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Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a life-threatening monogenic autoimmune disorder primarily caused by biallelic deleterious variants in the autoimmune regulator ( AIRE ) gene. We prospectively evaluated 104 patients with clinically diagnosed APECED syndrome and identified 17 patients (16%) from 14 kindreds lacking biallelic AIRE variants in exons or flanking intronic regions; 15 had Puerto Rican ancestry. Through whole-genome sequencing, we identified a deep intronic AIRE variant (c.1504-818 G>A) cosegregating with the disease in all 17 patients. We developed a culture system of AIRE -expressing primary patient monocyte-derived dendritic cells and demonstrated that c.1504-818 G>A creates a cryptic splice site and activates inclusion of a 109-base pair frame-shifting pseudoexon. We also found low-level AIRE expression in patient-derived lymphoblastoid cell lines (LCLs) and confirmed pseudoexon inclusion in independent extrathymic AIRE -expressing cell lines. Through protein modeling and transcriptomic analyses of AIRE -transfected human embryonic kidney 293 and thymic epithelial cell 4D6 cells, we showed that this variant alters the carboxyl terminus of the AIRE protein, abrogating its function. Last, we developed an antisense oligonucleotide (ASO) that reversed pseudoexon inclusion and restored the normal AIRE transcript sequence in LCLs. Thus, our findings revealed c.1504-818 G>A as a founder APECED-causing AIRE variant in the Puerto Rican population and uncovered pseudoexon inclusion as an ASO-reversible genetic mechanism underlying APECED.

Background: Although the incidence and case-fatality of subarachnoid haemorrhage (SAH) vary within countries, few countries have reported nationwide rates, especially for multi-ethnic populations. We assessed the nationwide incidence and case-fatality of SAH in New Zealand (NZ) and explored variations by sex, district, ethnicity and time., Methods: We used administrative health data from the national hospital discharge and cause-of-death collections to identify hospitalised and fatal non-hospitalised aneurysmal SAHs in NZ between 2001 and 2018. For validation, we compared these administrative data to those of two prospective Auckland Regional Community Stroke Studies. We subsequently estimated the incidence and case-fatality of SAH and calculated adjusted rate ratios (RR) with 95% confidence intervals to assess differences between sub-populations., Findings: Over 78,187,500 cumulative person-years, we identified 5371 SAHs (95% sensitivity and 85% positive predictive values) resulting in an annual age-standardised nationwide incidence of 8.2/100,000. In total, 2452 (46%) patients died within 30 days after SAH. Compared to European/others, Māori had greater incidence (RR = 2.23 (2.08-2.39)) and case-fatality (RR = 1.14 (1.06-1.22)), whereas SAH incidence was also greater in Pacific peoples (RR = 1.40 (1.24-1.59)) but lesser in Asians (RR = 0.79 (0.71-0.89)). By domicile, age-standardised SAH incidence varied between 6.3-11.5/100,000 person-years and case fatality between 40 and 57%. Between 2001 and 2018, the SAH incidence of NZ decreased by 34% and the case fatality by 12%., Interpretation: Since the incidence and case-fatality of SAH varies considerably between regions and ethnic groups, caution is advised when generalising findings from focused geographical locations for public health planning, especially in multi-ethnic populations., Funding: NZ Health Research Council., Competing Interests: IR received research grants from the Sigrid Juselius Foundation, the Finnish Medical Foundation, the Sakari Alhopuro Foundation, the Finnish Foundation for Cardiovascular Research and the Maud Kuistila Foundation. AR received grant funding from the New Zealand Health Research Council and the Ministry of Health. JD is funded from grants awarded by the New Zealand Health Research Council and the New Zealand Royal Society Marsden Fund. PAB report a leadership or fiduciary role as a President of Australia and New Zealand Association of Neurologists. The authors report no other declarations., (© 2024 The Author(s).)

The assessment of bone marrow iron stores is typically performed on an aspirate smear slide that has been manually stained by a technologist using a commercially available kit. This approach can contribute to inconsistent results and limit the broad use of iron staining in bone marrow specimens, particularly when laboratories have low staffing and/or high specimen volumes. Here, we describe the adaptation and validation of the Ventana Benchmark automated stainer and iron stain kit for routine clinical use of staining iron in bone marrow aspirate smear slides. We assessed accuracy and precision of the Ventana automated iron staining protocol compared to the Perls Prussian blue manual iron staining index method. Hematopathologists assigned Gale scores and enumerated the percentages of erythroid sideroblasts on paired patient bone marrow aspirate smear slides stained by the automated method and the manual iron staining method. We found a similar level of performance of the Ventana automated iron stain relative to the index manual method (as assessed by Pearson correlation and Bland-Altman analyses). In addition, there was low imprecision between replicates performed via the automated iron stain protocol. We also report superior qualitative findings of the automated method in ease of localization of iron storage, visualization of sideroblasts, and counterstain consistency. Automated iron staining of bone marrow aspirate smear slides performed similarly to the manual method and may allow for accurate routine evaluation of bone marrow iron stores as part of bone marrow analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Seagrasses provide critical ecosystem services but cumulative human pressure on coastal environments has seen a global decline in their health and extent. Key processes of anthropogenic disturbance can operate at local spatio-temporal scales that are not captured by conventional satellite imaging. Seagrass management strategies to prevent longer-term loss and ensure successful restoration require effective methods for monitoring these fine-scale changes. Current seagrass monitoring methods involve resource-intensive fieldwork or recurrent image classification. This study presents an alternative method using iteratively reweighted multivariate alteration detection (IR-MAD), an unsupervised change detection technique originally developed for satellite images. We investigate the application of IR-MAD to image data acquired using an unoccupied aerial vehicle (UAV). UAV images were captured at a 14-week interval over two seagrass beds in Brisbane Water, NSW, Australia using a 10-band Micasense RedEdge-MX Dual camera system. To guide sensor selection, a further three band subsets representing simpler sensor configurations (6, 5 and 3 bands) were also analysed using eight categories of seagrass change. The ability of the IR-MAD method, and for the four different sensor configurations, to distinguish the categories of change were compared using the Jeffreys-Matusita (JM) distance measure of spectral separability. IR-MAD based on the full 10-band sensor images produced the highest separability values indicating that human disturbances (propeller scars and other seagrass damage) were distinguishable from all other change categories. IR-MAD results for the 6-band and 5-band sensors also distinguished key seagrass change features. The IR-MAD results for the simplest 3-band sensor (an RGB camera) detected change features, but change categories were not strongly separable from each other. Analysis of IR-MAD weights indicated that additional visible bands, including a coastal blue band and a second red band, improve change detection. IR-MAD is an effective method for seagrass monitoring, and this study demonstrates the potential for multispectral sensors with additional visible bands to improve seagrass change detection., (© 2024. The Author(s).)

Aims: To describe the clinical features and outcomes of patients with myelopathy and neuropathy due to recreationally inhaled nitrous oxide., Methods: We identified patients presenting with nitrous oxide-associated myelopathy from an electronic database of all discharges in a large tertiary hospital between 2016 and 2023. Demographics, clinical features and the results of investigations were recorded. The primary outcome was modified Rankin Scale score (mRS) at least 3 months after hospital discharge where available., Results: There were 12 patients identified, six women, mean (SD) age 27.5 (5.1) years, range 19-47 years. The most common symptoms were numbness, weakness and mental state changes. Four patients used large amounts of inhaled nitrous oxide and also took over-the-counter vitamin B12 supplements. The median (range) hospital length of stay was 8.5 (2-56) days. Functional independence at last assessment (median [range] of 3 [1-34] months after discharge) was achieved in nine of the patients, with three requiring ongoing support for activities of daily living (mRS ≥3)., Conclusion: Nitrous oxide abuse and its neurological complications are an important public health issue. Clinicians should be aware that some patients who use large amounts of nitrous oxide may self-supplement vitamin B12., Competing Interests: The authors have no conflicts of interest to declare., (© PMA.)

Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity., Competing Interests: Potential conflicts of interest. T.M. is an employee of Matinas Biopharma and has an equity interest and receives support for attending meetings and/or travel and reports a role as board director for Apilli Therapeutics and GoodCap Pharmaceuticals. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH-90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy., Methods and Results: Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH-90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS-90) was assessed with in-person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59-79], median National Institutes of Health Stroke Scale score 14 [9-20]). Median DAOH-90 was 71 [29-84] and median mRS-90 score was 3 [2-5]. DAOH-90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho -0.44, P <0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24, P <0.001). There was a strong association between mRS-90 and DAOH-90 (Spearman rho correlation -0.79, P <0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84-0.88), mRS score >1 was 0.88 (95% CI, 0.86-0.90) and mRS score >2 was 0.90 (95% CI, 0.89-0.92)., Conclusions: In patients with stroke treated with reperfusion therapies, DAOH-90 shows reasonable comparability to the more established outcome measure of mRS-90. DAOH-90 can be readily obtained from administrative databases and therefore has the potential to be used in large-scale clinical trials and comparative effectiveness studies.

Thoracic outlet syndrome (TOS) involves inconsistent symptoms, presenting a challenge for medical providers to diagnose and treat. Thoracic outlet syndrome is defined as a compression injury to the brachial plexus, subclavian artery or vein, or axillary artery or vein occurring between the cervical spine and upper extremity. Three common subcategories are now used for clinical diagnosis: neurogenic, arterial, and venous. Postural position and repetitive motions such as throwing, weightlifting, and manual labor can lead to symptoms. Generally, TOS is considered a diagnosis of exclusion for athletes due to the poor accuracy of clinical testing, including sensitivity and specificity. Thus, determining a definitive diagnosis and reporting injury is difficult. Current literature suggests there is not a gold standard diagnostic test. Rehabilitation has been shown to be a vital component in the recovery process for neurogenic TOS and for arterial TOS and venous TOS in postoperative situations., (© by the National Athletic Trainers' Association, Inc.)

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., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood., Methods: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire -/- Ifng -/- mice and Aire -/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses., Results: Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire -/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire -/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients., Conclusions: Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Objectives: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial., Methods: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome., Results: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 ( r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3., Discussion: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT., Classification of Evidence: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Background and Purpose: Infarcts in acute ischemic stroke (AIS) patients may continue to grow even after reperfusion, due to mechanisms such as microvascular obstruction and reperfusion injury. We investigated whether and how much infarcts grow in AIS patients after near-complete (expanded Thrombolysis in Cerebral Infarction [eTICI] 2c/3) reperfusion following endovascular treatment (EVT), and to assess the association of post-reperfusion infarct growth with clinical outcomes., Methods: Data are from a single-center retrospective observational cohort study that included AIS patients undergoing EVT with near-complete reperfusion who received diffusion-weighted magnetic resonance imaging (MRI) within 2 hours post-EVT and 24 hours after EVT. Association of infarct growth between 2 and 24 hours post-EVT and 24-hour National Institutes of Health Stroke Scale (NIHSS) as well as 90-day modified Rankin Scale score was assessed using multivariable logistic regression., Results: Ninety-four of 155 (60.6%) patients achieved eTICI 2c/3 and were included in the analysis. Eighty of these 94 (85.1%) patients showed infarct growth between 2 and 24 hours post-reperfusion. Infarct growth ≥5 mL was seen in 39/94 (41.5%) patients, and infarct growth ≥10 mL was seen in 20/94 (21.3%) patients. Median infarct growth between 2 and 24 hours post-reperfusion was 4.5 mL (interquartile range: 0.4-9.2 mL). Post-reperfusion infarct growth was associated with the 24-hour NIHSS in multivariable analysis (odds ratio: 1.16 [95% confidence interval 1.09-1.24], P<0.01)., Conclusion: Infarcts continue to grow after EVT, even if near-complete reperfusion is achieved. Investigating the underlying mechanisms may inform future therapeutic approaches for mitigating the process and help improve patient outcome.

Purpose: Diffusion-weighted imaging (DWI) lesion expansion after endovascular thrombectomy (EVT) is not well characterized. We used serial diffusion-weighted magnetic resonance imaging (MRI) to measure lesion expansion between 2 and 24 h after EVT., Methods: In this single-center observational analysis of patients with acute ischemic stroke due to large vessel occlusion, DWI was performed post-EVT (< 2 h after closure) and 24-h later. DWI lesion expansion was evaluated using multivariate generalized linear mixed modeling with various clinical moderators., Results: We included 151 patients, of which 133 (88%) had DWI lesion expansion, defined as a positive change in lesion volume between 2 and 24 h. In an unadjusted analysis, median baseline DWI lesion volume immediately post-EVT was 15.0 mL (IQR: 6.6-36.8) and median DWI lesion volume 24 h post-EVT was 20.8 mL (IQR: 9.4-66.6), representing a median change of 6.1 mL (IQR: 1.5-17.7), or a 39% increase. There were no significant associations among univariable models of lesion expansion. Adjusted models of DWI lesion expansion demonstrated that relative lesion expansion (defined as final/initial DWI lesion volume) was consistent across eTICI scores (0-2a, 0.52%; 2b, 0.49%; 2c-3, 0.42%, p = 0.69). For every 1 mL increase in lesion volume, there was 2% odds of an increase in 90-day mRS (OR: 1.021, 95%CI [1.009, 1.034], p < 0.001)., Conclusion: We observed substantial lesion expansion post-EVT whereby relative lesion expansion was consistent across eTICI categories, and greater absolute lesion expansion was associated with worse clinical outcome. Our findings suggest that alternate endpoints for cerebroprotectant trials may be feasible., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Deep learning using clinical and imaging data may improve pre-treatment prognostication in ischemic stroke patients undergoing endovascular thrombectomy (EVT)., Methods: Deep learning models were trained and tested on baseline clinical and imaging (CT head and CT angiography) data to predict 3-month functional outcomes in stroke patients who underwent EVT. Classical machine learning models (logistic regression and random forest classifiers) were constructed to compare their performance with the deep learning models. An external validation dataset was used to validate the models. The MR PREDICTS prognostic tool was tested on the external validation set, and its performance was compared with the deep learning and classical machine learning models., Results: A total of 975 patients (550 men; mean±SD age 67.5±15.1 years) were studied with 778 patients in the model development cohort and 197 in the external validation cohort. The deep learning model trained on baseline CT and clinical data, and the logistic regression model (clinical data alone) demonstrated the strongest discriminative abilities for 3-month functional outcome and were comparable (AUC 0.811 vs 0.817, Q=0.82). Both models exhibited superior prognostic performance than the other deep learning (CT head alone, CT head, and CT angiography) and MR PREDICTS models (all Q<0.05)., Conclusions: The discriminative performance of deep learning for predicting functional independence was comparable to logistic regression. Future studies should focus on whether incorporating procedural and post-procedural data significantly improves model performance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health., Methods: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study., Results: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations., Discussion: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building., Registration Information: PROSPERO registration: CRD42021242367.

Background and Objectives: Evidence of effective multifactorial lifestyle interventions for primary stroke prevention is lacking, despite the significant contribution of lifestyle to stroke burden. We aimed to determine the efficacy of health and wellness coaching (HWC) for primary stroke and cardiovascular disease (CVD) prevention in adults at a moderate-to-high CVD risk., Methods: This was a parallel, 2-arm, open-label, single-blinded, phase III randomized controlled trial to determine the efficacy of HWC for primary stroke prevention in individuals 30 years and older with a 5-year CVD risk ≥10% as measured by 5-year absolute CVD risk (as measured by the PREDICT tool) at 9 months post-randomization. Eligible participants were those with a 5-year CVD risk ≥10%, with no history of stroke, transient ischemic attack, or myocardial infarction. The relative risk reduction (RRR) and odds ratios (OR) were evaluated separately in those at moderate (10%-14%) 5-year CVD risk and those at high risk (≥15%) at baseline. The Life's Simple 7 (LS7) score for lifestyle-related CVD risk, as the indicator of cardiovascular health, was a key secondary outcome., Results: Of a total of 320 participants, 161 were randomized to the HWC group and 159 to the usual care (UC) group. HWC resulted in a statistically significant RRR of -10.9 (95% CI -21.0 to -0.9) in 5-year CVD risk in the higher CVD risk group but no change in the moderate risk group. An improvement in the total LS7 score was seen in the HWC group compared with the UC group (absolute difference = 0.485, 95% CI [0.073 to 0.897], p = 0.02). Improvement in blood pressure scores was statistically significantly greater in the HWC group than in the UC group for those at high risk of CVD (OR 2.28 [95% CI 1.12 to 4.63] and 1.55 [0.80 to 3.01], respectively). No statistically significant differences in mood scores, medication adherence, quality of life, and satisfaction with life scores over time or between groups were seen., Discussion: Health and wellness coaching resulted in a significant RRR in the 5-year CVD risk compared with UC at 9 months post-randomization in patients with a high baseline CVD risk. There was no improvement in CVD risk in the moderate risk group; hence, this study did not meet the primary hypothesis. However, this treatment effect is clinically significant (number needed to treat was 43). The findings suggest that HWC has potential if further refined to improve lifestyle risk factors of stroke., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Objectives: The neuroprotectant nerinetide has shown promise in reducing infarct volumes in primate models of ischemia reperfusion. We hypothesized that early secondary infarct growth after endovascular therapy (EVT) (1) may be a suitable surrogate biomarker for testing neuroprotective compounds, (2) is feasible to assess in the acute setting using sequential MRI, and (3) can be modified by treatment with nerinetide., Methods: REPERFUSE-NA1 was a prospective, multisite MRI substudy of the randomized controlled trial ESCAPE-NA1 (ClinicalTrials.gov NCT02930018) that involved patients with acute disabling large vessel occlusive stroke undergoing EVT within 12 hours of onset who were randomized to receive intravenous nerinetide or placebo. Patients enrolled in REPERFUSE-NA1 underwent sequential MRI <5 hours post-EVT (day 1) and at 24 hours (day 2). The primary outcome was total diffusion-weighted MRI infarct growth early after EVT, defined as the lesion volume difference between day 2 and day 1. The secondary outcome was region-specific infarct growth in different brain tissue compartments. Statistical analyses were performed using the Mann-Whitney U test and multiple linear regression., Results: Sixty-seven of 71 patients included had MRI of sufficient quality. The median infarct volume post-EVT was 12.98 mL (IQR, 5.93-28.08) in the nerinetide group and 10.80 mL (IQR, 3.11-24.45) in the control group ( p = 0.59). Patients receiving nerinetide showed a median early secondary infarct growth of 5.92 mL (IQR, 1.09-21.30) compared with 10.80 mL (interquartile range [IQR], 2.54-21.81) in patients with placebo ( p = 0.30). Intravenous alteplase modified the effect of nerinetide on region-specific infarct growth in white matter and basal ganglia compartments. In patients with no alteplase, the infarct growth rate was reduced by 120% (standard error [SE], 60%) in the white matter ( p = 0.03) and by 340% (SE, 140%) in the basal ganglia ( p = 0.02) in the nerinetide group compared with placebo after adjusting for confounders., Discussion: This study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acute stroke treatment. Patients with acute large vessel occlusive stroke exhibited appreciable early infarct growth both in the gray matter and the white matter after undergoing EVT. Acknowledging relatively small overall infarct volumes in this study, treatment with nerinetide was associated with slightly reduced percentage infarct growth in the white matter and basal ganglia compared with placebo in patients not receiving intravenous alteplase and had no effect on the total early secondary infarct growth., Trial Registration Information: ClinicalTrials.gov NCT02930018., Classification of Evidence: This study provides Class II evidence that for patients with acute large vessel ischemic stroke undergoing EVT, nerinetide did not significantly decrease early post-EVT infarct growth compared with placebo.

In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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, Māori, 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 Māori, 369 Pacific Peoples, and 354 Asians experienced a stroke during the study period. Median age was 65 years for Māori and Pacific Peoples, and 71 and 79 years for Asians and NZ Europeans, respectively. Compared with NZ Europeans, Māori 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). Māori 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.

Objective: To identify which subjective and objective tests do content experts utilize to help guide return to sport (RTS) decision making for an athlete after an upper extremity (UE) injury?, Methods: A modified Delphi survey was utilized, including content experts in UE rehabilitation. Survey items were identified based on a literature review identifying current best evidence and practice for UE RTS decision making. Content experts (n = 52) were identified, having a minimum of 10 years of experience with rehabilitation of UE athletic injuries, and 5 years of experience using an UE RTS algorithm to guide decision making., Results: Expert consensus was achieved on a combination of tests utilized within an UE RTS algorithm: 1. Tissue healing time frame is an important consideration in RTS decision making; 2. Patient reported outcome measures should be utilized specifically, DASH and NPRS 3. Strength is measured by handheld dynamometer and is an important consideration. 4. ROM should be utilized and is an important consideration. 5. Physical performance tests utilized include: Closed Kinetic Chain Upper Extremity Stability test, Seated shot-put test and lower extremity/core tests., Conclusions: This survey reached expert consensus on which subjective and objective measures to utilize to evaluate RTS readiness after UE injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent., Methods: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www., Clinicaltrials: gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase., Results: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I 2 =0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I 2 =0%), 0.77 ([95% CI, 0.53-1.14]; I 2 =0%), and 2.31 ([95% CI, 0.69-7.75]; I 2 =40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I 2 =0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I 2 =1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I 2 =52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents., Conclusions: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

Background and Objectives: Endovascular thrombectomy (EVT) for large vessel occlusion ischemic stroke is either performed under general anesthesia (GA) or with non-GA techniques such as conscious sedation or local anesthesia alone. Previous small meta-analyses have demonstrated superior recanalization rates and improved functional recovery with GA when compared with non-GA techniques. The publication of further randomized controlled trials (RCTs) could provide updated guidance when choosing between GA and non-GA techniques., Methods: A systematic search for trials in which stroke EVT patients were randomized to GA or non-GA was performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials. A systematic review and meta-analysis using a random-effects model was performed., Results: Seven RCTs were included in the systematic review and meta-analysis. These trials included a total of 980 participants (GA, N = 487; non-GA, N = 493). GA improves recanalization by 9.0% (GA 84.6% vs non-GA 75.6%; odds ratio [OR] 1.75, 95% CI 1.26-2.42, p = 0.0009), and the proportion of patients with functional recovery improves by 8.4% (GA 44.6% vs non-GA 36.2%; OR 1.43, 95% CI 1.04-1.98, p = 0.03). There was no difference in hemorrhagic complications or 3-month mortality., Discussion: In patients with ischemic stroke treated with EVT, GA is associated with higher recanalization rates and improved functional recovery at 3 months compared with non-GA techniques. Conversion to GA and subsequent intention-to-treat analysis will underestimate the true therapeutic benefit. GA is established as effective in improving recanalization rates in EVT (7 Class 1 studies) with a high Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) certainty rating. GA is established as effective in improving functional recovery at 3 months in EVT (5 Class 1 studies) with a moderate GRADE certainty rating. Stroke services need to develop pathways to incorporate GA as the first choice for most EVT procedures in acute ischemic stroke with a level A recommendation for recanalization and level B recommendation for functional recovery., (© 2023 American Academy of Neurology.)

Background and Aims: Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles., Methods: Patients with TIA ( N  = 49) and seventy-nine ( N  = 79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100 g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF., Results: Patients with TIA had significantly ( p  < 0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex ( p  = 0.03), right posterior cingulate ( p  = 0.04), and right precuneus ( p  = 0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p  = 0.05 for both regions) and slower processing speed (TMT A, p  = 0.04 and p  = 0.01), respectively after adjusting for age and sex., Conclusions: TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies., Competing Interests: The Authors declare that there is no conflict of interest., (© 2023 The Author(s).)

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

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.

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

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.

Background: We describe the first-in-human experience using the Route 92 Medical Aspiration System to perform thrombectomy in the initial 45 consecutive stroke patients enrolled in the SUMMIT NZ trial. This aspiration system includes a specifically designed delivery catheter which enables delivery of 0.070 inch and 0.088 inch aspiration catheters., Methods: The SUMMIT NZ trial is a prospective, multicenter, single-arm study with core lab imaging adjudication. Patients presenting with acute ischemic stroke from large vessel occlusion are eligible to enrol. The study has had three phases which transitioned from use of the 0.070 inch to the 0.088 inch catheter., Results: Vessel occlusions were located in the internal carotid artery (27%), M1 (60%) and M2 (13%). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 10). Across the three phases, the first-pass reperfusion rate of modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b was 62% using the Route 92 Medical system; this rate was 29% in phase 1, 56% in phase 2, and 80% in phase 3. The first-pass reperfusion rate of mTICI ≥2c was 42% overall, 29% in phase 1, 33% in phase 2, and 55% in phase 3. A final reperfusion rate of mTICI ≥2b was achieved in 96% of cases, with 36% of cases using adjunctive devices. Patients had an average improvement of 6.7 points in NIHSS from baseline at 24 hours, and at 90 days 48% were functionally independent (modified Rankin Scale 0-2)., Conclusions: In this early experience, the Route 92 Medical Aspiration System has been effective and safe. The system has design features that improve catheter deliverability and have the potential to increase first-pass reperfusion rates in aspiration thrombectomy., Competing Interests: Competing interests: The study investigators were not remunerated for their involvement in this study or the production of the manuscript. Dr Brew, Dr McGuinness, Dr Caldwell and Dr Lee have consulting agreements with Route 92 Medical., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Thoracic outlet syndrome (TOS) involves an inconsistent set of symptoms that provides a challenge for medical providers to treat. Three categories of TOS are neurogenic, arterial, and venous. A combination of symptoms can occur and are most seen in overhead athletes. Symptoms may include pain, numbness, of an athlete to perform at their prior level of sport is impacted. Due to the variance in presentation and poor objective testing, there is not a well-defined examination process. It is suggested to perform an individualized assessment for each athlete. An athlete's medical team must communicate effectively as numerous specialists are usually involved to create a comprehensive treatment plan. Rehabilitation has been identified as a vital component in the recovery process. As an athletic trainer it is imperative to identify TOS and coordinate with the athlete's care team.

Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = -0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = -0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = -1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.

Registration: Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p., Rationale: Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery., Aim: To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension., Design: Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes., Procedures: Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with 'wake up' stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist., Study Outcomes: The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days., Analysis: The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Background and Objectives: International evidence shows that patients treated at nonurban hospitals experience poorer access to key stroke interventions. Evidence for 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 outcomes of patients with stroke and access to best-practice stroke care in New Zealand., Methods: This is a prospective, multicenter, nationally representative observational study involving all 28 New Zealand acute stroke hospitals (18 nonurban) and affiliated rehabilitation and community services. Consecutive adults admitted to the hospital with acute stroke between May 1 and October 31, 2018, were captured. Outcomes included functional outcome (modified Rankin Scale [mRS] score shift analysis), functional independence (mRS score 0-2), quality of life (EuroQol 5-dimension, 3-level health-related quality of life questionnaire), 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, comorbid conditions, baseline function, and differences in baseline characteristics., Results: Overall, 2,379 patients were eligible (mean [SD] age 75 [13.7] years; 51.2% male; 1,430 urban, 949 nonurban). Patients treated at nonurban hospitals were more likely to score in a higher mRS score category (greater disability) at 3 (adjusted odds ratio [aOR] 1.28, 95% CI 1.07-1.53), 6 (aOR 1.33, 95% CI 1.07-1.65), and 12 (aOR 1.31, 95% CI 1.06-1.62) months and were more likely to have died (aOR 1.57, 95% CI 1.17-2.12) or experienced recurrent stroke and vascular events at 12 months (aOR 1.94, 95% CI 1.14-3.29 and aOR 1.65, 95% CI 1.09-2.52). Fewer nonurban patients received recommended stroke interventions, including endovascular thrombectomy (aOR 0.25, 95% CI 0.13-0.49), acute stroke unit care (aOR 0.60, 95% CI 0.49-0.73), antiplatelet prescriptions (aOR 0.72, 95% CI 0.58-0.88), ≥60 minutes of daily physical therapy (aOR 0.55, 95% CI 0.40-0.77), and community rehabilitation (aOR 0.69, 95% CI 0.56-0.84)., Discussion: Patients managed at nonurban 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 nonurban hospitals should be a priority., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aim: The aim of this study was to explore the perspectives of people with stroke and their whānau 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 whānau 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 whānau, improved communication across the patient journey, and a concerted effort to improve culturally safe care. Next step is to implement and monitor these recommendations., Competing Interests: The study was funded by the Health Research Council of New Zealand (HRC 17/037). Some of the authors receive other grant funding, but none that relates to this study, and report no competing interests.

Background: Most undergraduate medical students (UMS) do not receive any formal exposure to quality improvement (QI) efforts in healthcare during the entirety of their undergraduate programme. This is despite the rising interest amongst UMS and the unique potential that UMS hold as an innovator unencumbered by previous biases. To explore this, we implemented an undergraduate training programme that provides experiential QI education., Approach: The 15-week Summer Healthcare Improvement Programme (SHIP) was established in 2017, supported by a regional physician QI leadership coalition, a QI consultant preceptor who is linked to both the local university and health organisation and an UMS leadership group. Students were assigned QI projects that were aligned with the health organisation's purpose and scope. Students co-led the project to completion with mentorship from both physician QI leaders, and residents. Student competencies were formatively assessed by completing QI activities and a programme survey., Results: From 2017 to 2019, 19 students completed 22 QI projects, academic posters and publications, and all received QI certification. The majority (72%) of students felt involvement in SHIP increased their QI knowledge and skills, 90% believed SHIP would benefit their peers, and 71% of students felt it directly applied to their future careers., Discussion: Benefits of the programme were threefold: provided students with early experiential QI exposure, provided student QI leaders who possess dedicated time and effort to complete projects over the summer months and provided a physician QI learning continuum implemented with minimal to no additional cost to either the university or health organisation., (© 2022 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Introduction: This study aimed to develop and validate a 3-year dementia risk score in individuals with mild cognitive impairment (MCI) based on variables collected in routine clinical care., Methods: The prediction score was trained and developed using data from the National Alzheimer's Coordinating Center (NACC). Selection criteria included aged 55 years and older with MCI. Cox models were validated externally using two independent cohorts from the Prospective Registry of Persons with Memory Symptoms (PROMPT) registry and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database., Results: Our Mild Cognitive Impairment to Dementia Risk (CIDER) score predicted dementia risk with c-indices of 0.69 (95% confidence interval [CI] 0.66-0.72), 0.61 (95% CI 0.59-0.63), and 0.72 (95% CI 0.69-0.75), for the internally validated and the external validation PROMPT, and ADNI cohorts, respectively., Discussion: The CIDER score could be used to inform clinicians and patients about the relative probabilities of developing dementia in patients with MCI., Competing Interests: The authors have no conflicts of interest to report., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: Patellofemoral pain (PFP) is common and has a poor long-term prognosis. There is a lack of clarity about the clinical reasoning of recognised inter-disciplinary experts in the published literature., Objectives: To help identify best practice by exploring the clinical reasoning of a range of inter-disciplinary experts that regularly diagnose and treat PFP., Design: Qualitative study with semi-structured interviews., Method: Recruitment resulted in a convenience sample for semi-structured interview, which were recorded and transcribed verbatim. Data were analysed until theoretical saturation, as determined by multiple investigators., Findings: Interviews with 19 clinical experts (15 men, 4 women; mean experience 18.6 years ± 8.6) from four broad professions yielded four themes. Firstly, the assessment and diagnosis process should include a thorough history and examination to rule in PFP. Secondly, information provision should aim to increase patients' understanding, aid in controlling symptoms, and facilitate behaviour change. Thirdly, active rehabilitation, which was a salient theme and included advocacy of combined hip and knee exercise that is adapted to the individual. Finally, treatment adjuncts, which can be used selectively to modify symptoms, may include running retraining, taping, or foot orthoses., Conclusions: PFP should be diagnosed clinically, and tailored treatment programmes should be prescribed for people with PFP. Exercise was considered the most effective treatment and underlying psychological factors should be addressed to improve prognosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR., (© 2022. The Author(s).)

Aim: This study assessed stroke reperfusion treatments trends in 2019 and 2020 with comparison back to 2015. Additional analyses looked at differences by sex and ethnicity., Method: The National Stroke Register contains data on all stroke patients who received reperfusion therapies since 2015. Outcomes included treatment rates, delays, mortality and complications by year, sex, and ethnicity. Continuous variables were compared using the Wilcoxon Rank-Sum Test and presented as p-values. Rate-based results were compared using incidence rate comparison and presented as p-values +/- 95% confidence intervals., Results: In 2020, 11.3% (828/7333) received intravenous thrombolysis (IVT) and 5.5% (404/7333) underwent stroke clot retrieval (SCR), increasing from 6.5% (389/5963) and 0.5% (30/5963) in 2015, respectively. Among reperfused patients (IVT, SCR, both), 8.3% had died at seven days and 3.0% (29/959) experienced sICH. Door-to-treatment time was stable between 2019 and 2020, with median (IQR) of 61 (44-84) and 61 (41-87) minutes, respectively. Initial presentation to a SCR centre was associated with shorter onset-to-reperfusion time of 286 (206-566) minutes, compared with 403 (295-550) minutes (p<0.001). While onset-to-door time was shorter for Māori (72 (44-112) minutes, p<0.001) and Pacific patients (70 (48-105) minutes, p=0.03) compared with NZ Europeans, door-to-needle time was longer in Māori (66 (48-88) compared to 59 (41-83) minutes (p=0.001). Female (73.7+/15.3 years) patients were on average 4.4 years older than males (69.3+/-14.6 years) and less likely to receive thrombolysis (12.7% vs 14.9%, p=0.02)., Conclusion: Reperfusion therapy rates continue to rise, now driven by increasing rates of SCR. Longer door-to-needle time in Māori and lower reperfusion rates in women require further exploration and attention., Competing Interests: Nil.

Treatment with endovascular therapy in the extended time window for acute ischaemic stroke with large vessel occlusion involves stringent selection criteria based on the two landmark studies DAWN and DEFUSE3. Current protocols typically include the requirement of advanced perfusion imaging which may exclude a substantial proportion of patients from receiving a potentially effective therapy. Efforts to offer endovascular reperfusion therapies to all appropriate candidates may be facilitated by the use of simplified imaging selection paradigms with widely available basic imaging techniques, such as non-contrast CT and CT angiography. Currently available evidence from our literature review suggests that patients meeting simplified imaging selection criteria may benefit as much as those patients selected using advanced imaging techniques (CT perfusion or MRI) from endovascular therapy in the extended time window. A comprehensive understanding of the role of imaging in patient selection is critical to optimising access to endovascular therapy in the extended time window and improving outcomes in acute stroke. This article provides an overview on current developments and future directions in this emerging area., Competing Interests: Competing interests: CM, CD, and PB are cofounders of Andromeda Medical Imaging Inc.; PB reports consulting fees for Ablynx Pharmaceutical, and a Canadian Institutes of Health Research grant., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patellofemoral pain (PFP) is common and long-term treatment outcomes are unsatisfactory. Qualitative exploration of diagnosis and management from the perspective of people with PFP is lacking., Objectives: To inform care and improve intervention delivery by exploring the experience of people with PFP regarding diagnosis and management., Design: Qualitative study with semi-structured interviews., Method: Online recruiting yielded a convenience sample of participants with PFP for semi-structured interview. Interviews were recorded, transcribed verbatim, and analysed using thematic analysis until theoretical saturation by multiple investigators to determine themes and sub-themes., Results: 12 participants were interviewed, with three themes identified; the value of diagnosis, the need for tailored (individualised) care, and the role of education. Participants viewed receiving a diagnosis as essential to guide management, yet one was rarely provided, causing uncertainty about pain mechanisms; "it's nice to be told what it is that's wrong". Interventions needed to be tailored to the individual as not all participants responded in the same way to treatment(s) or had the same needs; "everyone copes and reacts differently". Finally, participants viewed education as essential to empower them to understand and manage the condition; "if I'd have been given more information, I think I'd know how to deal with it more"., Conclusions: The overarching narrative from three themes was a desire for clearly communicated personalised care that meets individual needs. People with PFP desire a diagnosis to explain their pain, tailored interventions, and appropriate education to optimise their experience and outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: Stroke clot retrieval (SCR) is now considered a standard of care for select stroke patients with proximal large vessel occlusion (LVO) of the anterior circulation. Here we present the experience of regional Taranaki patients transferred by air for SCR and compare this to metropolitan Auckland patients who were transferred by road. The aim is to present and compare process metrics and outcomes between the regional and metropolitan centres., Methods: This is a retrospective analysis of consecutive patients with anterior LVO transferred to Auckland City Hospital (ACH) for SCR from Taranaki, Waitematā and Counties Manukau district health boards (DHBs) between November 2017 and December 2020., Results: Thirty Taranaki patients were transferred for SCR, compared to 244 patients from Waitematā and Counties Manukau DHBs. Taranaki patients were seven years older and less ethnically diverse but similar in other characteristics. The proportion of patients with an independent Modified Rankin Scale (mRS) score between 0 and 2 at three months was the same as for the regional and metropolitan centres., Conclusions: In this real-world study, regional stroke patients can achieve similar SCR outcomes to metropolitan patients. Overcoming the post-code lottery for hyperacute stroke care can be achieved in a New Zealand setting., Competing Interests: P Alan Barber declares grants or contracts from University of Auckland within the past 36 months.

Background: Motor outcomes after stroke can be predicted using structural and functional biomarkers of the descending corticomotor pathway, typically measured using magnetic resonance imaging and transcranial magnetic stimulation, respectively. However, the precise structural determinants of intact corticomotor function are unknown. Identifying structure-function links in the corticomotor pathway could provide valuable insight into the mechanisms of post-stroke motor impairment. This study used supervised machine learning to classify upper limb motor evoked potential status using MRI metrics obtained early after stroke., Methods: Retrospective data from 91 patients (49 women, age 35-97 years) with moderate to severe upper limb weakness within a week after stroke were included in this study. Support vector machine classifiers were trained using metrics from T1- and diffusion-weighted MRI to classify motor evoked potential status, empirically measured using transcranial magnetic stimulation., Results: Support vector machine classification of motor evoked potential status was 81% accurate, with false positives more common than false negatives. Important structural MRI metrics included diffusion anisotropy asymmetry in the supplementary and pre-supplementary motor tracts, maximum cross-sectional lesion overlap in the sensorimotor tract and ventral premotor tract, and mean diffusivity asymmetry in the posterior limbs of the internal capsule., Interpretations: MRI measures of corticomotor structure are good but imperfect predictors of corticomotor function. Residual corticomotor function after stroke depends on both the extent of cross-sectional macrostructural tract damage and preservation of white-matter microstructural integrity. Analysing the corticomotor pathway using a multivariable MRI approach across multiple tracts may yield more information than univariate biomarker analyses., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: One-year risk of stroke in transient ischemic attack and minor stroke (TIAMS) managed in secondary care settings has been reported as 5-8%. However, evidence for the outcomes of TIAMS in community care settings is limited. Methods: The INternational comparison of Systems of care and patient outcomes In minor Stroke and TIA (INSIST) study was a prospective inception cohort community-based study of patients of 16 general practices in the Hunter-Manning region (New South Wales, Australia). Possible-TIAMS patients were recruited from 2012 to 2016 and followed-up for 12 months post-index event. Adjudication as TIAMS or TIAMS-mimics was by an expert panel. We established 7-days, 90-days, and 1-year risk of stroke, TIA, myocardial infarction (MI), coronary or carotid revascularization procedure and death; and medications use at 24 h post-index event. Results: Of 613 participants (mean age; 70 ± 12 years), 298 (49%) were adjudicated as TIAMS. TIAMS-group participants had ischemic strokes at 7-days, 90-days, and 1-year, at Kaplan-Meier (KM) rates of 1% (95% confidence interval; 0.3, 3.1), 2.1% (0.9, 4.6), and 3.2% (1.7, 6.1), respectively, compared to 0.3, 0.3, and 0.6% of TIAMS-mimic-group participants. At one year, TIAMS-group-participants had twenty-five TIA events (KM rate: 8.8%), two MI events (0.6%), four coronary revascularizations (1.5%), eleven carotid revascularizations (3.9%), and three deaths (1.1%), compared to 1.6, 0.6, 1.0, 0.3, and 0.6% of TIAMS-mimic-group participants. Of 167 TIAMS-group participants who commenced or received enhanced therapies, 95 (57%) were treated within 24 h post-index event. For TIAMS-group participants who commenced or received enhanced therapies, time from symptom onset to treatment was median 9.5 h [IQR 1.8-89.9]. Conclusion: One-year risk of stroke in TIAMS participants was lower than reported in previous studies. Early implementation of antiplatelet/anticoagulant therapies may have contributed to the low stroke recurrence., Competing Interests: NS was the recipient of co-funded National Health and Medical Research Council Career Development/National Heart Foundation Future Leader Fellowship (APP1110629/100827). VF's work was partly funded by the Health Research Council of New Zealand. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with author PR at time of review., (Copyright © 2021 Tomari, Levi, Holliday, Lasserson, Valderas, Dewey, Barber, Spratt, Cadilhac, Feigin, Rothwell, Zareie, Garcia-Esperon, Davey, Najib, Sales and Magin.)

Among the most economically relevant and environmentally devastating diseases globally are those caused by Phytophthora species. In Australia, production losses in agriculture and forestry result from several well-known cosmopolitan Phytophthora species and infestation of natural ecosystems by Phytophthora cinnamomi have caused irretrievable loss to biodiversity especially in proteaceous dominated heathlands. For this review, all available records of Phytophthora in Australia were collated and curated, resulting in a database of 7 869 records, of which 2 957 have associated molecular data. Australian databases hold records for 99 species, of which 20 are undescribed. Eight species have no records linked to molecular data, and their presence in Australia is considered doubtful. The 99 species reside in 10 of the 12 clades recognised within the complete phylogeny of Phytophthora. The review includes discussion on each of these species' status and additional information provided for another 29 species of concern. The first species reported in Australia in 1900 was Phytophthora infestans. By 2000, 27 species were known, predominantly from agriculture. The significant increase in species reported in the subsequent 20 years has coincided with extensive surveys in natural ecosystems coupled with molecular taxonomy and the recognition of numerous new phylogenetically distinct but morphologically similar species. Routine and targeted surveys within Australian natural ecosystems have resulted in the description of 27 species since 2009. Due to the new species descriptions over the last 20 years, many older records have been reclassified based on molecular identification. The distribution of records is skewed toward regions with considerable activity in high productivity agriculture, horticulture and forestry, and native vegetation at risk from P. cinnamomi. Native and exotic hosts of different Phytophthora species are found throughout the phylogeny; however, species from clades 1, 7 and 8 are more likely to be associated with exotic hosts. One of the most difficult challenges to overcome when establishing a pest status is a lack of reliable data on the current state of a species in any given country or location. The database compiled here for Australia and the information provided for each species overcomes this challenge. This review will aid federal and state governments in risk assessments and trade negotiations by providing a comprehensive resource on the current status of Phytophthora species in Australia. Citation: Burgess TI, Edwards J, Drenth A, et al. 2021. Current status of Phytophthora in Australia. Persoonia 47: 151-177. https://doi.org/10.3767/persoonia.2021.47.05., (© 2021 Naturalis Biodiversity Center & Westerdijk Fungal Biodiversity Institute.)

Introduction: Transient ischemic attack (TIA) and minor ischemic stroke (IS) is associated with a increased risk of late life dementia. In this study we aim to study the extent to which the rates of hippocampal atrophy in TIA/IS differ from healthy controls, and how they are correlated to neuropsychological measurements., Methods: TIA or minor stroke patients were tested with a neuropsychological battery including tests of executive function, and verbal and non-verbal memory at three time points out to 3 years. Annualized rates of hippocampal atrophy in TIA/IS patients were compared to controls. A linear-mixed regression model was used to assess the difference in rates of hippocampal atrophy after adjusting for time and demographic characteristics., Results: TIA/IS patients demonstrated a higher hippocampal atrophy rate than healthy controls over a 3-year interval: the annual percentage change of the left hippocampal volume was 2.5% (78 mm 3 per year (SD 60)) for TIA/IS patients compared to 0.9% (29 mm 3 per year (SD 32)) for controls ( p  < 0.01); and the annual percentage change of the right hippocampal volume was 2.5% (80 mm 3 per year (SD 46)) for TIA/IS patients compared to 0.5% (17 mm 3 per year (SD 33)) for controls ( P  < 0.01). Patients with higher annual hippocampal atrophy were more likely to report higher TMT B times, but lower ROC total score, lower California Verbal Learning Test-II total recall, and lower ROC Figure recall scores longitudinally., Conclusion: TIA/IS patients experience a higher rate of hippocampal atrophy independent of TIA/IS recurrence that are associated with changes in episodic memory and executive function over 3 years., Competing Interests: None, (© 2021 Published by Elsevier B.V.)

Objective: To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature., Methods: Searches were performed using MEDLINE, Embase, and Cochrane databases for studies that compared EVT with EVT with adjunctive IAT (EVT + IAT). Safety outcomes included symptomatic intracerebral hemorrhage and mortality at 3 months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b-3) and functional independence, defined as a modified Rankin Scale score of 0-2 at 3 months., Results: Five studies were identified that compared combined EVT + IAT (IA alteplase or urokinase) with EVT only and were included in the random-effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT + IAT and 1,424 patients receiving EVT only. Pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of symptomatic intracerebral hemorrhage (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.20-1.85; p = 0.78), mortality (OR: 0.77, 95% CI: 0.54-1.10; p = 0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52-2.15; p = 0.89). There was a higher rate of functional independence in patients treated with EVT + IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00-1.80; p = 0.053)., Conclusion: Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intra-arterial alteplase or urokinase as rescue therapy during EVT., (© 2021 American Academy of Neurology.)

Background: The COVID-19 pandemic has hit both the Spanish economy and the population's health hard. The result is an unprecedented economic and social crisis due to uncertainty about the remedy and the socioeconomic effects on people's lives., Methods: We performed a retrospective analysis of the macroeconomic impact of the COVID-19 pandemic in 2020 using key indicators of the Spanish economy for the 17 Autonomous Communities (ACs) of the country. National statistics were examined in the search for impacts or anomalies occurring since the beginning of the pandemic. To estimate the strength of the impact on each of the indicators analyzed, we used Bayesian structural time series. We also calculated the correlation between the rate of GDP decline during 2020 and the cumulative incidence of COVID-19 cases per 100,000 inhabitants in the ACs., Results: In 2020, the cumulative impact on the gross domestic product was of -11.41% (95% credible interval: -13.46; -9.29). The indicator for business turnover changed by -9.37% (-12.71; -6.07). The Spanish employment market was strongly affected; our estimates showed a cumulative increase of 11.9% (4.27; 19.45) in the rate of unemployment during 2020. The worst indicators were recorded in the ACs most economically dependent on the services sector. There was no statistical association between the incidence of COVID-19 in 2020 and the fall in GDP in the ACs., Conclusions: Our estimates portray a dramatic situation in Spain, where the COVID-19 crisis has had more serious economic and health consequences than in other European countries. The productive system in Spain is too dependent on sectors vulnerable to the pandemic, and it is necessary to design and implement profound changes through the European Next Generation program.