI, 1.15­2.22]) and dichotomous analyses (modified Rankin Scale score, 0­2; adjusted odds ratio, 2.17 [95% CI, 1.31­3.59]) and shorter median (interquartile range) door-to-needle time (median, 53 [38­73.5] versus 61 minutes [45­85], P=0.0002). Symptomatic intracranial hemorrhage rates (tenecteplase 1.8% versus 3.4%; adjusted odds ratio, 0.46 [95% CI, 0.13­1.64]), death by day 7 (tenecteplase 7.5% versus 11.8%; adjusted odds ratio, 0.46 [95% CI, 0.21­0.99]), and median (interquartile range) needle to groin time for the 42 transferred regional patients (tenecteplase 155 [113­248] versus 200 [158­266]; P=0.27) did not significantly differ. Conclusions: Following stakeholder endorsement, a region-wide switch from alteplase to tenecteplase was successfully implemented. We found evidence of benefit and no evidence of harm.

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration.

BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.

The effect of the Take Charge intervention on mood, motivation, activation and risk factor management: Analysis of secondary data from the Taking Charge after Stroke (TaCAS) trial.

OBJECTIVE: To use secondary data from the Taking Charge after Stroke study to explore mechanisms for the positive effect of the Take Charge intervention on physical health, advanced activities of daily living and independence for people after acute stroke. DESIGN: An open, parallel-group, randomised trial with two active and one control intervention and blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: One, two, or zero sessions of the Take Charge intervention, a self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. MEASURES: Twelve months after stroke: Mood (Patient Health Questionnaire-2, Mental Component Summary of the Short Form 36); 'ability to Take Charge' using a novel measure, the Autonomy-Mastery-Purpose-Connectedness (AMP-C) score; activation (Patient Activation Measure); body mass index (BMI), blood pressure (BP) and medication adherence (Medication Adherence Questionnaire). RESULTS: Follow-up was near-complete (388/390 (99.5%)) of survivors at 12 months. Mean age (SD) was 72.0 (12.5) years. There were no significant differences in mood, activation, 'ability to Take Charge', medication adherence, BMI or BP by randomised group at 12 months. There was a significant positive association between baseline AMP-C scores and 12-month outcome for control participants (1.73 (95%CI 0.90 to 2.56)) but not for the Take Charge groups combined (0.34 (95%CI -0.17 to 0.85)). CONCLUSION: The mechanism by which Take Charge is effective remains uncertain. However, our findings support a hypothesis that baseline variability in motivation, mastery and connectedness may be modified by the Take Charge intervention.

Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke Care (REGIONS Care): Protocol for a Nationwide Observational Study.

BACKGROUND: Stroke systems of care differ between larger urban and smaller rural settings and it is unclear to what extent this may impact on patient outcomes. Ethnicity influences stroke risk factors and care delivery as well as patient outcomes in nonstroke settings. Little is known about the impact of ethnicity on poststroke care, especially in Maori and Pacific populations. OBJECTIVE: Our goal is to describe the protocol for the Reducing Ethnic and Geographic Inequities to Optimise New Zealand Stroke Care (REGIONS Care) study. METHODS: This large, nationwide observational study assesses the impact of rurality and ethnicity on best practice stroke care access and outcomes involving all 28 New Zealand hospitals caring for stroke patients, by capturing every stroke patient admitted to hospital during the 2017-2018 study period. In addition, it explores current access barriers through consumer focus groups and consumer, carer, clinician, manager, and policy-maker surveys. It also assesses the economic impact of care provided at different types of hospitals and to patients of different ethnicities and explores the cost-efficacy of individual interventions and care bundles. Finally, it compares manual data collection to routine health administrative data and explores the feasibility of developing outcome models using only administrative data and the cost-efficacy of using additional manually collected registry data. Regarding sample size estimates, in Part 1, Study A, 2400 participants are needed to identify a 10% difference between up to four geographic subgroups at 90% power with an α value of .05 and 10% to 20% loss to follow-up. In Part 1, Study B, a sample of 7645 participants was expected to include an estimated 850 Maori and 419 Pacific patients and to provide over 90% and over 80% power, respectively. Regarding Part 2, 50% of the patient or carer surveys, 40 provider surveys, and 10 focus groups were needed to achieve saturation of themes. The main outcome is the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes include mRS scores; EQ-5D-3L (5-dimension, 3-level EuroQol questionnaire) scores; stroke recurrence; vascular events; death; readmission at 3, 6, and 12 months; cost of care; and themes around access barriers. RESULTS: The study is underway, with national and institutional ethics approvals in place. A total of 2379 patients have been recruited for Part 1, Study A; 6837 patients have been recruited for Part 1, Study B; 10 focus groups have been conducted and 70 surveys have been completed in Part 2. Data collection has essentially been completed, including follow-up assessment; however, primary and secondary analyses, data linkage, data validation, and health economics analysis are still underway. CONCLUSIONS: The methods of this study may provide the basis for future epidemiological studies that will guide care improvements in other countries and populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25374.

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial.

INTRODUCTION: Nitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke. MATERIALS AND METHODS: Patients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI. RESULTS: In 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5%; p<0.001). Nitrate-related headache was associated with: younger age, female sex, higher diastolic blood pressure, non-total anterior circulation syndrome, milder stroke and absence of dysphasia (p<0.05). Nitrate headache was not associated with improved functional outcome (OR 0.90, 95% CI 0.73 to 1.10, p=0.30) or death (day 90) (HR 0.64, 95% CI 0.40 to 1.02, p=0.062), but reduced death or deterioration (day 7) (OR 0.45, 95% CI 0.25 to 0.82), death in hospital (OR 0.44, 95% CI 0.22 to 0.88) and improved activities of daily living (Barthel index, MD 3.7, 95% CI 0.3 to 7.1) and cognition (telephone interview cognitive screen, MD 2.0, 95% CI 0.7 to 3.3) (day 90). Non-nitrate headache was not associated with death, disability or cognition. DISCUSSION AND CONCLUSION: Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90, which was not seen with non-nitrate headache.

New Zealand hospital stroke service provision.

AIM: To describe stroke services currently offered in New Zealand hospitals and compare service provision in urban and non-urban settings. METHOD: An online questionnaire was sent to stroke lead clinicians at all New Zealand District Health Boards (DHBs). Questions covered number and location of stroke inpatients, stroke service configuration, use of guidelines/protocols, staffing mix, access to staff education, and culture appropriate care. RESULTS: There were responses from all 20 DHBs. Differences between urban and non-urban hospitals included: access to acute stroke units (55.6% non-urban vs 100% urban; p=0.013), stroke clinical nurse specialists (50% vs 90%; p=0.034), stroke clot retrieval (38.9% vs 80%; p=0.037) and Pacific support services (55.6% vs 100%; p=0.030). There were also differences in carer training (66.7% non-urban vs 100% urban; p=0.039) and goal-specific rehabilitation plans in the community (61.1% vs 100%; p=0.023). Access to TIA services, stroke rehabilitation units, early supported discharge, psychologists, continuing staff education, and culturally responsive stroke care were suboptimal irrespective of hospital location. CONCLUSION: Hospital location is associated with differences in stroke services provision across New Zealand and ongoing work is required to optimise consistent access to best practice care. These results, in conjunction with an ongoing (REGIONS Care) study, will be used to determine whether this affects patient outcomes.

Taking Charge after Stroke: A randomized controlled trial of a person-centered, self-directed rehabilitation intervention.

BACKGROUND AND PURPOSE: "Take Charge" is a novel, community-based self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. In a previous randomized controlled trial, a single Take Charge session improved independence and health-related quality of life 12 months following stroke in Maori and Pacific New Zealanders. We tested the same intervention in three doses (zero, one, or two sessions) in a larger study and in a broader non-Maori and non-Pacific population with stroke. We aimed to confirm whether the Take Charge intervention improved quality of life at 12 months after stroke in a different population and whether two sessions were more effective than one. METHODS: We randomized 400 people within 16 weeks of acute stroke who had been discharged to institution-free community living at seven centers in New Zealand to a single Take Charge session (TC1, n = 132), two Take Charge sessions six weeks apart (TC2, n = 138), or a control intervention (n = 130). Take Charge is a "talking therapy" that encourages a sense of purpose, autonomy, mastery, and connectedness with others. The primary outcome was the Physical Component Summary score of the Short Form 36 at 12 months following stroke comparing any Take Charge intervention to control. RESULTS: Of the 400 people randomized (mean age 72.2 years, 58.5% male), 10 died and two withdrew from the study. The remaining 388 (97%) people were followed up at 12 months after stroke. Twelve months following stroke, participants in either of the TC groups (i.e. TC1 + TC2) scored 2.9 (95% confidence intervals (CI) 0.95 to 4.9, p = 0.004) points higher (better) than control on the Short Form 36 Physical Component Summary. This difference remained significant when adjusted for pre-specified baseline variables. There was a dose effect with Short Form 36 Physical Component Summary scores increasing by 1.9 points (95% CI 0.8 to 3.1, p < 0.001) for each extra Take Charge session received. Exposure to the Take Charge intervention was associated with reduced odds of being dependent (modified Rankin Scale 3 to 5) at 12 months (TC1 + TC2 12% versus control 19.5%, odds ratio 0.55, 95% CI 0.31 to 0.99, p = 0.045). CONCLUSIONS: Confirming the previous randomized controlled trial outcome, Take Charge-a low-cost, person-centered, self-directed rehabilitation intervention after stroke-improved health-related quality of life and independence. CLINICAL TRIAL REGISTRATION-URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615001163594.

Imaging markers of small vessel disease and brain frailty, and outcomes in acute stroke.

OBJECTIVE: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS randomized 4,011 patients with acute stroke (<48 hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables. RESULTS: In all participants and those with lacunar syndrome (LACS; 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.24; brain frailty score OR 1.25, 95% CI 1.17-1.34; those with LACS: SVD score OR 1.30, 95% CI 1.15-1.47, brain frailty score OR 1.28, 95% CI 1.14-1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS. CONCLUSIONS: Baseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making. IDENTIFIER: ISRCTN99414122.

Associations between change in blood pressure and functional outcome, early events and death: results from the Efficacy of Nitric Oxide in Stroke trial.

OBJECTIVES: High blood pressure (BP) is associated with a poor outcome after acute stroke. Early reduction in BP may be associated with fewer early adverse events and deaths, and improved functional outcome. METHODS: Analyses used data from the Efficacy of Nitric Oxide in Stroke trial, a multicentre randomized single-masked and outcome-masked trial of glyceryl trinitrate vs. no glyceryl trinitrate in 4011 patients recruited within 48 h of an ischaemic or haemorrhagic stroke and with raised SBP (140-220 mmHg). Change in SBP from baseline to day 1 was categorized as: more than 15% decrease, 15-5% decrease, 5% decrease to 5% increase (no change - reference) and more than 5% increase. The primary outcome was functional outcome (modified Rankin scale) score at 90 days. RESULTS: Across all patients, both moderate (5-15%) and large (>15%) decreases in SBP were associated with beneficial shifts in the modified Rankin scale relative to patients with no change in BP: adjusted common odds ratio (OR) 0.81 [95% confidence interval (CI) 0.70-0.90] and OR 0.84 (95% CI 0.71-1.00), respectively. A moderate decrease in SBP was also associated with a lower risk of early adverse events, adjusted OR 0.69 (95% CI 0.52-0.90). CONCLUSION: Modest decreases in SBP in acute stroke appear to be associated with fewer early events and better long-term functional outcome.