Open Access Open Badges Research article

Provider perceptions of barriers to the emergency use of tPA for Acute Ischemic Stroke: A qualitative study

William J Meurer12*, Jennifer J Majersik3, Shirley M Frederiksen1, Allison M Kade1, Annette M Sandretto1 and Phillip A Scott1

Author Affiliations

1 Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA

2 Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA

3 Department of Neurology, University of Utah, Salt Lake City, Utah, USA

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BMC Emergency Medicine 2011, 11:5  doi:10.1186/1471-227X-11-5

The electronic version of this article is the complete one and can be found online at:

Received:19 October 2010
Accepted:6 May 2011
Published:6 May 2011

© 2011 Meurer et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care.


Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist).


The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines.


Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful.

Trial Registration identifier: NCT00349479


Ischemic stroke is a devastating disease, affecting approximately 600,000 adults in the U.S. every year, leaving many survivors with significant functional limitations[1]. Intravenous administration of tissue plasminogen activator (tPA) is recommended by American Heart Association (AHA) guidelines for the early treatment of acute ischemic stroke[2,3]. However, only 1% to 3% of all ischemic stroke patients in community settings receive thrombolytic therapy; this is estimated to be about half of those eligible[4,5]. This low rate suggests numerous barriers exist at both the provider and institutional levels[6].

A large proportion of patients are excluded from treatment due to factors outside of physician control, such as delayed presentation to the hospital. In spite of this, provider-specific barriers remain a significant determinant of low treatment rates[4,6]. Previously it has been shown that professional education can improve treatment rates in stroke[7]. However, for the educational effort to be successful it is critical that the effort is tailored to the targeted populations of providers[8].

The INcreasing Stroke Treatment through INterventional behavioral Change Tactics (INSTINCT) trial is a cluster randomized, controlled trial aimed at increasing appropriate tPA use in ischemic stroke by first determining hospital-specific barriers and then providing targeted, professional educational interventions. Barriers were determined using a partial grounded theory method, whereby qualitative data obtained through focus group discussions is coded into themes using a previously-described taxonomy[9]. Qualitative methods are uniquely suited to develop understanding of complex situations that are difficult to measure quantitatively[10]. The milieu of clinician attitudes, institutional practices, and hospital resources involved in emergency stroke care in the community is a prime example of such a setting for which qualitative methods may provide important insights. Our primary objective was to describe the qualitatively-derived barriers to clinician compliance with guidelines recommending the use of tPA in appropriate patients as discovered in the barrier assessment phase of INSTINCT.


Ethics Statement

The protocol was approved by the University of Michigan Institutional Review Board (IRBMED) and all relevant site IRBs. Written informed consent was obtained from all participants in focus groups and interviews.

INSTINCT Trial Overview

The INSTINCT trial is evaluating the hypothesis that initial barrier assessment focused on tPA use in stroke followed by targeted, interactive educational interventions will increase appropriate tPA use[11]. These educational initiatives were planned to be specifically tailored to the needs of each site. A schematic of the INSTINCT trial is depicted in Figure 1. After site selection and randomization, an initial period of barrier assessment was conducted which involved focus groups, interviews, and surveys. The results of the barrier assessments were then used to tailor site-specific continuing medical education (CME) lectures to the most important barriers that participants reported. Additional interventions to improve stroke care occurred concurrently and included assistance with clinical protocol development, 24-7 telephone access to the University of Michigan acute stroke team, mock stroke codes, and targeted messaging. Examples of targeted messaging include informing participants of their site's progress and the overall performance of other sites within INSTINCT and critical incident debriefing, where a physician from the clinical coordinating center contacted local physicians to discuss specific instances of deviations from American Stroke Association guidelines or treatment complications. Appropriate use of tPA and total number of stroke patients were tracked at each hospital throughout the study period and served as the primary method by which the INSTINCT intervention was measured. Finally, the INSTINCT trial required the recruitment of a local stroke champion at each site to serve as the local principal investigator and to act as a liaison between the INSTINCT trial clinical coordinating center and the health care providers at each site.

thumbnailFigure 1. Overview of INSTINCT trial. Process of barrier assessments and interventions at INSTINCT hospitals.

Study Setting

Twenty-four hospitals were randomly selected from the population of Michigan acute care hospitals and matched into 12 pairs based on emergency department volume and number of stroke patients (See Figure 1). Hospitals that were established academic comprehensive stroke centers were excluded. Primary stroke centers were not excluded, but were relatively uncommon in the hospital sample at the time of randomization. Each pair contained an intervention site and a control site, randomly assigned. Intervention group hospitals were 25% urban with a total aggregate annual emergency department volume of 397,193 in 2007.

Rationale for qualitative inquiry

An overall goal of the qualitative inquiry was to design a process which would complement existing quality improvement programs, such as Get With the Guidelines (GWTG)- Stroke[12]. While GWTG-Stroke provides important tools for measuring progress, it is limited in its specific ability to encourage clinicians to comply with guidelines recommending intravenous tPA to eligible stroke patients. This is of particular importance in the United States, where emergency physicians (EPs) are typically the frontline of acute stroke care. In most U.S. practice settings, immediate access to a neurologist or stroke specialist does not exist[13]. Many decisions regarding stroke treatment, up to and including thrombolytic use, are made by EPs. Even in settings with access to acute stroke teams, the emergency care providers (physicians and nurses) need to recognize that the patient is having a stroke and alert the stroke team. In both instances, clinician beliefs about the relative efficacy of stroke thrombolysis, physician expertise, past experience, and concern about adverse effects influence the efficiency and overall tone of the decision-making process. Thus, the initial relationship at the bedside between clinician and decision maker (patient or family member) considering thrombolysis for stroke is both complex and ill-defined[14]. In a large proportion of community hospitals in the United States this role is most commonly filled by EPs.

Overview of data collection process

The qualitative data collection and analysis methods have been described in detail previously and are summarized below[15]. During design, data collection, and analysis, we adhered to the consolidated criteria for reporting qualitative research (COREQ) when possible as outlined in Table 1[16]. The qualitative inquiry occurred in two phases. Phase 1 consisted of exploratory focus groups that were conducted at a central meeting of stroke champions and stakeholders from each of the intervention sites; the results of these discussions were used to refine discussion guides for phase 2. During the phase 2 barrier assessment process, both focus groups and one-on-one interviews were conducted by the INSTINCT trial team at each of the 12 intervention hospitals.

Table 1. COREQ Checklist


Characteristics of participants

There were 30 participants in the six initial focus groups (phase 1): 10 EPs, 15 nurses, 3 neurologists, 1 hospitalist, and 1 pharmacist. Focus group composition during phase 1 was mixed by site and occupation and the groups ran concurrently. In phase 2, two focus groups were conducted at each of the 12 intervention sites, one of EPs and one of primarily emergency department nursing staff. A total of 55 EPs and 48 nurses participated in phase 2 focus groups. Additionally, one-on-one structured interviews were conducted with a neurologist, an administrator, and a radiologist at each intervention site. Focus group participants were recruited by the local principal investigator from each site. Participants with disparate opinions and past experience were sought to enhance the diversity of responses. The demographics of these participants were not collected to protect anonymity.

Data Acquisition

The focus group discussion guide was developed with a professional focus group consultant. It is included in Additional file 1 (appendix_focus_group_script.doc). All focus groups and interviews were digitally recorded and transcribed verbatim.

Additional file 1. This is the final focus group script that was used for emergency physician or nurse focus groups.

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Thematic Analysis

A pre-specified taxonomy was employed to characterize major barriers to clinical guideline adherence[9]. Barriers were broadly characterized as internal or external. External barriers were defined to describe issues inhibiting guideline adherence outside the direct control of physicians. Internal barriers were defined as those barriers that are directly related to individual physician knowledge and attitudes. Two investigators (JJM, WJM) independently coded the transcripts into themes using NVIVO 7 software (QSR International). The coding guide is presented in Table 2, with the comprehensive coding guide used by the investigators provided in Additional File 2 (Appendix_coding_guide_v1.3.doc). The pre-specified major themes were utilized to optimize the process by which the major barriers were categorized and ranked to prioritize the CME educational interventions at each site. Specific textual content that provided insights into the types of barriers at each site was used in the design of the CME lectures. As an example, if a participant identified that radiologists were not routinely notified that a head CT involved a tPA-eligible patient, the CME lecture at that site could contain specific advice on optimizing communication between clinicians and radiologists.

Table 2. Coding Guide and Barrier Definitions

Additional file 2. This is the coding guide developed by the investigators with conventions used in assigning themes.

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Responses from participants were coded into nine major themes. The three external barriers were environmental factors (e.g., availability of intensive care units, ED crowding, pharmacy or radiology), patient factors (e.g., failure to recognize symptoms, preference to arrive via car instead of ambulance), and guideline factors (issues with the structure or content of guidelines in general). The six internal barriers were the lack of familiarity, agreement, awareness, motivation, outcome expectancy, or self-efficacy. Each paragraph (the coding unit) was coded for all themes found; thus each paragraph could be assigned zero to nine themes. See Table 2 for a detailed description of all of the major coding themes.

Major themes were derived in advance of data collection. After completion of phase 1, the two coders independently used the phase 1 data to inductively derive minor themes, including the various aspects of acute stroke presentation and treatment, conceptual models of acute stroke presentation, and the overall process of stroke onset to outcome. These minor themes were then coded for both phase 1 and 2 data for the development of the site-specific educational interventions. Barriers were also related to the various phases of acute stroke presentation and treatment. External barriers were related to the conceptual models of the acute stroke presentation. Barriers were related to the points in the overall process from stroke onset to outcome.


Phase 1 of the barrier assessments occurred at the initial site investigators' meeting on 3/26/2007. Phase 2 of the barrier assessments was conducted at each of the intervention hospitals from 6/12/2007 to 10/05/2007. The thematic analysis occurred from July to October 2007 and was used to design and prioritize educational interventions for the trial. The short lead time from barrier assessment to intervention was the rationale for the semi-quantitative approach (relative barrier proportions) that was utilized to determine the most discussed barriers from each site.


Since the external barriers of environmental and patient factors comprised most of the cited barriers, sub-categories were inductively derived from these two major themes to better inform the sites during the educational intervention. The derived subcategory themes of barriers external to the EP are described in Table 3 and provided within the framework of acute stroke presentation in Figure 2. The temporal process of stroke occurrence, presentation, treatment and recovery that leads to the final outcome is shown.

Table 3. Sub Categories of Identified Barriers External to the Individual Provider

thumbnailFigure 2. Relationship of acute stroke care process to barriers external to the emergency physician. The pathway shows the process a patient would go through when presenting with an acute stroke. The relationship of the identified external barriers to each point on this pathway is demonstrated here.

Examples of responses which are illustrative of important internal barriers are provided in Table 4. The quotations were edited for readability but no substantive changes were made. Text added for clarity has been placed in brackets. When considering the internal barriers, nine of twelve hospitals cited guideline familiarity as most important (see Figure 3). Additionally, for eight of twelve hospitals, the top three cited barriers were guideline familiarity, provider motivation, and provider outcome expectancy. In contrast, lack of agreement with guidelines and lack of awareness of the presence of guidelines were the least important barriers for ten of the twelve hospitals.

Table 4. Barriers Internal to the Individual Provider

thumbnailFigure 3. Distribution of cited barriers by individual hospital. Overall, the dominant barriers reported were external barriers and patient related factors.

The external barriers of environmental factors and patient factors dominated the barriers discussed for every hospital (Figure 3a) and for all participant types. A great deal of discussion focused on the environmental (or systems based) barrier of radiology, particularly regarding failure of adequate communication of the time sensitive nature of computed tomography (CT) ordering and interpretation. Interestingly, radiologists in some cases also discussed the lack of a specific process to alert them to the emergent nature of these CT scans. The limited availability of neurology was frequently discussed as well. In some areas this was a general lack of neurologists and in others it reflected a lack of evening/weekend coverage. Fear of liability both for giving and not giving tPA also received moderate attention as an external barrier.

Within the internal barriers (Figure 3b), most participants identified lack of guideline familiarity as a large component of their hospital's barriers. Most also had either outcome expectancy or motivation as an important barrier. The lack of self-efficacy appeared to be an important contributing barrier in several hospitals as well. When considering barriers organized by type of provider, the external barriers of environment and patient-controlled factors again dominated the perceived barriers (see Figure 4a). Regarding the internal barriers, nurses perceived lack of guideline familiarity as the most important barrier whereas physicians (both EPs and neurologists) perceived physician motivation as the primary barrier (see Figure 4b). Of the barriers defined as internal to physicians, the most important were familiarity with and motivation to adhere to the guidelines, self-efficacy, and outcome expectancy.

thumbnailFigure 4. Distribution of cited barriers by acute stroke care provider type. In general, nurses perceived lack of guideline familiarity as the biggest barrier whereas physicians (both EM and neurologists) perceived physician motivation as the primary barrier.


We investigated barriers to the provision of thrombolysis for stroke in a randomly selected group of community hospitals, focusing on the beliefs and experiences of health care providers most likely to be involved in providing acute stroke care. In general, almost half of the discussed barriers were considered external to the provider (e.g., systems issues, patient delays). The barriers internal to the provider were prioritized according to a model of physician behavior change[9].

The hospital barrier assessment process was important because although the top barriers were similar across sites, there was still inter-site variability. This stresses the need for interventions targeted to individual hospital and provider barriers. The optimal and efficient design of interventions to improve health processes requires a firm understanding of the knowledge and attitudes of the group targeted for the intervention[17]. This is analogous to establishing understanding of the pathophysiology and course of disease prior to the development of a treatment.

Past work on barriers to thrombolysis has focused on patient- or hospital-level characteristics and not provider-level barriers[4,6]. Our focus centered on the knowledge and attitudes of the providers at the bedside who were deciding whether and how to offer thrombolysis to stroke patients. Providers were cognizant of the importance of delayed presentation and the difficulties inherent in patient and family symptom recognition and often reported these as important barriers. Further work on the exploration of the interaction between the physician offering therapy and the patient or family member deciding on receiving therapy could provide additional insights into improving treatment rates.

The finding that EPs frequently cited lack of motivation to adhere to, and lack of familiarity with, the content of guidelines for stroke thrombolysis is intuitive. An example of this is the observation that physicians will repeatedly examine patients looking for improvement to justify withholding treatment. Prior and current ongoing methods of examining thrombolytic utilization and eligibility have not captured this. Designing interventions that recognize treatment should occur promptly to combat this hesitancy is important, particularly since providers may delay even further with the recent publication of data that potentially expands the time window for thrombolysis[18,19]. The lack of familiarity with the guidelines cited as a barrier by many respondents often focused on specific procedural issues such as blood pressure control. Difficulty with these and other aspects of the post-treatment guidelines have been observed in prior cohorts of thrombolytic treated stroke patients, although prior investigations focusing on clinician failure to treat patients meeting criteria have been limited[20]. The qualitative methodology utilized in the current investigation was crucial to identifying these important issues and others that have not been captured by prior reviews of thrombolytic cases or EP surveys.

The relative minimal importance ascribed to a lack of agreement with the guidelines is surprising, especially in light of the past controversy that stroke thrombolysis has generated within the field of emergency medicine[21,22]. This implies that changing physician practice with regard to stroke thrombolysis may not require changing minds, per se. Instead, increasing physician familiarity, confidence (self-efficacy), and motivation to deliver the treatment are likely to be of higher yield. Further investigation of the limited guideline disagreement perceived by EPs will be needed. Further conclusions on this topic may be facilitated through quantitative survey data. In addition, a small number of hospitals seemed to have clusters of higher perceived guideline disagreement. This suggests that clustering within physician groups is an important consideration for evaluating and improving barriers to care.

Our separate interviews with nurses and EPs provided unique findings. The repeated re-examination phenomenon was described by emergency department nurses. This specific example typifies the perceived barrier that was cited as most important by many nurses: lack of motivation. The picture that is painted is that of the clinician who is uncomfortable and unsure when faced with the potential of having to administer a thrombolytic agent. It is doubtful if this barrier would have been articulated as clearly without interviews restricted to individual provider types.

This work has several important limitations. We did not generally seek "saturation" by performing repeat focus groups with the intent of further delving more deeply into specific themes. We used an existing taxonomy to classify responses, which might have missed barriers that did not fit well into any of the categories. The integration of these results with quantitative methods and overall response to the targeted educational interventions (as evidenced by change in tPA treatment rates), is not possible at this point in the overall trial. We focused only on 12 hospitals within Michigan, and while these hospitals came from diverse geographic and socioeconomic areas, these findings may not be widely generalizable. There is a potential that participants in the focus groups and interviews were generally more positive towards stroke thrombolysis, although it is also plausible that participants with strong negative opinions would also be extremely motivated to participate. Overall it appears that a range of opinions were represented by our participants. This contributes to the richness of the findings of the current investigation.


In summary, healthcare providers responsible for acute stroke treatment perceive environmental and patient factors as the most important barriers to adherence with the AHA acute stroke guidelines. With respect to internal barriers, nurses perceived lack of guideline familiarity as the biggest barrier whereas physicians (both EPs and neurologists) perceived physician motivation as the primary barrier. Overall, the minimal discussion of lack of physician agreement as a barrier is interesting in light of ongoing controversy over the use of tPA for stroke in the field of emergency medicine. Greater knowledge of the barriers which impede the widespread adoption of acute stroke thrombolysis is crucial to designing effective educational interventions to improve guideline adherence and may be informative in other areas where difficult risk/reward decisions are made on an emergent basis.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

PAS conceived, obtained funding, and supervised this study. WJM developed the analysis and data collection methods. WJM, SAF AMS, and PAS all participated in data collection. WJM and JJM performed the data analysis. WJM wrote the first draft of the paper; all authors have read and edited the paper for content and approve of this manuscript. WJM and JJM have full access to all of the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis.


This study was funded by the National Institutes of Neurologic Disorders and Stroke. (R01-NS 050372). The sponsor did not have any direct role in: the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript. Lingling Zhang provided methodological support, along with advice and training in the use of NVIVO 7. Andrew Barnosky, Barbara Smith, and Deneil Kolk each facilitated focus groups at the Champions Meeting. Jeff Clevenger transcribed the majority of the audio recordings.This work was presented in abstract form at the International Stroke Conference, February 2008, New Orleans, LA. This article was made available as Open Access with the support of the University of Michigan COPE Fund,


  1. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y, Committee ftAHAS, Stroke Statistics Subcommittee: Heart Disease and Stroke Statistics--2008 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.

    Circulation 2008, 117(4):e25-146. PubMed Abstract | Publisher Full Text OpenURL

  2. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EFM: Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.

    Stroke 2007, 38(5):1655-1711. PubMed Abstract | Publisher Full Text OpenURL

  3. del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr, on behalf of the American Heart Association Stroke Council: Expansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator. A Science Advisory From the American Heart Association/American Stroke Association.

    Stroke 2009.



  4. Barber PA, Zhang J, Demchuk AM, Hill MD, Buchan AM: Why are stroke patients excluded from TPA therapy?: An analysis of patient eligibility.

    Neurology 2001, 56(8):1015-1020. PubMed Abstract | Publisher Full Text OpenURL

  5. Schumacher HC, Bateman BT, Boden-Albala B, Berman MF, Mohr JP, Sacco RL, Pile-Spellman J: Use of Thrombolysis in Acute Ischemic Stroke: Analysis of the Nationwide Inpatient Sample 1999 to 2004.

    Annals of Emergency Medicine 2007, 50(2):99-107. PubMed Abstract | Publisher Full Text OpenURL

  6. Kwan J, Hand P, Sandercock P: A systematic review of barriers to delivery of thrombolysis for acute stroke.

    Age Ageing 2004, 33(2):116-121. PubMed Abstract | Publisher Full Text OpenURL

  7. Morgenstern LB, Bartholomew LK, Grotta JC, Staub L, King M, Chan W: Sustained Benefit of a Community and Professional Intervention to Increase Acute Stroke Therapy.

    Arch Intern Med 2003, 163(18):2198-2202. PubMed Abstract | Publisher Full Text OpenURL

  8. Greco PJ, Eisenberg JM: Changing physicians' practices.

    N Engl J Med 1993, 329(17):1271-1273. PubMed Abstract | Publisher Full Text OpenURL

  9. Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, Rubin HR: Why don't physicians follow clinical practice guidelines? A framework for improvement.

    Jama 1999, 282(15):1458-1465. PubMed Abstract | Publisher Full Text OpenURL

  10. Curry LA, Nembhard IM, Bradley EH: Qualitative and Mixed Methods Provide Unique Contributions to Outcomes Research.

    Circulation 2009, 119(10):1442-1452. PubMed Abstract | Publisher Full Text OpenURL

  11. Scott PA: Enhancing Community Delivery of Tissue Plasminogen Activator in Stroke Through Community-Academic Collaborative Clinical Knowledge Translation.

    Emergency Medicine Clinics of North America 2009, 27(1):115-136. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  12. Fonarow GC, Reeves MJ, Smith EE, Saver JL, Zhao X, Olson DW, Hernandez AF, Peterson ED, Schwamm LH, Committee obotG-SS, Investigators: Characteristics, Performance Measures, and In-Hospital Outcomes of the First One Million Stroke and Transient Ischemic Attack Admissions in Get With The Guidelines-Stroke.

    Circ Cardiovasc Qual Outcomes 2010, 3(3):291-302. PubMed Abstract | Publisher Full Text OpenURL

  13. Leira EC, Pary JK, Davis PH, Grimsman KJ, Adams HP Jr: Slow Progressive Acceptance of Intravenous Thrombolysis for Patients With Stroke by Rural Primary Care Physicians.

    Arch Neurol 2007, 64(4):518-521. PubMed Abstract | Publisher Full Text OpenURL

  14. White-Bateman SR, Schumacher HC, Sacco RL, Appelbaum PS: Consent for Intravenous Thrombolysis in Acute Stroke: Review and Future Directions.

    Arch Neurol 2007, 64(6):785-792. PubMed Abstract | Publisher Full Text OpenURL

  15. Meurer WJ, Frederiksen SM, Majersik JJ, Zhang L, Sandretto A, Scott PA: Qualitative data collection and analysis methods: the INSTINCT trial.

    Acad Emerg Med 2007, 14(11):1064-1071. PubMed Abstract | Publisher Full Text OpenURL

  16. Tong A, Sainsbury P, Craig J: Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups.

    Int J Qual Health Care 2007, 19(6):349-357. PubMed Abstract | Publisher Full Text OpenURL

  17. Campbell M, Fitzpatrick R, Haines A, Kinmonth AL, Sandercock P, Spiegelhalter D, Tyrer P: Framework for design and evaluation of complex interventions to improve health.

    Bmj 2000, 321(7262):694-696. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  18. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D, the ECASS Investigators: Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke.

    N Engl J Med 2008, 359(13):1317-1329. PubMed Abstract | Publisher Full Text OpenURL

  19. Lyden P: Thrombolytic Therapy for Acute Stroke -- Not a Moment to Lose.

    N Engl J Med 2008, 359(13):1393-1395. PubMed Abstract | Publisher Full Text OpenURL

  20. Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA: Use of Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: The Cleveland Area Experience.

    Jama 2000, 283(9):1151-1158. PubMed Abstract | Publisher Full Text OpenURL

  21. Hoffman J, Schriger D: A graphic reanalysis of the NINDS trial.

    Annals of Emergency Medicine 2009, 54(3):329-336. PubMed Abstract | Publisher Full Text OpenURL

  22. Mitka M: Tensions Remain Over tPA for Stroke.

    JAMA 2003, 289(11):1363-1364. PubMed Abstract | Publisher Full Text OpenURL

Pre-publication history

The pre-publication history for this paper can be accessed here: