Correlation between pre-admission blood pressure and outcome in a large telestroke cohort

Journal of Clinical Neuroscience 62 (2019) 33–37

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Clinical study

Correlation between pre-admission blood pressure and outcome in a large telestroke cohort Ahmad Sweid a, Elias Atallah a, Hassan Saad c, Kimon Bekelis a, Nohra Chalouhi a, Sophia Dang a, Jonathan Li a, Ayan Kumar a, Justin Turpin a, Randa Barsoom a, Stavropoula Tjoumakaris a, David Hasan b, Maureen DePrince a, Giuliana Labella a, Robert H. Rosenwasser a, Pascal Jabbour a,⇑ a

Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, PA, United States Department of Neurological Surgery, University of Iowa, Department of Neurosurgery, Iowa City, IA, United States c Department of Neurological Surgery, Arkansas Neurosciences Institute, Little Rock, AR, United States b

a r t i c l e

i n f o

Article history: Received 28 August 2018 Accepted 3 January 2019

Keywords: Telestroke Acute ischemic stroke Cerebrovascular accident Mechanical thrombectomy Blood pressure monitoring Thrombolysis

a b s t r a c t Background: Telemedicine rapidly connects patients, with acute ischemic stroke symptoms, with neurovascular specialists for assessment to reduce chemical thrombolysis delivery times. Management of AIS includes maintaining target systolic blood pressures (SBP). In this retrospective study, we assess the efficacy of the telestroke (TS) system at a primary stroke center and the prognostic value of SBP throughout the transportation process. Methods: Patients presenting with acute-onset neurological symptoms to the TS hospitals network, over a 5-year period, were assessed. Those with a confirmed diagnosis of AIS were included. We examined demographics, presenting-NIHSS, last SBP before transfer from the network hospital and continuous BP during transport, stroke risk factors, hospital-course, door-to-needle (DTN) time, treatments, and modified Rankin Scale(mRS). Multivariate analysis was conducted to evaluate the prognostic value of SBP on stroke outcome. Results: Of 2,928 patients identified, 1,353 were diagnosed with AIS. Mean age was 66.6 years (SD = 15.4), 47.6% female. Most cases affected the MCA(44.5%). Mean presenting-NIHSS was 8.67(SD = 8.38) and mean SBP was 148 mmHg(SD = 25.39). 73.2% treated using a standard protocol, 23.7% given IVrt-PA, and 6.8% received mechanical thrombectomy(MT). Mean DTN was 96 min(SD = 46; 27.3% <60 min). Age, presenting-NIHSS and pre-existing hypertension were associated with higher mortality and/or higher mRS. SBP was not associated with higher mortality and morbidity. Conclusions: This study displays better clinical outcomes at latest follow-up when compared to current international TS studies. SBP during transportation to the hub hospital did not prove to be a useful prognostic metric. However, future studies should address the limitations of this study to confirm these findings. Ó 2019 Elsevier Ltd. All rights reserved.

1. Introduction

⇑ Corresponding author at: Neurological Surgery, Chief Division of Neurovascular Surgery and Endovascular Neurosurgery, Thomas Jefferson University Hospital, 901 Walnut street 3rd Floor, Philadelphia, PA 19107, United States. E-mail addresses: [email protected] (A. Sweid), [email protected] (E. Atallah), [email protected] (N. Chalouhi), Sophia.dang@ jefferson.edu (S. Dang), [email protected] (J. Li), [email protected] (A. Kumar), [email protected] (J. Turpin), [email protected] (R. Barsoom), [email protected] (S. Tjoumakaris), david-hasan @uiowa.edu (D. Hasan), [email protected] (M. DePrince), [email protected] (G. Labella), [email protected] (R.H. Rosenwasser), [email protected] (P. Jabbour). https://doi.org/10.1016/j.jocn.2019.01.014 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.

In the United States, stroke is a prominent, fatal disease and a leading cause of disability [1,2]. Neurological deficits resulting from tissue infarct are remediable, only if identified and treated quickly [1]. IV Recombinant Tissue-Plasminogen Activator (IVrtPA) is the quintessential FDA-approved drug administered during the acute phase of ischemic strokes (IS) to try to restore blood flow and prevent a completed infarct. Since only 55% of Americans live within 60 miles of a primary stroke center, introduction of TS units has proven effective in reducing permanent neurologic sequelae by improving treatment delivery times through tele-consults with neurovascular specialists experienced in the medical and surgical

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treatment of AIS [3,4]. Several studies support the importance of cost-effective practice-based telemedicine systems with increased utilization by dedicated international stroke centers [4–8]. Their success has been attributed to clear and proficient communication, professional staff with extensive expertise, and quality reinforcement [5]. Nevertheless, delayed videoconferencing, reduced response time, and physician burnout are shown to decrease TS efficacy [5,6]. In addition to rapid TS assessment and IVrt-PA treatment, SBP above 140 mmHg is generally targeted in the management of AIS as SBP below this threshold has been shown to be independently predictive of poor neurologic outcome [9]. Therefore, monitoring basic vital signs and maintenance of SBP through IV-fluid resuscitation during emergency medical services (EMS) transportation proves indispensable and should be of significant concern during AIS. We analyzed all patients with AIS symptoms transported to our institution, via EMS ground vehicles or helicopters, to verify the usefulness and efficiency of the TS system and the prognostic value of vital signs monitoring throughout the transportation process. 2. Methods 2.1. Cohort Between March 2011 and June 2016, 2928 patients manifesting symptomatology of AIS received teleconsultation from our specialized TS unit which serves over 40 regional medical institutions within the Pennsylvania & New Jersey Area. Patients were transported directly from an outside hospital via EMS ambulance or helicopter to our institution, a comprehensive stroke center and a hub hospital for telemedicine. The study protocol was reviewed and approved by the Institutional Review Board. Patients’ consent was not obtained due to the retrospective nature of the study. 2.2. Study protocol Heart rate (HR) and rhythm, blood pressure (BP) and mean arterial pressure (MAP) were collected upon initial presentation of the patient to the spoke hospital, during transportation and at the arrival to our center (Table 1). All patients were assessed by a neurovascular specialist through telemedicine to determine if they are candidates for IVrt-PA. If administered, patients received IVrtPA before transportation. Neurological disability was assessed with the National Institutes of Health Stroke Scale (NIHSS) before transportation and on arrival to the hub hospital. Stroke territory was determined based on imaging. Patients were divided into two groups according to their management plan: the first received medical treatment and/or IVrt-PA and the second regrouped patients received mechanical thrombectomy (MT). At our center, patients with NIHSS > 6 systemically received a Computed Tomography Angiography-Perfusion (CTA-CTP) as a screening tool for MT. The neurovascular surgeon on-staff performed the endovascular

Table 1 Mean blood pressure values before transportation, during transportation and at arrival to the institution.

* y à

Mean

Before Transportation (mmHg)

During Transportation (mmHg)

At Arrival to the Institution (mmHg)

SBP* DBPy MAPà

148.4 81.3 103.3

148.5 81.6 103.0

144.8 80.3 101.37

Systolic Blood Pressure, Diastolic Blood Pressure, Mean Arterial Pressure.

MT. The large vessel recanalization rate was assessed with the Thrombolysis in Cerebral Infarction (TICI) scale by the performing attending and registered nurse at the end of each procedure. 2.3. Outcome variables The primary outcome of this study was the impact of SBP variations during tele-transportation on the long-term clinical outcome (mRS before discharge and at each follow-up visit) and mortality rate. SBP was obtained from outpatient databases (EMS-charts). The secondary outcome was to assess the number of patients who received MT and/or IVrt-PA after receiving TS consultation. 2.4. Patient follow-up Whether they received IVrt-PA or underwent MT, patients were followed by the on-duty physician that made the teleconsultation on the day of admission: (72.4%) were managed by neurologists and (27.6%) were followed by neurovascular surgeons. After admission, the patient’s clinical status was periodically assessed for any neurological worsening, NIHSS was recalculated and compared to initial values. Subjects routinely received diagnostic and follow-up CT-Scan and Magnetic Resonance Imaging in order to evaluate the progression of ischemic cerebral tissue. Results were reviewed by the corresponding physician and an independent radiologist for any subsequent ischemic event or hemorrhagic conversion. mRS was recorded at discharge and each outpatient follow-up. 2.5. Exposure variables The association of outcome with relevant exposure variables was evaluated in a multivariate analysis. The primary exposure variable was the BP values (SBP and MAP) upon arrival to spoke hospital, during transportation and upon arrival at our institution. As well as binary BP values <140 mmHg and >185 mmHg. 2.6. Covariates and comorbidities Covariates used for risk adjustment were age and gender. Comorbidities used for risk adjustment were: hypertension, diabetes, smoking, MT, TICI score, recanalization device, IVrt-PA, NIHSS before treatment. 2.7. Statistical analysis To investigate the association of BP and our outcome measures, we used several methods to address confounding variables. Initially, for binary outcomes, we used a multivariable logistic regression controlling for the covariates mentioned above. In order to control for clustering at the physician level, we employed mixed-effect models with a physician as a random effects variable. For continuous outcomes, we used the corresponding linear regression analyses. In an alternate way to control for confounding for binary outcomes, we employed a propensity score-adjusted logistic regression model. To derive the propensity of achieving our primary exposure variables, we developed a prediction model using logistic regression, based on all the covariates described above. We subsequently employed a logistic regression with adjustment (stratification) by quantiles (we chose the number of quantiles to be 10) of the propensity score. Operating physician was again used as a random effects variable. Patients who were lost to follow-up were not included in the original analysis. In a sensitivity analysis, all the above analyses were repeated using multiple imputations for patients lost to follow-up. We created five imputed datasets. The directions of

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observed associations did not change, and these results are not reported further. Regression diagnostics were performed for all analyses. Given that our study had a sample of 1354 patients, we had an 80% power to detect a difference in mortality as small as 7.6%, at an a-level of 0.05. All probability values were the result of two-sided tests. Stata version 13 (StataCorp, College Station, TX) was used for statistical analysis.

Table 2 Association between outcomes and blood pressure measurements.

SBP1* MAP1y SBP2 MAP2

3. Results

SBP3

3.1. Demographic characteristics Between March 2011 and June 2016, 2928 patients with acuteonset neurological symptoms received a TS consultation through our experts on call. 1353 were admitted with a diagnosis of AIS. Patients were referred from >40 regional facilities to our hub hospital. The mean of age was 66.6 years (SD = 15.4 years; Min = 16, Max = 111) with 47.6% female (644/1353). 39.9% were transferred via helicopter and 60.1% via ambulance. 990 (73.2%; mean = 0.61, SD = 0.49) patients were treated conservatively with standard medical protocol, 322(23.7%) patients were dispensed IVrt-PA, and 93(6.8%) of the patients received MT. Stroke territories were the following: 75% affecting the anterior circulation and 25% affecting the posterior circulation. The mean NIHSS recorded before any intervention and upon arrival of medical staff to patients’ homes was 8.67 (SD = 8.38; Min = 0, Max = 38). HR was collected during transportation: normal sinus rhythm (74%), atrial fibrillation (13.2%), sinus bradycardia (5.3%), sinus tachycardia (6.1%), atrioventricular block (0.9%). 3.1.1. Mechanical thrombectomy The proportion of patients who received thrombectomy was 7% (93/1353). The average TICI scale registered at the end of each thrombectomy was 2.99 (SD = 1.62; Min = 0, Max = 3): 1 (4.3%), 2a (0%), 2b (9.7%) and 3 (85.6%). 92 patients (98%; mean = 0.06, SD = 0.27) were treated with the Solitaire Ò Flow Restoration Device (Covidien). The mean mortality rate in the MT group was 0.17 (SD = 0.97). The average mRS at the latest follow-up visit, reflecting patients’ functional status, was 2.90 (SD = 1.66; 37.6%  2) and average NIHSS for the same group was 12.8 (SD = 7.88; Min = 0, Max = 32). 3.1.2. Medical treatment and IVrt-PA chemical thrombolysis 49.5% (46/93) treated with an MT were pretreated with IVrt-PA. 27% (273/990) patients who received medical treatment were treated with a concomitant IVrt-PA. The average DTN-time was 96 min (SD = 46; Min = 0, Max = 200; 27.3% < 60 min). The mean mortality rate in the group that did not receive an MT was 0.10(SD = 0.40). The average mRS at latest follow-up visit was 2.11(SD = 2.02; 60.7%  2) and average NIHSS for the same group was 8.37 (SD = 8.33; Min = 0, Max = 38). 3.2. Vital signs associations with clinical outcomes In the global population, mean MAP1 (before transportation) was 103.4 mmHg (SD = 16.51) and mean SBP1 (before transportation) was 148.39 mmHg (SD = 25.39). In a multivariate mixedeffects logistic regression, SBP1 (OR 0.99; CI95%, 0.98–1.01; p = 0.41) and MAP1 (OR 0.98; CI95%, 0.97–1.00; p = 0.09) were not associated with higher mortality rate. Similarly, SBP1 (OR 0.007; CI95%, 0.004–0.003; p = 0.71) and MAP1 (OR 0.002; CI95%, 0.01–0.004; p = 0.56) were not associated with latest mRS. In the global population, mean MAP2 (during transportation) was 103.02 mmHg (SD = 18.36) and mean SBP2 (during transporta-

MAP3 * y

Mortality OR (CI95%) p value

mRS OR (CI95%) p value

0.99(0.98–1.01) 0.41 0.98(0.97–1.00) 0.09 0.99(0.98–1.00) 0.24 0.99(0.98–1.01) 0.28 0.99(0.98–1.01) 0.61 0.99(0.98–1.00) 0.18

0.007(0.004–0.003) 0.71 0.002(0.01–0.004) 0.56 0.00(0.004–0.003) 0.84 0.00(0.01–0.005) 0.89 0.00(0.002–0.004) 0.61 0.002(0.0051–0.0053) 0.96

Systolic Blood Pressure, Mean Arterial Pressure.

tion) was 148.51 mmHg (SD = 26.50). In a multivariate mixedeffects logistic regression, SBP2 (OR 0.99; CI95%, 0.98–1.00; p = 0.24) and MAP2 (OR 0.99; CI 95%, 0.98–1.01; p = 0.28) were not associated with higher mortality rate. Similarly, SBP2 (OR 0.00; CI95%, 0.004–0.003; p = 0.84) and MAP2 (OR 0.00; CI95%, 0.01–0.005; p = 0.89) were not associated with latest mRS. In the global population, mean MAP3 (at destination facility) was 101.3 mmHg (SD = 17.37) and mean SBP3 (at destination facility) was 145.3 mmHg (SD = 24.36). In a multivariate mixed-effects logistic regression, SBP3 (OR 0.99; CI95%, 0.98–1.01; p = 0.61) and MAP3 (OR 0.99; CI95%, 0.98–1.00; p = 0.18), were not associated with higher mortality rate. Similarly, SBP3 (OR 0.00; CI95%, 0.002–0.004; p = 0.61) and MAP3 (OR 0.002; CI95%, 0.0051– 0.0053; p = 0.96) were not associated with latest mRS (Table 2). 54.5% (30/55) patients of those who had an SBP2 > 185 mmHg had an mRS  2. In the same group, mean NIHSS before any intervention was 8.41 (SD = 7.03). Among the SBP2 patients with SBP2 > 185 mmHg, 16.4% (9/55) patients were dispensed IVrt-PA, and 1.8% (1/55) patient received MT. 59% (485/820) of patients with 140 mmHg  SBP2  185 mmHg had an mRS  2. In the same group, mean NIHSS before any intervention was 8.53 (SD = 8.40), 22% (181/820) were administered IVrt-PA, and 5.7% (47/820) patients received MT 61.7% (415/672) of patients with SBP2 < 140 mmHg had an mRS  2. In the same group, mean NIHSS before any intervention was 8.41 (SD = 8.65), 22.3% (150/672) received rt-PA and 8.1% (55/672) (Table 2). In a multivariable mixed-effect logistic regression, SBP < 140 mmHg was not correlated with mRS on latest followup (OR 1.167; CI95%, 0.04 to 0.96; p = 0.422) nor with higher mortality rate (OR, 1.167; CI95%, 0.21–6.38; p = 0.858). 140 < SBP  185 mmHg was not correlated with mRS on latest follow-up (OR 0.29; CI95%, 0.38 to 0.96; p = 0.397) nor with higher mortality rate (OR 0.89; CI95%, 0.52–1.55; p = 0.705). SBP > 185 mmHg was not correlated with mRS on latest followup (OR 0.28; CI95%, 0.39 to 0.97; p = 0.410) nor with higher mortality rate (OR 0.98; CI95%, 0.610–1.58; p = 0.945). All the multivariate mixed-effects logistic regressions showed an association between increasing age (p = 0.001), NIHSS (p = 0.000) and pre-existing hypertension(p = 0.027) and higher mortality rate. Only increasing age (p = 0.000) and NIHSS (p = 0.001) were additionally associated with mRS score on the latest follow-up. 37.6% of patients receiving MT and 60.7% in the other group had mRS  2. 4. Discussion Hypertension is an established modifiable risk factor for stroke [10]. In the context of AIS, elevated BPs are associated with the

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development of cerebral edema and hemorrhagic transformation [11]. Despite these findings, long-standing controversy persists regarding the relationship between SBP and clinical outcome in AIS with reported findings varying between poor prognosis to no association [12–17]. It would seem beneficial to maintain a relatively high BP in the management of AIS; low BPs during the acute phase of AIS are associated with poor long-term outcomes and increased 90-day mortality [18–20]. Widely fluctuating BP during this time also appears to be associated with an increased risk of death at 90 days [19–21]. In the present study, we did not observe any statistical association between SBP fluctuation and long-term clinical outcome among our patient cohort. Although the average SBP of patients before, during and after transportation to the referring hospitals were relatively constant and within recommended ranges, they did not reflect the individual BP of every patient. For this reason, we divided our cohort into three groups according to their poststroke, pre-treatment SBPs for comparative analysis. Cutoffs were designated to be at 140 mmHg and 185 mmHg. A SBP > 140 mmHg is targeted to prevent hypotension, especially if they are candidates for IVrt-PA or MT [9]. A SBP < 185 mmHg is a determinant of IVrt-PA thrombolysis eligibility [22]. Further support for these designations comes from the International Stroke Trial which observed a U-shaped relationship between baseline SBP and early/late mortality, with poor outcomes tending to be more pronounced outside the 140–180 mmHg SBP range. Binary statistical comparison of a good clinical outcome, defined as mRS  2, between patients who had a SBP < 140, between 140–185 and >185 mmHg did not show any significant difference. Two very recent pilot studies have addressed the association between SBP measurements and clinical outcome in Traumatic Brain Injury (TBI) and intracerebral hemorrhage (ICH). Spaite et al. studied the association of SBP and risk of mortality in patients with TBI over a wide range of measurements (40–119 mmHg). They found a linear monotonically decreasing association between SBP and the severity-adjusted probability of mortality. Each 10points increase in SBP was associated with a decrease of 18.8% in the adjusted odds of death without any identifiable threshold between 40 and 119 mmHg. In their discussion, they questioned the previously set concept of SBP cutoff of 90 mmHg below which brain damage was believed to occur [17,23]. Another prospective, randomized, assessor-blinded trial was conducted by Zheng et al. investigating the safety of intensive BP control in surgical patients with spontaneous ICH. Patients were either allocated to intensive BP lowering group where SBP was maintained between 120 and140 mmHg or to a conservative group, where the target perioperative SBP was maintained between 140 and 180 mmHg. They did not detect a significant difference in re-hemorrhage rate between the two groups and concluded that perioperative intensive SBP control was not associated with a decrease in re-hemorrhage rate in patients with spontaneous ICH [24]. Our present study is not the first one to find no association between SBP during the acute phase of IS and clinical outcome; however, it included the most substantial number of patients. Although the pathophysiology of TBI, ICH, and AIS differs a lot, we believe there is a common ground between our observation and the results presented in the studies as mentioned earlier. The cutoff SBP values used in neuropathological processes are not supported by reliable evidence and are extrapolated from cardiac literature. Well-controlled BP is essential for adequate management of patients presenting with AIS, especially among those eligible for IVrt-PA administration. For example, in a population-based study by Kleindorfer et. al, 10% of patients who qualified for IVrt-PA treatment did not receive IVrt-PA because of severe hypertension [25]. Less than one-third of patients treated with IVrt-PA were present within the recommended 60 min of DTN, therefore management

of elevated BP in a timely fashion is pivotal [26]. Among our cohort, 16.4% with a BP > 185 mmHg received IVrt-PA. We do not know how many patients were excluded from IVrt-PA thrombolysis solely due to BP measurement considerations. Around 22% of our patients who had SBP < 185 mmHg received IVrt-PA. Thus, many patients did not get IVrt-PA for reasons not exclusive to SBP. At this point, we could not dissect our data any further. However, we still advocate for SBP lowering to less than 185 mmHg as soon as possible to increase IVrt-PA eligibility rates. More definitive results will hopefully be obtained from the ongoing Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) trial [27]. Another interesting finding in our study is the recruitment of new stroke patients eligible for MT through the TS network. Around 7% (93/1353) received MT, half of whom were already treated with IVrt-PA. A meta-analysis done by Badhiwala et al. found the proportion of patients attaining functional independence was markedly more significant in those who underwent MT after IVrt-PA administration [28]. 38% of MT patients had an mRS  2 on their last follow-up visit with only 7% (7/93) of stroke-related deaths. Many clinical trials have also demonstrated the benefit of MT done alone or after IVrt-PA. A subgroup analysis of these trials showed that patients who received combined therapy or had MT done within six hours, among other factors, had a significantly better functional outcome [28]. Accordingly, we believe that implementing new strategies and a multidisciplinary approach to stroke patients leads to better results. One way to do so is by improving the TS service, so patients eligible for IVrt-PA receive it as soon as possible, and then transfer should be initiated to a comprehensive stroke center; ‘‘ship and drip” model.

5. Limitations While our series is the largest-to-date in studying possible associations between blood pressure values with patients’ clinical outcome and mortality rate, our study design is limited by the retrospective aspect of the data collection. The cutoff values defining the SBP range (140–185 mmHg) used in this study might be narrow compared to other ranges (100–200 mmHg) used in different studies in correlating BP variations to mortality rate. To our knowledge, our study could be contemplated as a pilot study regrouping the most significant number of TS patients with AIS symptoms, referred to a single institution, receiving IVrt-PA and MT. Nonetheless, more studies should be conducted to reduce controversies concerning the effect of SBP fluctuations on AIS patients, especially among the different subtypes of strokes where outcomes depend on various factors other than BP values. These stroke subtypes, based on topographical anatomy and vessel size, may respond differently to BP fluctuations; it seems judicious to control this feature in future analysis of BP data.

6. Conclusion More patients manifesting with AIS symptoms are receiving rapid medical care due to expanding networks of specialized TS units. Although no significant association was found between SBP fluctuations during transportation and clinical outcome (mRS and/or mortality rate), further studies are needed to look at different aspects of this association.

Acknowledgements None.

A. Sweid et al. / Journal of Clinical Neuroscience 62 (2019) 33–37

Disclosure This research received no specific grant from any funding agency in public, commercial or not-for-profit sectors. All authors have read and approved the submitted manuscript; the manuscript has not been submitted elsewhere nor published elsewhere in whole or in part. COI statement The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Subject terms Cerebrovascular Disease/Stroke, Cerebrovascular Procedures, Blood Pressure, Hypertension, High Blood Pressure References [1] Madhavan M, Karceski S. Telestroke: Is it safe and effective? Neurology 2016;87(13):e145–148. [2] Legris N, Hervieu-Begue M, Daubail B, et al. Telemedicine for the acute management of stroke in Burgundy, France: an evaluation of effectiveness and safety. Eur J Neurol 2016;23(9):1433–40. [3] Chalouhi N, Dressler JA, Kunkel ES, et al. Intravenous tissue plasminogen activator administration in community hospitals facilitated by telestroke service. Neurosurgery 2013;73(4):667–71. discussion 671–662. [4] Akbik F, Hirsch JA, Chandra RV, et al. Telestroke-the promise and the challenge. Part two-expansion and horizons. J Neurointerv Surg 2016. [5] Sanders KA, Patel R, Kiely JM, Gwynn MW, Johnston LH. Improving telestroke treatment times in an expanding network of hospitals. J Stroke Cerebrovasc Dis 2016;25(2):288–91. [6] Richard S, Mione G, Varoqui C, et al. Simulation training for emergency teams to manage acute ischemic stroke by telemedicine. Medicine (Baltimore) 2016;95(24):e3924. [7] Yaghi S, Hinduja A, Bianchi N. Predictors of major improvement after intravenous thrombolysis in acute ischemic stroke. Int J Neurosci 2016;126 (1):67–9. [8] Akbik F, Hirsch JA, Chandra RV, et al. Telestroke-the promise and the challenge. Part one: growth and current practice. J Neurointerv Surg 2016. [9] Bowry R, Navalkele DD, Gonzales NR. Blood pressure management in stroke: five new things. Neurol Clin Pract 2014;4(5):419–26. [10] Gilmore RM, Miller SJ, Stead LG. Severe hypertension in the emergency department patient. Emerg Med Clin North Am 2005;23(4):1141–58.

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