Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis.

Background and purpose: Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with a prevalence of 14% in patients with newly diagnosed hypertension. Patients with PA experience a higher rate of cardiovascular events including stroke when compared to those with blood pressure matched essential hypertension. This systematic review and meta-analysis summarize current evidence on the prevalence of PA in patients with acute stroke or transient ischemic attack (TIA). Methods: Two reviewers independently reviewed the literature for observational studies on the prevalence of PA in patients with acute stroke or TIA. MEDLINE and Embase were searched for studies up to December 13, 2023. Results: Three single center studies conducted in Japan, Singapore and China were found to meet the inclusion criteria. The reported prevalence of PA in two cohort studies of adults with stroke or TIA were 3.1% and 4.0% and a third cross-sectional study in adults under 45 years old revealed a prevalence rate of 12.9%. Following a meta-analysis, the pooled prevalence of PA in adults with stroke or TIA is 5.8% [95% CI 1.6%-12.3%]. Conclusions: A considerable proportion of patients with stroke or TIA may have PA as the underlying cause of their hypertension. Given the increased risk of stroke associated with PA, clinicians should consider screening for PA in hypertensive patients with stroke or TIA. Further research is needed to evaluate the effect of timing and interfering medications on test results, which will inform an evidence-based approach to testing for PA following TIA or stroke. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328644.

Corrigendum: Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT).

[This corrects the article DOI: 10.3389/fnins.2023.1153231.].

Possible Influence of Ethnicity on CT Perfusion Parameter Thresholds in Acute Ischemic Stroke.

Introduction Tissue at risk, as estimated by CT perfusion utilizing Tmax+6, correlates with final infarct volume (FIV) in acute ischemic stroke (AIS) without reperfusion. Tmax thresholds are derived from Western ethnic populations but not from ethnic Asian populations. We aimed to investigate the influence of ethnicity on Tmax thresholds. Methods From a clinical-imaging registry of Australian and Indonesian stroke patients, we selected a participant subgroup with the following inclusion criteria: AIS under 24 hours and absence of reperfusion therapy. Clinical data included demographics, time metrics, stroke severity, premorbid, and 3-month Modified Rankin Score. Baseline CTP and MRI <72 hours were performed. Volumes of Tmax utilizing different thresholds and final infarct volumes (FIV) were calculated. Spearman correlation was used to evaluate relationship involving ordinal variables and calculate the optimal Tmax threshold against FIV in both populations. Results Two hundred patients were included in the study sample 100 in Jakarta and 100 in Geelong. The median National Institutes Health Stroke Scale (IQR) were 6(3-11) and 3(1-5), respectively. The median Tmax+6(IQR) was 0 (0-46.5) in Jakarta group and 0(0-7.5) in Geelong group. The median FIV(IQR) was 0 (0-30.5) and 0 (0-5.5). Tmax +8s in Jakarta population against FIV showed Spearman's coefficient =0.72, representing the optimal Tmax threshold. Tmax+6s showed Spearman's coefficient =0.51 against FIV in the Geelong population. Conclusions Tmax thresholds approximating FIV were possibly different in the Asian when compared with the non-Asian populations. Future studies are required to extend and confirm the validity of our findings.

Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT).

Background: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. Methods: The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2-8 × 106/kg, i.v.) on preventing immunosuppression after stroke. Results: Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload. Conclusion: Our Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial. Clinical trial registration: ClinicalTrials.gov, identifier ACTRN12618000076279P.

Convexity subarachnoid haemorrhage: a practical guide.

Atraumatic convexity subarachnoid haemorrhage describes spontaneous bleeding into the convexities of the brain sulci without parenchymal involvement. Its many causes include reversible cerebral vasoconstriction syndrome, cerebral sinus venous thrombosis, posterior reversible encephalopathy syndrome and (in older people) cerebral amyloid angiopathy. We describe the clinical and radiological features of non-traumatic convexity subarachnoid haemorrhage with its various presentations, causes, treatments and prognoses, and use clinical vignettes to highlight important clinical points and pitfalls.

Feedback of aggregate patient-reported outcomes (PROs) data to clinicians and hospital end users: findings from an Australian codesign workshop process.

OBJECTIVES: Patient-reported outcomes (PROs) are increasingly used to measure the patient's perspective of their outcomes following healthcare interventions. The aim of this study was to determine the preferred formats for reporting service-level PROs data to clinicians, researchers and managers to support greater utility of these data to improve healthcare and patient outcomes. SETTING: Healthcare professionals receiving PRO data feedback at the health service level. PARTICIPANTS: An interdisciplinary Project Working Group comprised of clinicians participated in three workshops to codesign reporting templates of summarised PRO data (modified Rankin Scale, EuroQol Five Dimension Descriptive System, EuroQol Visual Analogue Scale and Hospital Anxiety and Depression Scale) using a modified Delphi process. An electronic survey was then distributed to short list the preferred templates among a broad sample of clinical end users. A final workshop was undertaken with the Project Working Group to review results and reach consensus on the final templates. PRIMARY AND SECONDARY OUTCOME MEASURES: The recommendation of preferred PRO summary data feedback templates and guiding principles for reporting aggregate PRO data to clinicians was the primary outcome. A secondary outcome was the identification of perceived barriers and enablers to the use of PRO data in hospitals. For each outcome measure, quantitative and qualitative data were summarised. RESULTS: 31 Working Group members (19 stroke, 2 psychology, 1 pharmacy, 9 researchers) participated in the workshops, where 25/55 templates were shortlisted for wider assessment. The survey was completed by 114 end users. Strongest preferences were identified for bar charts (37/82 votes, 45%) and stacked bar charts (37/91 votes, 41%). At the final workshop, recommendations to enhance communication of PROs data for comparing health service performance were made including tailoring feedback to professional roles and use of case-mix adjustment to ensure fair comparisons. CONCLUSIONS: Our research provides guidance on PROs reporting for optimising data interpretation and comparing hospital performance.

Effect of the Coronavirus Disease 2019 Pandemic on the Quality of Stroke Care in Stroke Units and Alternative Wards: A National Comparative Analysis.

BACKGROUND AND PURPOSE: Changes to hospital systems were implemented from March 2020 in Australia in response to the coronavirus disease 2019 pandemic, including decreased resources allocated to stroke units. We investigate changes in the quality of acute care for patients with stroke or transient ischemic attack during the pandemic according to patients' treatment setting (stroke unit or alternate ward). METHODS: We conducted a retrospective cohort study of patients admitted with stroke or transient ischemic attack between January 2019 and June 2020 in the Australian Stroke Clinical Registry (AuSCR). The AuSCR monitors patients' treatment setting, provision of allied health and nursing interventions, prescription of secondary prevention medications, and discharge destination. Weekly trends in the quality of care before and during the pandemic period were assessed using interrupted time series analyses. RESULTS: In total, 18,662 patients in 2019 and 8,850 patients in 2020 were included. Overall, 75% were treated in stroke units. Before the pandemic, treatment in a stroke unit was superior to alternate wards for the provision of all evidence-based therapies assessed. During the pandemic period, the proportion of patients receiving a swallow screen or assessment, being discharged to rehabilitation, and being prescribed secondary prevention medications decreased by 0.58% to 1.08% per week in patients treated in other ward settings relative to patients treated in stroke units. This change represented a 9% to 17% increase in the care gap between these treatment settings during the period of the pandemic that was evaluated (16 weeks). CONCLUSIONS: During the first 6 months of the pandemic, widening care disparities between stroke units and alternate wards have occurred.

Long-term renal outcome post-multimodal computed tomography in stroke evaluation.

Recent studies have demonstrated the risk of contrast-associated acute kidney injury (CA-AKI) is low post-multimodal computed tomography (MMCT) in the evaluation of acute stroke. We provide a complementary study with long-term renal follow up. A retrospective analysis was performed on all suspected strokes from January 2019 to June 2020 for those who had undergone computed tomography angiography, computed tomography perfusion or both. We identified 776 cases, of which 538 were excluded. The incidence of CA-AKI was 7.6% (n/N = 18/238; 95% confidence interval = 4.2-11.0). All CA-AKI cases had renal confounders. No AKI at >30 days was found in 60.5% (n = 144) of all cases studied. The long-term renal outcome post-MMCT in stroke evaluation is favourable at >30 days.

Stroke in patients with cancer in the era of hyperacute stroke intervention.

BACKGROUND: The natural history of patients with stroke and cancer remains poorly understood in the modern era of hyperacute stroke therapies (recombinant tissue plasminogen activator and endovascular clot retrieval (ECR)). Prior to these advances in stroke treatment, a highly cited study reported median overall survival (mOS) 4.5 months after stroke in a cohort of patients with cancer (2004, n = 96). AIMS: Our hypothesis is that patients with stroke and cancer have better outcome than in earlier studies. METHODS: Retrospective analysis of admission to a tertiary Stroke Unit between January 2015 and September 2017 (n = 1910), evaluation of hospital records and cancer treatment records. Cancer was categorised as early stage (Stages I and II) and advanced stage (Stage III or IV) using the RD-Staging system. Survival analysis was performed in R. RESULTS: There were 143 stroke patients with cancer (62% male) with mean age 73.2 ± 12.5 years. Ischaemic stroke occurred in 74.1% and 45 of 106 (42.5%) patients received intravenous thrombolysis (34/45) and/or ECR (11/45). One patient who received ECR died within 30 days of stroke. Those with early stage disease had mOS of 19.6 months (interquartile range (IQR) 3.1-31.5 months) and in advanced stage cancer mOS was 2.5 months (IQR 0.4-6.3 months; P < 0.01). CONCLUSION: In the modern era of stroke therapy, our cohort of patients with advanced cancer has lower survival post-stroke compared to those with early stage cancer.

Treatment with Multiple Therapeutic Classes of Medication Is Associated with Survival after Stroke.

INTRODUCTION: Treatment with several therapeutic classes of medication is recommended for secondary prevention of stroke. We analyzed the associations between the number of classes of prevention medications supplied within 90 days after discharge for ischemic stroke (IS)/transient ischemic attack (TIA) and survival. METHODS: This is a retrospective cohort study of adults with first-ever IS/TIA (2010-2014) from the Australian Stroke Clinical Registry individually linked with data from national pharmaceutical and Medicare claims. Exposure was the number of classes of recommended medications, i.e., blood pressure-lowering, antithrombotic, or lipid-lowering agents, supplied to patients within 90 days after discharge for IS/TIA. The longitudinal association between the number of classes of medications and survival was evaluated with Cox proportional hazards regression models using the landmark approach. A landmark date of 90 days after hospital discharge was used to separate exposure and outcome periods, and only patients who survived until this date were included. RESULTS: Of 8,429 patients (43% female, median age 74 years, 80% IS), 607 (7%) died in the year following 90 days after discharge. Overall, 56% of patients were supplied all 3 classes of medications, 28% 2 classes of medications, 11% 1 class of medications, and 5% no class of medications. Compared to patients supplied all 3 medication classes, adjusted hazard ratios for all-cause mortality ranged from 1.43 (95% confidence interval [CI]: 1.18-1.72) in those supplied 2 medication classes to 2.04 (95% CI: 1.44-2.88) in those supplied with no medication class. DISCUSSION/CONCLUSION: Treatment with all 3 classes of guideline-recommended medications within 90 days after discharge was associated with better survival. Ongoing efforts are required to ensure optimal pharmacological intervention for secondary prevention of stroke.

Application of Machine Learning Techniques to Identify Data Reliability and Factors Affecting Outcome After Stroke Using Electronic Administrative Records.

Aim: To use available electronic administrative records to identify data reliability, predict discharge destination, and identify risk factors associated with specific outcomes following hospital admission with stroke, compared to stroke specific clinical factors, using machine learning techniques. Method: The study included 2,531 patients having at least one admission with a confirmed diagnosis of stroke, collected from a regional hospital in Australia within 2009-2013. Using machine learning (penalized regression with Lasso) techniques, patients having their index admission between June 2009 and July 2012 were used to derive predictive models, and patients having their index admission between July 2012 and June 2013 were used for validation. Three different stroke types [intracerebral hemorrhage (ICH), ischemic stroke, transient ischemic attack (TIA)] were considered and five different comparison outcome settings were considered. Our electronic administrative record based predictive model was compared with a predictive model composed of "baseline" clinical features, more specific for stroke, such as age, gender, smoking habits, co-morbidities (high cholesterol, hypertension, atrial fibrillation, and ischemic heart disease), types of imaging done (CT scan, MRI, etc.), and occurrence of in-hospital pneumonia. Risk factors associated with likelihood of negative outcomes were identified. Results: The data was highly reliable at predicting discharge to rehabilitation and all other outcomes vs. death for ICH (AUC 0.85 and 0.825, respectively), all discharge outcomes except home vs. rehabilitation for ischemic stroke, and discharge home vs. others and home vs. rehabilitation for TIA (AUC 0.948 and 0.873, respectively). Electronic health record data appeared to provide improved prediction of outcomes over stroke specific clinical factors from the machine learning models. Common risk factors associated with a negative impact on expected outcomes appeared clinically intuitive, and included older age groups, prior ventilatory support, urinary incontinence, need for imaging, and need for allied health input. Conclusion: Electronic administrative records from this cohort produced reliable outcome prediction and identified clinically appropriate factors negatively impacting most outcome variables following hospital admission with stroke. This presents a means of future identification of modifiable factors associated with patient discharge destination. This may potentially aid in patient selection for certain interventions and aid in better patient and clinician education regarding expected discharge outcomes.

Network Mapping of Time to Antithrombotic Therapy Among Patients With Ischemic Stroke and Transient Ischemic Attack (TIA).

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration. Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics. Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received "stat" (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4-3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2-20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0-16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (ß 0.20 ± 0.03, SV = 3.2), nasogastric tube (ß 19.8 ± 5.9, SV = -0.20), Alteplase (ß 8.6 ± 3.6, SV = -1.9), stat dose antithrombotic (ß -18.9 ± 2.9, SV = -10.8) and stroke code (ß -5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if "stat" dose of antithrombotics was given (coefficient = -0.32). Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.

COVID-19 Pandemic Impact on Care for Stroke in Australia: Emerging Evidence From the Australian Stroke Clinical Registry.

We present information on acute stroke care for the first wave of the COVID-19 pandemic in Australia using data from the Australian Stroke Clinical Registry (AuSCR). The first case of COVID-19 in Australia was recorded in late January 2020 and national restrictions to control the virus commenced in March. To account for seasonal effects of stroke admissions, patient-level data from the registry from January to June 2020 were compared to the same period in 2019 (historical-control) from 61 public hospitals. We compared periods using descriptive statistics and performed interrupted time series analyses. Perceptions of stroke clinicians were obtained from 53/72 (74%) hospitals participating in the AuSCR (80% nurses) via a voluntary, electronic feedback survey. Survey data were summarized to provide contextual information for the registry-based analysis. Data from the registry covered locations that had 91% of Australian COVID-19 cases to the end of June 2020. For the historical-control period, 9,308 episodes of care were compared with the pandemic period (8,992 episodes). Patient characteristics were similar for each cohort (median age: 75 years; 56% male; ischemic stroke 69%). Treatment in stroke units decreased progressively during the pandemic period (control: 76% pandemic: 70%, p < 0.001). Clinical staff reported fewer resources available for stroke including 10% reporting reduced stroke unit beds. Several time-based metrics were unchanged whereas door-to-needle times were longer during the peak pandemic period (March-April, 2020; 82 min, control: 74 min, p = 0.012). Our data emphasize the need to maintain appropriate acute stroke care during times of national emergency such as pandemic management.

An International Report on the Adaptations of Rapid Transient Ischaemic Attack Pathways During the COVID-19 Pandemic.

BACKGROUND: This report aims to describe changes that centres providing transient ischaemic attack (TIA) pathway services have made to stay operational in response to the SARS-CoV-2 pandemic. METHODS: An international cross-sectional description of the adaptions of TIA pathways between 30th March and 6th May 2020. Experience was reported from 18 centres with rapid TIA pathways in seven countries (Australia, France, UK, Canada, USA, New Zealand, Italy, Canada) from three continents. RESULTS: All pathways remained active (n = 18). Sixteen (89%) had TIA clinics. Six of these clinics (38%) continued to provide in-person assessment while the majority (63%) used telehealth exclusively. Of these, three reported PPE use and three did not. Five centres with clinics (31%) had adopted a different vascular imaging strategy. CONCLUSION: The COVID pandemic has led TIA clinics around the world to adapt and move to the use of telemedicine for outpatient clinic review and modified investigation pathways. Despite the pandemic, all have remained operational.

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

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

Current aspects of TIA management.

Transient Ischaemic Attack (TIA) if untreated carries a high risk of early stroke and is associated with poorer long-term survival [1]. There is emerging evidence of a reduction in stroke risk following TIA. Time critical investigations and management, as well as service organisation remain key to achieving good outcomes. Patients are diagnosed with TIA if they have transient, sudden-onset focal neurological symptoms which usually completely and rapidly resolve by presentation. The tissue based definition of TIA guides the fact that patients with residual symptoms should be considered as potentially having a stroke, with urgent evaluation regarding eligibility for thrombolysis and/or endovascular clot retrieval (ECR). Essential investigations for all patients with TIA should include early brain imaging, ECG, and carotid imaging in patients with anterior circulation symptoms. After brain imaging, exclusion of high risk indicators and immediate administration of an antiplatelet agent, subsequent attention to other mechanistic factors can be managed safely as part of a structured clinical pathway supervised by stroke specialists. This is in line with the recently revised Stroke Foundation Clinical Guidelines for Stroke Management (2017).

Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Stroke Severity Versus Dysphagia Screen as Driver for Post-stroke Pneumonia.

Background and Purpose: Post-stroke pneumonia is a feared complication of stroke as it is associated with greater mortality and disability than in those without pneumonia. Patients are often kept "Nil By Mouth" (NBM) after stroke until after receiving a screen for dysphagia and declared safe to resume oral intake. We aimed to assess the proportional contribution of stroke severity and dysphagia screen to pneumonia by borrowing idea from coalition game theory on fair distribution of marginal profit (Shapley value). Method: Retrospective study of admissions to the stroke unit at Monash Medical Center in 2015. Seventy-five percent of data were partitioned into training set and the remainder (25%) into validation set. Variables associated with pneumonia (p < 0.1) were entered into Shapley value regression and conditional decision tree analysis. Results: In 2015, there were 797 admissions and 617 patients with ischemic and hemorrhagic stroke (age 69.9 ± 16.2, male = 55.0%, National Institute of Health Stroke Scale/NIHSS 8.1 ± 7.9). The frequency of pneumonia was 6.6% (41/617). In univariable analyses NIHSS, time to dysphagia screen, Charlson comorbidity index (CCI), and age were significantly associated with pneumonia but not weekend admission. Shapley value regression showed that the largest contributor to the model was stroke severity (72.8%) followed by CCI (16.2%), dysphagia screen (3.8%), and age (7.2%). Decision tree analysis yielded an NIHSS threshold of 14 for classifying people with (27% of 75 patients) and without pneumonia (2.5% of 308 patients). The area under the ROC curve for training data was 0.83 (95% CI 0.75-0.91) with no detectable difference between the training and test data (p = 0.4). Results were similar when dysphagia was exchanged for the variable dysphagia screen. Conclusion: Stroke severity status, and not dysphagia or dysphagia screening contributed to the decision tree model of post stroke pneumonia. We cannot exclude the chance that using dysphagia screen in this cohort had minimized the impact of dysphagia on development of pneumonia.

Inferring the long duration response to levodopa in Parkinson's disease.

INTRODUCTION: The long duration response to levodopa in Parkinson's disease outlasts drug elimination by days to weeks. Though a substantive part of anti-parkinsonian motor benefit, it cannot easily be observed. OBJECTIVES: To infer the magnitude of the long duration response during the first decade of Parkinson's disease and identify factors that influence it. METHODS: Serial practically defined off scores of 24 patients from a longitudinal study of levodopa short duration response were used to establish their rate of motor progression. A line of notional untreated disability (as if drug treatment had never been given) with the same progression gradient was the basis for calculation of the long duration response. Predictors of mean long duration response amplitude were identified using a multiple linear regression model. RESULTS: Over a mean treatment period of 16.6 ±â€¯4.4 years, annual increase in motor disability was 2.3% of the maximum score. The long duration response composed 49% of total levodopa response during the first decade of treatment, and this proportion was significantly higher soon after commencing levodopa (p = 0.001). Higher pre-treatment motor score (r = 0.60) and lower MMSE (r = 0.60) were the main predictors of a larger long duration response. There was little correlation between long and short duration responses. CONCLUSIONS: Long duration responses contribute almost half of the total levodopa benefit during the first decade of treatment. An appreciation of both long and short duration components of drug symptomatic effects is important in clinical trial design to investigate possible neuroprotective treatments.