Sex Differences in Prehospital Identification of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Differences in clinical presentation of acute ischemic stroke between men and women may affect prehospital identification of anterior circulation large vessel occlusion (aLVO). We assessed sex differences in diagnostic performance of 8 prehospital scales to detect aLVO. METHODS: We analyzed pooled individual patient data from 2 prospective cohort studies (LPSS [Leiden Prehospital Stroke Study] and PRESTO [Prehospital Triage of Patients With Suspected Stroke Study]) conducted in the Netherlands between 2018 and 2019, including consecutive patients ≥18 years suspected of acute stroke who presented within 6 hours after symptom onset. Ambulance paramedics assessed clinical items from 8 prehospital aLVO detection scales: Los Angeles Motor Scale, Rapid Arterial Occlusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Cincinnati Prehospital Stroke Scale, Prehospital Acute Stroke Severity, gaze-face-arm-speech-time, Conveniently Grasped Field Assessment Stroke Triage, and Face-Arm-Speech-Time Plus Severe Arm or Leg Motor Deficit. We assessed the diagnostic performance of these scales for identifying aLVO at prespecified cut points for men and women. RESULTS: Of 2358 patients with suspected stroke (median age, 73 years; 47% women), 231 (10%) had aLVO (100/1114 [9%] women and 131/1244 [11%] men). The area under the curve of the scales ranged from 0.70 (95% CI, 0.65-0.75) to 0.77 (95% CI, 0.73-0.82) in women versus 0.69 (95% CI, 0.64-0.73) to 0.75 (95% CI, 0.71-0.79) in men. Positive predictive values ranged from 0.23 (95% CI, 0.20-0.27) to 0.29 (95% CI, 0.26-0.31) in women versus 0.29 (95% CI, 0.24-0.33) to 0.37 (95% CI, 0.32-0.43) in men. Negative predictive values were similar (0.95 [95% CI, 0.94-0.96] to 0.98 [95% CI, 0.97-0.98] in women versus 0.94 [95% CI, 0.93-0.95] to 0.96 [95% CI, 0.94-0.97] in men). Sensitivity of the scales was slightly higher in women than in men (0.53 [95% CI, 0.43-0.63] to 0.76 [95% CI, 0.68-0.84] versus 0.49 [95% CI, 0.40-0.57] to 0.63 [95% CI, 0.55-0.73]), whereas specificity was lower (0.79 [95% CI, 0.76-0.81] to 0.87 [95% CI, 0.84-0.89] versus 0.82 [95% CI, 0.79-0.84] to 0.90 [95% CI, 0.88-0.91]). Rapid arterial occlusion evaluation showed the highest positive predictive values in both sexes (0.29 in women and 0.37 in men), reflecting the different event rates. CONCLUSIONS: aLVO scales show similar diagnostic performance in both sexes. The rapid arterial occlusion evaluation scale may help optimize prehospital transport decision-making in men as well as in women with suspected stroke.

Comparison of Prehospital Assessment by Paramedics and In-Hospital Assessment by Physicians in Suspected Stroke Patients: Results From 2 Prospective Cohort Studies.

BACKGROUND: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians. METHODS: We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (rs) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference. RESULTS: We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (rs=0.70 [95% CI, 0.68-0.72]). Concerning individual items, prehospital assessment of arm (rs=0.68) and leg (rs=0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (rs=0.31), abnormal speech (rs=0.50), and gaze deviation (rs=0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), while abnormal speech had high sensitivity (85%) but lowest specificity (65%). CONCLUSIONS: The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.

Comparison of Prehospital Scales for Predicting Large Anterior Vessel Occlusion in the Ambulance Setting.

Importance: The efficacy of endovascular thrombectomy (EVT) for symptomatic large anterior vessel occlusion (sLAVO) sharply decreases with time. Because EVT is restricted to comprehensive stroke centers, prehospital triage of patients with acute stroke codes for sLAVO is crucial, and although several prediction scales are already in use, external validation, head-to-head comparison, and feasibility data are lacking. Objective: To conduct external validation and head-to-head comparisons of 7 sLAVO prediction scales in the emergency medical service (EMS) setting and to assess scale feasibility by EMS paramedics. Design, Setting, and Participants: This prospective cohort study was conducted between July 2018 and October 2019 in a large urban center in the Netherlands with a population of approximately 2 million people and included 2 EMSs, 3 comprehensive stroke centers, and 4 primary stroke centers. Participants were consecutive patients aged 18 years or older for whom an EMS-initiated acute stroke code was activated. Of 2812 acute stroke codes, 805 (28.6%) were excluded, because no application was used or no clinical data were available, leaving 2007 patients included in the analyses. Exposures: Applications with clinical observations filled in by EMS paramedics for each acute stroke code enabling reconstruction of the following 7 prediction scales: Los Angeles Motor Scale (LAMS); Rapid Arterial Occlusion Evaluation (RACE); Cincinnati Stroke Triage Assessment Tool; Prehospital Acute Stroke Severity (PASS); gaze-face-arm-speech-time; Field Assessment Stroke Triage for Emergency Destination; and gaze, facial asymmetry, level of consciousness, extinction/inattention. Main Outcomes and Measures: Planned primary and secondary outcomes were sLAVO and feasibility rates (ie, the proportion of acute stroke codes for which the prehospital scale could be reconstructed). Predictive performance measures included accuracy, sensitivity, specificity, the Youden index, and predictive values. Results: Of 2007 patients who received acute stroke codes (mean [SD] age, 71.1 [14.9] years; 1021 [50.9%] male), 158 (7.9%) had sLAVO. Accuracy of the scales ranged from 0.79 to 0.89, with LAMS and RACE scales yielding the highest scores. Sensitivity of the scales ranged from 38% to 62%, and specificity from 80% to 93%. Scale feasibility rates ranged from 78% to 88%, with the highest rate for the PASS scale. Conclusions and Relevance: This study found that all 7 prediction scales had good accuracy, high specificity, and low sensitivity, with LAMS and RACE being the highest scoring scales. Feasibility rates ranged between 78% and 88% and should be taken into account before implementing a scale.

Stroke patient's alarm choice: General practitioner or emergency medical services.

OBJECTIVES: Stroke patients should be treated as soon as possible since the benefit of reperfusion therapies is highly time-dependent. The proportion of patients eligible for reperfusion therapy is still limited, as many patients do not immediately alarm healthcare providers. The choice of healthcare system entrance influences the time of arrival in the hospital. Therefore, we assessed differences in these choices to obtain insight for strategies to reduce time delays in acute stroke patients. MATERIALS AND METHODS: Patients with suspected acute stroke admitted to the participating hospitals received a questionnaire. We assessed differences between patients who initially alarmed the general practitioner (GP) and patients who directly alarmed the emergency medical services (EMS). Additionally, we assessed regional differences and patient trajectories after medical help was sought. RESULTS: We included 163 patients. Most patients alarmed the GP as primary healthcare provider (n = 104; 64%), and median onset-to-door times were longer in these patients (466 minutes [IQR 149-1586]) compared to patients directly alarming the EMS (n = 59; 36%) (90 minutes [IQR 45-286]). This was even more pronounced in less densely populated areas. Patients who alarmed the GP first, more often had patient delay >15 minutes, hesitated to burden healthcare providers and underestimated symptomatology. CONCLUSIONS: Our results showed that patients who alarmed the GP first instead of the EMS differed in several factors that are potentially modifiable. Strategies to achieve reduction of vital prehospital time delays and to improve patient outcome are optimizing public awareness campaigns and GP triage along with adjusting current guidelines by enabling and focusing on immediate involvement of the EMS once acute stroke is suspected.

Circulating tRNA Fragments as a Novel Biomarker Class to Distinguish Acute Stroke Subtypes.

: Early blood biomarkers to diagnose acute stroke could drastically reduce treatment delays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls.

High Admission Glucose Is Associated With Poor Outcome After Endovascular Treatment for Ischemic Stroke.

BACKGROUND AND PURPOSE: High-serum glucose on admission is a predictor of poor outcome after stroke. We assessed the association between glucose concentrations and clinical outcomes in patients who underwent endovascular treatment. METHODS: From the MR CLEAN Registry, we selected consecutive adult patients with a large vessel occlusion of the anterior circulation who underwent endovascular treatment and for whom admission glucose levels were available. We assessed the association between admission glucose and the modified Rankin Scale score at 90 days, symptomatic intracranial hemorrhage and successful reperfusion rates. Hyperglycemia was defined as admission glucose ≥7.8 mmol/L. We evaluated the association between glucose and modified Rankin Scale using multivariable ordinal logistic regression and assessed whether successful reperfusion (extended Thrombolysis in Cerebral Infarction 2b-3) modified this association. RESULTS: Of 3637 patients in the MR CLEAN Registry, 2908 were included. Median admission glucose concentration was 6.8 mmol/L (interquartile range, 5.9-8.1) and 882 patients (30%) had hyperglycemia. Hyperglycemia on admission was associated with a shift toward worse functional outcome (median modified Rankin Scale score 4 versus 3; adjusted common odds ratio, 1.69 [95% CI, 1.44-1.99]), increased mortality (40% versus 23%; adjusted odds ratio, 1.95 [95% CI, 1.60-2.38]), and an increased risk of symptomatic intracranial hemorrhage (9% versus 5%; adjusted odds ratio, 1.94 [95% CI, 1.41-2.66]) compared with nonhyperglycemic patients. The association between admission glucose levels and poor outcome (modified Rankin Scale score 3-6) was J-shaped. Hyperglycemia was not associated with the rate of successful reperfusion nor did successful reperfusion modify the association between glucose and functional outcome. CONCLUSIONS: Increased admission glucose is associated with poor functional outcome and an increased risk of symptomatic intracranial hemorrhage after endovascular treatment.

Clinical prediction of thrombectomy eligibility: A systematic review and 4-item decision tree.

BACKGROUND: A clinical large anterior vessel occlusion (LAVO)-prediction scale could reduce treatment delays by allocating intra-arterial thrombectomy (IAT)-eligible patients directly to a comprehensive stroke center. AIM: To subtract, validate and compare existing LAVO-prediction scales, and develop a straightforward decision support tool to assess IAT-eligibility. METHODS: We performed a systematic literature search to identify LAVO-prediction scales. Performance was compared in a prospective, multicenter validation cohort of the Dutch acute Stroke study (DUST) by calculating area under the receiver operating curves (AUROC). With group lasso regression analysis, we constructed a prediction model, incorporating patient characteristics next to National Institutes of Health Stroke Scale (NIHSS) items. Finally, we developed a decision tree algorithm based on dichotomized NIHSS items. RESULTS: We identified seven LAVO-prediction scales. From DUST, 1316 patients (35.8% LAVO-rate) from 14 centers were available for validation. FAST-ED and RACE had the highest AUROC (both >0.81, p < 0.01 for comparison with other scales). Group lasso analysis revealed a LAVO-prediction model containing seven NIHSS items (AUROC 0.84). With the GACE (Gaze, facial Asymmetry, level of Consciousness, Extinction/inattention) decision tree, LAVO is predicted (AUROC 0.76) for 61% of patients with assessment of only two dichotomized NIHSS items, and for all patients with four items. CONCLUSION: External validation of seven LAVO-prediction scales showed AUROCs between 0.75 and 0.83. Most scales, however, appear too complex for Emergency Medical Services use with prehospital validation generally lacking. GACE is the first LAVO-prediction scale using a simple decision tree as such increasing feasibility, while maintaining high accuracy. Prehospital prospective validation is planned.

A Reduction in Time with Electronic Monitoring In Stroke (ARTEMIS): study protocol for a randomised multicentre trial.

INTRODUCTION: Time is the most crucial factor limiting efficacy of intravenous thrombolysis (IVT) and intra-arterial thrombectomy (IAT). The delay between alarming the Emergency Medical Services (EMS) dispatch office and IVT/IAT initiation, that is, the 'total system delay' (TSD), depends on logistics and team effort. A promising method to reduce TSD is real-time audio-visual feedback to caregivers involved. With 'A Reduction in Time with Electronic Monitoring in Stroke' (ARTEMIS), we aim to investigate the effect of real-time audio-visual feedback on actual TSD to IVT/IAT to caregivers. METHODS AND ANALYSIS: ARTEMIS is a multiregional, multicentre, randomised open end-point trial including patients ≥18 years considered IVT/IAT-eligible by the EMS dispatch office or on-site EMS personnel. Patients are electronically tracked and randomised for real-time audio-visual feedback on TSD to caregivers via premounted handhelds and tablets throughout the TSD trajectory. Primary outcome is TSD to IVT/IAT. Secondary outcomes comprise proportion of IVT/IAT-treated patients, symptomatic intracerebral haemorrhage, IVT/IAT-treated stroke mimics, clinical outcome after three months and cost-effectiveness. Separate analyses for IAT-patients with or without prior IVT, within or out of office hours and EMS region will be performed. With 75 IAT-patients and 225 IVT-patients in each arm, we will be able to demonstrate a 20 min difference in TSD to IAT and a 10 min difference in TSD to IVT (p=0.05 and power=0.8). ETHICS AND DISSEMINATION: Study findings will be disseminated through peer-reviewed journals and (inter)national conference presentations. TRIAL REGISTRATION NUMBER: NCT02808806; Pre-results.