Sex differences in stroke reperfusion therapy in Aotearoa (New Zealand).

BACKGROUND AND AIMS: Stroke is a leading cause of death in Aotearoa (New Zealand), and stroke reperfusion therapy is a key intervention. Sex differences in stroke care have previously been asserted internationally. This study assessed potential differences in stroke reperfusion rates and quality metrics by sex in Aotearoa (New Zealand). METHODS: This study used data from three overlapping sources. The National Stroke Reperfusion Register provided 4-year reperfusion data from 2018 to 2021 on all patients treated with reperfusion therapy (intravenous thrombolysis and thrombectomy), including time delays, treatment rates, mortality and complications. Linkage to Ministry of Health administrative and REGIONS Care study data provided an opportunity to control for confounders and explore potential mechanisms. T-test and Wilcoxon rank-sum analyses were used for continuous variables, while the chi-squared test and logistic regression were used for comparing dichotomous variables. RESULTS: Fewer women presented with ischaemic stroke (12 186 vs 13 120) and were 4.2 years older than men (median (interquartile range (IQR)) 79 (68-86) vs 73 (63-82) years). Women were overall less likely to receive reperfusion therapy (13.9% (1704) vs 15.8% (2084), P < 0.001) with an adjusted odds ratio of 0.83 (0.77-0.90), P < 0.001. The adjusted odds ratio for thrombolysis was lower for women (0.82 (0.76-0.89), P < 0.001), but lower rates of thrombectomy fell just short of statistical significance ((0.89 (0.79-1.00), P = 0.05). There were no significant differences in complications, delays or documented reasons for non-thrombolysis. CONCLUSIONS: Women were less likely to receive thrombolysis, even after adjusting for age and stroke severity. We found no definitive explanation for this disparity.

Management of Poststroke Hyperglycemia: Results of the TEXAIS Randomized Clinical Trial.

BACKGROUND: Hyperglycemia in acute ischemic stroke reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin-based therapies are difficult to implement and may cause hypoglycemia. We investigated whether exenatide, a GLP-1 (glucagon-like peptide-1) receptor agonist, would improve stroke outcomes, and control poststroke hyperglycemia with minimal hypoglycemia. METHODS: The TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke) was an international, multicenter, phase 2 prospective randomized clinical trial (PROBE [Prospective Randomized Open Blinded End-Point] design) enrolling adult patients with acute ischemic stroke ≤9 hours of stroke onset to receive exenatide (5 µg BID subcutaneous injection) or standard care for 5 days, or until hospital discharge (whichever sooner). The primary outcome (intention to treat) was the proportion of patients with ≥8-point improvement in National Institutes of Health Stroke Scale score (or National Institutes of Health Stroke Scale scores 0-1) at 7 days poststroke. Safety outcomes included death, episodes of hyperglycemia, hypoglycemia, and adverse event. RESULTS: From April 2016 to June 2021, 350 patients were randomized (exenatide, n=177, standard care, n=173). Median age, 71 years (interquartile range, 62-79), median National Institutes of Health Stroke Scale score, 4 (interquartile range, 2-8). Planned recruitment (n=528) was stopped early due to COVID-19 disruptions and funding constraints. The primary outcome was achieved in 97 of 171 (56.7%) in the standard care group versus 104 of 170 (61.2%) in the exenatide group (adjusted odds ratio, 1.22 [95% CI, 0.79-1.88]; P=0.38). No differences in secondary outcomes were observed. The per-patient mean daily frequency of hyperglycemia was significantly less in the exenatide group across all quartiles. No episodes of hypoglycemia were recorded over the treatment period. Adverse events of mild nausea and vomiting occurred in 6 (3.5%) exenatide patients versus 0 (0%) standard care with no withdrawal. CONCLUSIONS: Treatment with exenatide did not reduce neurological impairment at 7 days in patients with acute ischemic stroke. Exenatide did significantly reduce the frequency of hyperglycemic events, without hypoglycemia, and was safe to use. Larger acute stroke trials using GLP-1 agonists such as exenatide should be considered. REGISTRATION: URL: www.australianclinicaltrials.gov.au; Unique identifier: ACTRN12617000409370. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03287076.

The hereditary spastic paraplegias.

The hereditary spastic paraplegias (HSPs) are a group of more than 90 genetic disorders in which lower extremity spasticity and weakness are either the primary neurologic impairments ("uncomplicated HSP") or when accompanied by other neurologic deficits ("complicated HSP"), important features of the clinical syndrome. Various genetic types of HSP are inherited such as autosomal dominant, autosomal recessive, X-linked, and maternal (mitochondrial) traits. Symptoms that begin in early childhood may be nonprogressive and resemble spastic diplegic cerebral palsy. Symptoms that begin later, typically progress insidiously over a number of years. Genetic testing is able to confirm the diagnosis for many subjects. Insights from gene discovery indicate that abnormalities in diverse molecular processes underlie various forms of HSP, including disturbance in axon transport, endoplasmic reticulum morphogenesis, vesicle transport, lipid metabolism, and mitochondrial function. Pathologic studies in "uncomplicated" HSP have shown axon degeneration particularly involving the distal ends of corticospinal tracts and dorsal column fibers. Treatment is limited to symptom reduction including amelioration of spasticity, reducing urinary urgency, proactive physical therapy including strengthening, stretching, balance, and agility exercise.

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.

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.

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.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Clinical outcomes of delayed mechanical thrombectomy: Descriptive analysis and development of a screening tool.

BACKGROUND AND PURPOSE: Limited data guide the selection of patients with large vessel occlusion ischaemic stroke who may benefit from referral to a distant tertiary centre for mechanical thrombectomy (MT). We aimed to characterize this population, describe clinical outcomes and develop a screening system to identify patients most likely to benfit from delayed mechanical thrombectomy (MT). METHODS: We undertook a retrospective cohort analysis enrolling patients transferred from regional sites to one of two MT comprehensive stroke units with a time from non-contrast computed tomography (NCCT) of the brain to reperfusion of 4 h or more. We describe Alberta Stroke Programme Early Computed Tomography Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) in our patients and compare these patients to those in extended-time-window trials. Lastly, we developed and validated a scoring model to help clinicians identify appropriate patients based on variables associated with poor outcomes. RESULTS: We included 563 patients, 46% of whom received thrombolysis; the median (interquartile range [IQR]) ASPECTS was 8 (7-10) and the median (IQR) NIHSS score was 16 (11-20). The median (IQR) symptom to mechanical reperfusion time was 390 (300-580) min. Eight patients (1%) had a symptomatic haemorrhage. We achieved good clinical outcome (defined as mRS score ≤2) in 299 patients (54%). Age, diabetes, NIHSS score and ASPECTS were used to create a weighted scoring system with a validated area under the curve of 0.83 (95% confidence interval 0.74-0.92). CONCLUSION: Our study shows, in highly selected patients, that delayed MT many hours after baseline NCCT is associated with good clinical outcomes. However, older patients with diabetes, high NIHSS score and low ASPECTS may not benefit from transfer to a hub centre many hours away for MT in this model of care.

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.

Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST.

BACKGROUND: Familial hereditary spastic paraplegia (HSP)-SPAST (SPG4) typically presents with a pure HSP phenotype. OBJECTIVE: The aim of this study was to delineate the genotypic and phenotypic spectrum of children with de novo HSP-SPAST. METHODS: This study used a systematic cross-sectional analysis of clinical and molecular features. RESULTS: We report the clinical and molecular spectrum of 40 patients with heterozygous pathogenic de novo variants in SPAST (age range: 2.2-27.7 years). We identified 19 unique variants (16/40 carried the same recurrent variant, p.Arg499His). Symptom onset was in early childhood (median: 11.0 months, interquartile range: 6.0 months) with significant motor and speech delay, followed by progressive ascending spasticity, dystonia, neurogenic bladder dysfunction, gastrointestinal dysmotility, and epilepsy. The mean Spastic Paraplegia Rating Scale score was 32.8 ± 9.7 (standard deviation). CONCLUSIONS: These results confirm that de novo variants in SPAST lead to a severe and complex form of HSP that differs from classic familial pure HSP-SPAST. Clinicians should be aware of this syndrome in the differential diagnosis for cerebral palsy. © 2022 International Parkinson and Movement Disorder Society.

Impact considerations of post-production processes on cell and gene drug products.

Cell and gene therapies are demonstrating clinical efficacy, but prohibitive product costs and operational complexity bottlenecks may limit expanded patient access to these innovative and transformative products. An initial survey and subsequent article published through the International Society for Cell & Gene Therapy in 2017 presented a roadmap on how specific steps, from tissue procurement and material acquisition to facility operation and production, contribute to the high cost of cell and gene therapies. Herein the authors expanded the investigation to provide considerations to better understand how post-production procedures can impact a product's accessibility to patients. The administration of a drug product to and follow-up in a patient involve key decisions in several post-production process areas, such as product storage, distribution and handling logistics and compliance, across the value chain through integrated data management solutions. Understanding as well as carefully evaluating these specific components is not widely considered during early process development but is critical in developing a viable product life cycle.

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.

Fever-Associated Seizures or Epilepsy: An Overview of Old and Recent Literature Acquisitions.

In addition to central nervous system infections, seizures and fever may occur together in several neurological disorders. Formerly, based on the clinical features and prognostic evolution, the co-association of seizure and fever included classical febrile seizures (FS) divided into simple, complex, and prolonged FS (also called febrile status epilepticus). Later, this group of disorders has been progressively indicated, with a more inclusive term, as "fever-associated seizures or epilepsy" (FASE) that encompasses: (a) FS divided into simple, complex, and prolonged FS; (b) FS plus; (c) severe myoclonic epilepsy in infancy (Dravet syndrome); (d) genetic epilepsy with FS plus; and (e) febrile infection-related epilepsy syndrome (FIRES). Among the FASE disorders, simple FS, the most common and benign condition, is rarely associated with subsequent epileptic seizures. The correlation of FS with epilepsy and other neurological disorders is highly variable. The pathogenesis of FASE is unclear but immunological and genetic factors play a relevant role and the disorders belonging to the FASE group show to have an underlying common clinical, immunological, and genetic pathway. In this study, we have reviewed and analyzed the clinical data of each of the heterogeneous group of disorders belonging to FASE.

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.

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).

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.

Hereditary Myelopathies.

PURPOSE OF REVIEW: This article guides clinicians in the clinical recognition and differential diagnosis of hereditary myelopathies. RECENT FINDINGS: Rather than a disease, a disease process, or relating to specific cellular vulnerability, the term hereditary myelopathy refers to diverse inherited disorders in which major aspects of the clinical syndrome reflect disturbance of elements within the spinal cord (specifically, the dorsal columns and dorsal root ganglia, corticospinal tracts, and anterior horn cells). It is important to note that the clinical features of almost all hereditary myelopathies reflect not only disturbance of elements within the spinal cord but also disturbance of extraspinal structures (particularly, but not limited to, peripheral nerves and the cerebellum) and that these extraspinal clinical features can be very helpful in recognizing specific myelopathy syndromes. The value of classifying disorders as inherited myelopathies lies primarily in facilitating their clinical recognition and differential diagnosis. It is useful to recognize that many hereditary myelopathies conform to one of four clinical paradigms: (1) spinocerebellar ataxia, (2) motor neuron disorder, (3) leukodystrophy, or (4) distal motor-sensory axonopathy predominantly affecting the central nervous system. Although they are myelopathies, spinal dysraphisms such as spina bifida and myelomeningocele are not included in this context because they are not usually due to single-gene mutation and have low hereditability. SUMMARY: This article illustrates clinical paradigms of hereditary myelopathy with clinical examples emphasizing the spectrum, clinical recognition, and differential diagnosis of hereditary myelopathies.

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.