Thrombolytic Therapy

Patients who were at least 18 years of age were enrolled if they could undergo randomization within 12 hours after having an acute ischemic stroke with a score of 3 or less on the National Institutes of Health Stroke Scale (NIHSS) (scores range from 0 to 42, with higher scores indicating greater stroke severity) or a high-risk TIA with a score of 4 or more on the ABCD^{2 (link)} scale¹⁴ (which estimates the risk of recurrent stroke after a TIA on the basis of age, blood pressure, clinical features, duration of symptoms, and presence of diabetes; scores ranges from 0 to 7, with higher scores indicating a greater risk of stroke). They were also required to undergo computed tomography or magnetic resonance imaging to rule out intracranial bleeding or other conditions that could explain the neurologic symptoms or detect any contraindications to a trial treatment. Patients with TIA and minor, nondisabling ischemic stroke are generally not considered to be candidates for thrombolysis or endovascular therapy.^{10 (link)} Additional details regarding the inclusion and exclusion criteria are provided in the protocol.^{13 (link)}Patients were ineligible if the symptoms of the initial TIA were limited to isolated numbness, isolated visual changes, or isolated dizziness or vertigo or if they had received any thrombolytic therapy within 1 week before the event. Patients were also ineligible if they were candidates for thrombolysis, endovascular therapy, or endarterectomy; had planned use of antiplatelet therapy or anticoagulation therapy (including those with presumed atrial fibrillation or cardiovascular disease, in whom anticoagulation would be indicated); had a contraindication to aspirin or clopidogrel; or had anticipated use of a nonsteroidal antiinflammatory drug for more than 7 days during the trial period. Written informed consent was required before the performance of any trial procedure.

The project started with development of an 8-question survey tool (online Appendix A) via a multi-disciplinary expert consensus process. Four pairs of questions focused on the following attributes: EMS devices and destination protocols, the designation of certain percutaneous coronary intervention (PCI) hospitals as STEMI Receiving Centers (SRC), inter-hospital transfer protocols for non-PCI Referral Hospitals, and the region’s quality improvement (QI) process. The degree of utilization for each variable was assessed by a multiple-choice format for each LEMSA region: A- none (0%), B- some (<50%), C-most (50–94%), D- all (≥95%), and E- unknown. The duration was evaluated by asking participants for the calendar year that choice C or D was true for each of the eight questions.
Next, the 8-question survey tool was distributed at the annual meeting of administrators and medical directors of California LEMSAs to get responses valid through December, 2014. Incomplete or inconsistent survey response received email follow-up for clarification by the study coordinator. Published ranking will be de-identified, but each LEMSA will confidentially receive their scores.
The first scoring approach was the Total Regionalization Score (TRS). Points were assigned for each selected answer in the survey (A = 0 points, B = 1 point, C = 2 points, D = 3 points) and multiplied by the number of years that each choice was True. This calculation was repeated for all eight questions in the survey and summed to yield the TRS for each LEMSA. The 33 LEMSAs were then ranked from highest to lowest TRS on an Excel spreadsheet.
An example of TRS calculations comes from a hypothetical region that first equipped at least 50% of its paramedic units with PH-ECG devices in the year 2010, and then was able to equip all their ambulances in 2011. Thus, the “C” choice in 2010 would equal 2 points (2 points × 1 year) and a “D” choice from 2011–2014 would equal 12 points (3 points × 4 years), resulting in 14 total points for Question #1. Repeat these steps for Questions #2 to #8 and sum to find the TRS for this hypothetical LEMSA.
The second approach was called the Core Score, and it focused on only 4 survey questions by assuming that the designation of STEMI Receiving Centers must have occurred at the beginning of any LEMSA’s regionalization effort. The Core Score then evaluated the evolution of either pre-hospital or inter-hospital networks as a spectrum: None, Partial, Substantial, or Complete and scored as 0, 1, 2, and 3 points, respectively, for each year that a given threshold was achieved. Core elements of any pre-hospital (PH) network are the presence of PH-ECG devices and Destination Protocols to the SRC (survey Questions 1 and 2). Similarly, inter-hospital transfer primarily depends on identifying the two types of non-PCI hospitals: Type 1 Referral Hospitals are urban/suburban and transfer directly to an SRC for primary PCI (Question 5), whereas Type 2 Referral Hospitals are too far away (rural/remote) to meet guideline-based PCI metrics and need to provide pre-transfer Fibrinolytics to eligible patients (Question 6).
With the Core Score, partial regionalization was defined as the occurrence of “C” status for either pre-hospital (both Questions #1 and #2) or inter-hospital survey items (either Questions #5 or #6), whereas Substantial regionalization occurred in the calendar year that “C” applied for both pre-hospital and inter-hospital questions. Complete regionalization in LEMSA occurred in the calendar year that “D” (≥95%) was selected both for Questions #1 and #2, as well as the highest choice from either Question #5 or #6.
A Core Score calculation example comes from the following hypothetical region. In 2008, this region equipped more than 50% of the ambulances with PH-ECG devices and simultaneously instituted destination protocols. Next, in 2010, it got most Referral hospitals transferring to their nearest SRC, and then in 2012 got all (≥95%) of the EMS vehicles fully equipped and all of their Referral Hospitals transferring. This scenario would be quantified as follows: Two years (2008–09) of Partial regionalization would yield 2 points, two years (2010–2011) of Substantial regionalization would yield 4 points, and three years (2012–2014) of Complete regionalization would yield 9 points, for a total Core Score of 15 points.