Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Left Atrial Appendage Thrombus Detected During Hyperacute Stroke Imaging Is Associated With Atrial Fibrillation.

BACKGROUND AND PURPOSE: Left atrial appendage (LAA) is the likely embolic source in atrial fibrillation (AF)-related cardioembolic strokes. We sought to determine the prevalence of LAA thrombus on hyperacute stroke imaging and its association with AF. METHODS: We retrospectively examined the clinical and radiological features of patients assessed through the hyperacute stroke imaging pathway over a 12-month period at Christchurch Hospital. The LAA was included in the computed tomography angiogram scan-range as part of the multimodal imaging protocol. Two radiological readers blinded to clinical information independently assessed for the presence of LAA thrombus. The association between AF and LAA thrombus was determined by multivariable logistic regression analysis. RESULTS: Of 303 patients included in the analysis, the overall prevalence of LAA thrombus was 6.6% and 14.9% in patients with known AF. Patients with LAA thrombus were older (85 versus 75 years, P<0.01), more commonly had known or newly diagnosed AF (75% versus 30%, P<0.01) and heart failure (30% versus 8%, P=0.01), and was associated with intracranial large vessel occlusion (65% versus 39%, P=0.02). In the multivariable model, AF (odds ratio, 3.71 [95% CI, 1.25-11.01] P=0.02) was independently associated with LAA thrombus after adjusting for age and congestive heart failure. Interrater reliability was moderate (kappa=0.56). CONCLUSIONS: LAA thrombus is a potential radiological marker of AF and can be assessed as a part of hyperacute stroke imaging.

Dabigatran Reversal Before Intravenous Tenecteplase in Acute Ischemic Stroke.

Background and Purpose- Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods- We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results- We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69-85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4-21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57-113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0-2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions- Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.

Combining forces to manage the continuum of care.

Many healthcare organizations are pursuing affiliation strategies to effectively manage population health. Healthcare organizations should take the following key steps in setting such a strategy: Ensuring the strategy aligns with the organization's mission Identifying potential partners. Outlining expectations for the affiliation. Assessing affiliation structure options.

Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.

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.

Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis.

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders. Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11-21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0-2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p < 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p = 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p < 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p = 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34-0.69, p < 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54-1.29, p = 0.45) after adjusting for confounders. Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.

Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Integration without employment.

Three models for hospital-physician alignment may offer hospitals for which large-scale physician employment is not practical the best means to prepare for payment changes under accountable care: Comanagement arrangements Clinical joint ventures Professional services agreements with performance incentives.

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).

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.

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.

From acquisition to integration: transforming a hospital into an ACO.

Five steps are essential to the process of hospitals acquiring physician groups to develop truly integrated delivery systems: Securing internal and external approvals. Integrating physicians into leadership and governance. Developing physician employment terms and compensation. Exploiting reimbursement improvement opportunities. Streamlining operations

Successful intravenous thrombolysis for ischemic stroke as a complication of coronary intervention in patients with ticagrelor pretreatment.

Ticagrelor is an antiplatelet agent used for treatment of coronary artery disease via inhibition of the P2Y12 receptor. Based on limited literature the safety of intravenous thrombolysis for ischemic stroke in patients with ticagrelor pretreatment is unknown. We present two patients established on ticagrelor treated with intravenous thrombolysis for acute ischemic stroke complicating coronary intervention.

Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET).

BACKGROUND AND PURPOSE: Reperfusion and recanalization have both been used as surrogate markers of clinical outcome in trials of stroke thrombolysis. We aimed to prove that the beneficial impact of recanalization with intravenous tissue plasminogen activator on clinical outcomes is attributable to reperfusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator in the 3- to 6-hour window. Reperfusion was defined as >90% reduction in magnetic resonance perfusion-weighted imaging lesion volume and recanalization as improvement of MR angiographic Thrombolysis In Myocardial Infarction grading by > or =2 points from baseline to Day 3 to 5. RESULTS: At Day 3 to 5, reperfusion and recanalization with intravenous tissue plasminogen activator were strongly correlated. Reperfusion was associated with improved clinical outcome independent of whether recanalization occurred. In contrast, recanalization was not associated with clinical outcome when reperfusion was included as a covariate in regression analyses. CONCLUSIONS: Reperfusion is a surrogate marker of clinical outcomes independent of recanalization based on the criteria applied in EPITHET. The impact of recanalization on clinical outcomes was attributable to reperfusion.

Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine.

PURPOSE: Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS: We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS: Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS: Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.

The Dysphagia in Stroke Protocol Reduces Aspiration Pneumonia in Patients with Dysphagia Following Acute Stroke: a Clinical Audit.

Cough reflex testing has been evaluated as a component of the clinical swallowing assessment as a means of identifying patients at risk of aspiration during swallowing. A previous study by our research group found good sensitivity and specificity of the cough reflex test for identifying patients at risk of aspiration post-stroke, yet its use did not decrease pneumonia rates, contrary to previous reports. The aim of this study was to expand on our earlier work by implementing a clinical management protocol incorporating cough reflex testing within the same healthcare setting and compare patient outcomes to those from the original study and to evaluate clinical outcomes in patients with acute stroke who were managed using the Dysphagia in Stroke Protocol (DiSP). Secondarily, to compare those outcomes to historical data prior to implementation of the DiSP. This clinical audit measured outcomes from 284 patients with acute stroke managed per the DiSP, which guides use of videofluoroscopic swallowing study and patient management based on clinical exam with cough reflex testing. Data from our previous trial were included for comparison of pre- and post-DiSP patient outcomes. Data collection took place between November 2012 and April 2016 at four urban hospitals within New Zealand. Following implementation of the DiSP, the rate of aspiration pneumonia (10%) was substantially lower than the pre-DiSP rate (28%), with no pneumonia readmissions within 3 months. Pneumonia-related mortality was unchanged. By 3 months, 81% of the patients were on a normal diet and 67% had returned home, compared to pre-DiSP outcomes of 55% and 55% respectively. Previous work has suggested that simply implementing cough reflex testing in dysphagia management may not be sufficient to improve patient outcomes. The present study adds to this picture by suggesting that the true variable of influence may be the way in which the results of the test are applied to patient care. There is a strong case to support the use of a structured protocol if cough reflex testing is to be implemented in clinical practice.

Does hemispheric lateralization influence functional and cardiovascular outcomes after stroke?: an analysis of placebo-treated patients from prospective acute stroke trials.

BACKGROUND AND PURPOSE: The influence of stroke lateralization on functional and cardiovascular outcome after stroke is not well established. We evaluated the influence of hemispheric lateralization among patients enrolled in prospective acute stroke trials. METHODS: We obtained data from the VISTA database for acute stroke trials which reported lateralization. Baseline data, cardiac adverse events, and 90-day outcomes were compared between right and left hemisphere stroke patients. A "hemisphere unbiased" subscore of the NIHSS which omitted items strongly associated with lateralized cognitive deficits was also compared for trials which reported individual NIHSS item scores. A multivariable analysis of outcome predictors was performed. RESULTS: Three acute stroke trials met the prespecified inclusion criteria. 1644 placebo-treated patients with documented hemispheric lateralization were included in the analysis. Baseline NIHSS was higher for left hemisphere patients (mean 16.2, versus 12.8 right, P<0.001); there was no difference in the "hemisphere unbiased" NIHSS subscore (10.88 left, 11.08 right, n=687, P=0.49). There was no difference between hemispheres in 90-day modified Rankin Score (3.43 left, 3.29 right, P=0.13), mortality (22.1% left, 19.5% right, P=0.20), or cardiac adverse events (P=0.71). Hemispheric lateralization was not an independent predictor of outcome in the multivariable analysis after controlling for the hemispheric bias intrinsic to the NIHSS. CONCLUSIONS: There is no difference in functional outcome between patients with right or left hemisphere stroke. Use of the baseline NIHSS score to predict stroke outcome must take hemispheric lateralization into account. Stroke lateralization is not an important predictor of cardiac adverse events or 90-day mortality.