Q J Med 2004; 97: 273-279
QJM vol. 97 no. 5 (c) Association of Physicians 2004; all rights reserved.
Improving the efficiency of delivery of thrombolysis for acute stroke: a systematic review
From the 1University Department of Geriatric Medicine, Southampton General Hospital, , Southampton, UK, 2Department of Neurology, Royal Melbourne Hospital, Parkville, Australia, and 3Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
Received 20 November 2003 and in revised form 13 January 2004
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Background: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is licensed for use within 3 h of acute ischaemic stroke. The less the delay to treatment, the more likely it is to be effective.
Aims: To assess the effectiveness of interventions designed to overcome barriers to rapid administration of thrombolytic therapy.
Design: Systematic review of previous clinical studies.
Methods: We searched for studies that evaluated the effect of an intervention to reduce delays to administration of rt-PA. We searched MEDLINE, EMBASE, the trials register of the Cochrane Stroke Group, and the Cochrane Controlled Trials Register. We sought randomized and non-randomized controlled trials, before-and-after studies, interrupted time series, and observational studies.
Results: We identified 10 non-randomized studies that evaluated interventions that could speed up admission to hospital and administration of rt-PA. The types of interventions included: (a) education programmes for the public to improve their knowledge about symptoms of acute stroke; (b) training programmes for paramedical staff to improve their accuracy of stroke diagnosis and hasten transport of the patient to hospital; (c) helicopter transfer of patients to hospital; (d) training programmes in acute stroke therapy for emergency department staff; and (e) re-organization of in-hospital systems to streamline acute stroke care. Several programmes were multifaceted interventions.
Discussion: We identified important areas that could be targets for interventions to improve the efficiency of delivering thrombolysis for acute stroke. Multifaceted programmes might be more likely to be successful in reducing delays to therapy.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) has recently received a European license for treatment of acute ischaemic stroke. The benefit of thrombolysis is the greatest when given very early after stroke; rt-PA administered within 3 h of ischaemic stroke onset can reduce the absolute risk of being dead or dependent at 3 months by up to 16%.1 Only a small proportion of patients are currently treated, although many more might be treated if they were brought to hospital and assessed more rapidly.2–8
Several types of barriers to early delivery of thrombolytic therapy have been described. Examples include: (a) delay in recognising the symptoms of stroke or seeking help;9–11 (b) the general practitioner is contacted first, rather than the emergency services;6,11,12 (c) stroke is triaged as non-urgent in the emergency department;13–15 (d) delays in neuroimaging;16,17 and (e) inefficient in-hospital acute stroke care.9,11,12 The presence of these barriers means that many stroke patients are denied thrombolytic therapy,18 and different interventions have been implemented to overcome them. This systematic review aimed to assess the effects of such interventions.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
We sought to identify: (a) randomized controlled trials that compared an intervention with control, or one intervention versus another; (b) quasi-randomized trials; (c) non-randomized clinical studies; (d) before-and-after studies; (e) interrupted time series; and (f) uncontrolled observational studies. Studies were considered if they had assessed the delay to hospital admission and/or thrombolytic therapy, or the proportion of patients receiving thrombolytic therapy (usually within three hours).
We searched the trials register of the Cochrane Stroke Group, the Cochrane Controlled Trials Register (Central/CCTR) of the Cochrane Library (year 2002, issue 4), and MEDLINE and EMBASE, in December 2002. Titles, keywords and abstracts of all downloaded citations were screened, and paper copies of those meeting our selection criteria were retrieved. Two reviewers (JK, PAGS) independently assessed the methodological quality of all included studies and recorded their findings. Two reviewers (JK, PH) then extracted the data onto a pre-defined data extraction form. Full details of the search strategies are available from the authors.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
We scanned a total of 22 052 titles and abstracts, and retrieved 119 publications in full text. From these, we identified 10 studies that either described or evaluated the effects of interventions designed to improve the efficiency of delivering thrombolytic therapy for acute stroke.
Quality of the studies
We did not identify any randomized controlled trials. There were 10 non-randomized studies with a total of at least 6345 patients19–28 (one study published in abstract form did not state the number of recruited patients22). Of these, four were before-and-after studies,19,22,24,28 one was a non-randomized clinical study,20 and five were observational studies.21,23,25–27 Eight were carried out in the US, two in Canada and one in Germany. Only two studies stated that the patients were consecutively recruited.20,27 The description of study methodology and the intervention was generally satisfactory.
Identified interventions
From these 10 studies, we identified different types of interventions that were hoped to improve the efficiency of delivery of thrombolytic therapy for acute stroke (Table 1). These interventions targeted both the pre-hospital and in-hospital phases of acute stroke care (Tables 2 and 3).
|
|
|
Combined educational programmes for the public, paramedical staff, and emergency department (ED) staff
Four studies evaluated these three types of interventions. The aim of educating the public was to improve the knowledge of symptoms of stroke, and emphasize the need to seek urgent help. The aim of training the paramedical and ED staff was to speed up pre- and in-hospital stroke care, including the use of thrombolysis in selected patients.19,21,24,28
In study 1, Alberts et al. developed an educational programme for the public primary-care physicians and ED staff. This was supplemented by the use of helicopters for rapid transfer of patients to the specialist centre. This before-and-after study showed that, after the educational programme, the proportion of patients with ischaemic stroke arriving within 24 h of onset increased from 37% to 86%.19
In study 2, Barsan et al. developed an educational programme for the public, paramedical staff and ED staff. Over the course of this observational study (2.5 years), the mean delay from stroke onset to hospital arrival was reduced from 3.2 to 1.5 h. Simultaneously, the use of emergency services amongst admitted stroke patients increased from 39% in the first quartile of the study to 60% in the fourth quartile. Overall, 3.5% of patients received rt-PA.21
In study 3, Morgenstern et al. developed an educational programme for the public and ED staff; the public was also encouraged to be ‘assertive in asking the physician about rt-PA’. This was a before-and-after study with a parallel comparison group. In the intervention group, the proportion of patients receiving rt-PA significantly increased from 1.4% to 5.8%; no significant difference was found in the parallel group.28
In study 4, Behrens et al. developed a training programme for paramedical and ED staff. The staff were trained in: (a) clinical assessment of patients with suspected stroke and the need to transfer them immediately to hospital; (b) rapid triage of stroke patients in the ED, resulting in urgent computed tomography (CT) scanning and administration of rt-PA or other forms of therapy. In this before-and-after study, the training programme reduced the mean delay from symptom onset to hospital arrival (5.2 to 3.3 h) and from diagnosis to start of therapy (2.6 to 1.6 h). The proportion of patients arriving within 3 h significantly increased from 2% to 15%, and the proportion receiving rt-PA increased from 2% to 11%.24
Specific training programmes for the paramedical staff to improve accuracy of diagnosis and speed up transfer of patient to hospital
Two studies evaluated this type of intervention.23,27 In study 1, Harbison et al. designed a training programme for the paramedical staff to improve the accuracy of stroke diagnosis and speed up transfer of patients to hospital (the Rapid Ambulance Protocol). In this observational study, trained paramedical staff correctly diagnosed stroke or TIA in 83% of the patients, and the median delay from symptom onset to hospital arrival was 1.2 h. Delay to hospital arrival was greater if the general practitioner was initially contacted.23 In study 2, Silliman et al. designed a training programme for the paramedical staff about the use of rt-PA in patients with acute stroke. This was supplemented by the helicopter transfer of potentially eligible patients to the specialist centre. In this observational study, of the 111 patients with suspected stroke transferred by helicopter, 71% arrived at the hospital within 3 h, and 21% received rt-PA.27 The average cost of each helicopter transfer was $4623; helicopter charges were $3300 for lift-off plus $45 for every mile travelled. Although cost-effectiveness analysis was not conducted in this study, the authors remarked, ‘the increased costs (of using helicopter transfers) are small relative to the significant potential savings in rehabilitation and nursing home costs associated with this treatment modality’.27
Helicopter transfer of patients to hospital
This method of transferring patients to hospital was evaluated in Alberts et al and Silliman et al., the results of which are described above.19,27
Re-organization of in-hospital systems to streamline acute stroke care
Two studies evaluated this type of intervention.20,22 In study 1, Gomez et al. implemented a ‘Code Stroke’ protocol, which used a centralized pager system to alert all the members of the acute stroke team when a patient with suspected stroke arrived in the ED. This comparative study found that, compared with standard management, the ‘Code Stroke’ protocol significantly reduced the delay from hospital arrival to first medical assessment from 101 to 46 min, but there was no significant difference in delays from symptom onset to hospital arrival, or from first medical assessment to start of therapy.20 In study 2, Englander et al. implemented a continuous quality improvement scheme which involved new algorithms and evaluation forms for assessing patients presenting with acute stroke. In this before-and-after study, after the introduction of the scheme, all in-hospital delays were significantly reduced, including delay from hospital arrival to first medical assessment (45 to 10 min), from hospital arrival to CT scanning (117 to 46 min), and from hospital arrival to neurologist assessment (76 to 46 min).22
Multifaceted programmes
Two studies evaluated multifaceted programmes that involved several types of interventions applied simultaneously.25,26 In study 1, Riopelle et al. evaluated the Regional Acute Stroke Protocol (RASP) which contained three main elements: (a) training of paramedical staff; (b) training of ED staff including transfer of patients to nearby tertiary centre for thrombolysis; and (c) development of the acute stroke activation system at the regional stroke centre, which involved alerting the acute stroke team, immediate CT scanning, and administration of rt-PA. This observational study found that, of the 191 patients managed with the RASP, 42 (22%) received rt-PA. Using an estimated figure of 792 strokes occurring in the entire region, 5.3% would have received rt-PA.25,26 In study 2, Hill et al. evaluated a multifaceted programme that included: (a) education of the public; (b) training of the paramedical staff and ED staff; (c) development of the acute stroke team; (d) training of staff working in the neuro-observation unit on how to administer rt-PA; and (e) development of a daily TIA clinic. In this observational study, of the 1127 patients admitted with stroke, 2.6% received rt-PA. Throughout the study period, there were significant reductions in mean delay from symptom onset to hospital arrival (63 to 49 min), from symptom onset to CT scanning (113 to 90 min), and from symptom onset to start of rt-PA (168 to 147 min).25
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Interventions to improve the efficiency of acute medical services are difficult to assess by means of conventional parallel group RCTs. We were therefore not surprised by the failure to identify any RCTs in this review. Non-randomized studies are subject to bias, hence any conclusions about observed changes may be less reliable. We therefore sought to at least describe the types of interventions and provide a qualitative description of their putative effects. The heterogeneity of study designs precluded a formal meta-analysis.
Public educational campaigns
The public needs to know the symptoms of a stroke, and that urgent medical care should be sought if they are to have a chance to receive rt-PA within 3 h of onset.11 Two studies have demonstrated that public education campaigns through mass media could increase the public's knowledge of stroke symptoms and their risk factors, but did not assess the effects on delay to hospital arrival or use of rt-PA.29,30 In this review, we found four studies that involved not only education of the public, but also training of the paramedical staff, primary care physicians, and ED staff. This type of combined educational programme appeared to have some effect in reducing the delay to receiving thrombolysis, increasing the use of emergency ambulances, and increasing the proportion of patients receiving rt-PA. However, it remains unclear how intensive such campaigns should be and how frequently they should be repeated.
Paramedical staff training
A significant proportion of stroke patients are admitted within 3 h of stroke onset. An audit of 739 patients from 22 hospitals in the UK found that 37% of patients arrived within 3 h; this figure is similar to that found in other parts of Europe, the US, and China.14,31,32 To maximize the proportion of patients receiving rt-PA within 3 h, paramedical staff must be accurate in their diagnosis of stroke, so that those who might be eligible for thrombolysis can be transferred immediately to the appropriate stroke centre, whereas those with non-strokes (e.g. seizures, hypoglycaemia) are managed in the usual way. Various stroke assessment tools and training programmes have been shown to have a positive impact on the accuracy of pre-hospital diagnosis of stroke.3,33–35 Moreover, the studies included in this review found that training of paramedical staff could improve the speed of hospital admission. In the future, pre-hospital stroke care might even involve administration of a neuroprotective agent by paramedical staff.3
Implications for practice
We have identified several types of interventions that might speed up the delivery of thrombolysis for acute stroke. Although rt-PA should be administered speedily, the emergency physicians or stroke team must also follow strict guidelines if it is to be administered safely and adverse events are to be minimized.36,37 Moreover, as patients with possible stroke arrive at the hospital earlier, the emergency physicians should be aware of the increased chance of the diagnosis being a TIA, intracerebral haemorrhage, or non-stroke condition.38 Although many patients arriving early may not qualify to receive thrombolysis, at least they will be promptly admitted to an acute stroke unit for early physiological monitoring and multidisciplinary care.
The observed effects of each intervention are specific to the local organizational setting, so that it may not be applicable to every hospital or community. For instance, immediate assessment by the stroke team may not influence the use of thrombolysis if there is substantial delay to CT scanning.39 We found that multifaceted programmes might have greater effects than single interventions, but such programmes may also require substantial resources and effort to execute and their cost-effectiveness is unproven.
This review did not find enough evidence to advocate one single intervention that is most likely to increase access to, and usage of, thrombolytic therapy for acute stroke. However, it has identified several approaches which might be tailored to suit local circumstances and available resources.
Implications for research
Further research is needed to identify cost-effective strategies to make the process of diagnosing and treating patients with suspected acute stroke faster and more efficient.
|
Acknowledgments |
|---|
The authors are grateful to the Cochrane Stroke Group Editorial Base in Edinburgh, UK, for their assistance in designing and conducting the literature searches. The review was supported in part by a grant from the NHS Health Technology Assessment (HTA) Programme (Grant 98/02/02). The opinions and views expressed do not necessarily reflect those of the NHS Executive. The source of funding had no role in review design, data collection, data analysis, writing of the report, or decision to submit the paper for publication.
|
Footnotes |
|---|
Address correspondence to Dr J. Kwan, University Department of Geriatric Medicine, Level E Mailpoint 807, Southampton General Hospital, Tremona Road, Southampton SO16 6YD. e-mail: jk{at}1to1.org
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. Wardlaw JM, del Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2003; (3):CD000213.
2. Broadley SA, Thompson PD. Time to hospital admission for acute stroke: an observational study. Med J Aust 2003; 178:329–31.[Web of Science][Medline]
3. Suyama J, Crocco T. Prehospital care of the stroke patient. Emerg Med Clin North Am 2002; 20:537–52.[CrossRef][Web of Science][Medline]
4. Engelstein E, Margulies J, Jeret JS. Lack of t-PA use for acute ischaemic stroke in a community hospital: high incidence of exclusion criteria. Am J Emerg Med 2000; 18:257–60.[CrossRef][Web of Science][Medline]
5. Harraf F, Sharma AK, Brown MM, Lees KR, Vass RI, Kalra L. A multicentre observational study of presentation and early assessment of acute stroke. Br Med J 2002; 325:17–20.
6. Lacy CR, Suh DC, Bueno M, Kostis JB. Delay in presentation and evaluation for acute stroke : Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E.). Stroke 2001; 32:63–9.
7. O’Connor RE, McGraw P, Edelsohn L. Thrombolytic therapy for acute ischemic stroke: why the majority of patients remain ineligible for treatment. Ann Emerg Med 1999; 33:9–14.[CrossRef][Web of Science][Medline]
8. Kwan J, Hand P, Leigh-Brown A, Sandercock P. In Europe, how many stroke patients can be treated with and benefit from intravenous rt-PA within 6 hours? [Abstract] Stroke 2000; 31:2837.
9. Feldmann E, Gorgon N, Brooks JM, Brass LM, Fayad PB, Sawaya KL, Nazareno F, Levine SR. Factors associated with early presentation of acute stroke. Stroke 1993; 24:1805–10.
10. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Factors delaying hospital admission in acute stroke. The Copenhagen Stroke Study. Neurology 1996; 47:383–7.
11. Wester P, Radberg J, Lundgren B, Peltonen M. Factors associated with delayed admission to hospital and in-hospital delays in acute stroke and TIA: a prospective, multicenter study. Stroke 1999; 30:40–8.
12. Morris DL, Rosamond W, Madden K, Schultz C, Hamilton S. Prehospital and emergency department delays after acute stroke: The Genentech Stroke Presentation Survey. Stroke 2000; 31:2585–90.
13. Ferro JM, Melo TP, Oliveira V, Crespo M, Canhao P, Pinto AN. An analysis of the admission delay of acute strokes. Cerebrovasc Dis 1994; 4:72–5.
14. Kothari R, Jauch E, Broderick J, Brott T, Sauerbeck L, Khoury J, Liu T. Acute stroke: delays to presentation and emergency department evaluation. Ann Emerg Med 1999; 33:3–8.[Web of Science][Medline]
15. Ravindrane A, Croft-Baker J, Jarrett D, Severs MP. Causes of delay in hospital assessment after stroke. Age Ageing 2000; 29:57.
16. Lin CS, Tsai J, Woo P, Chang H. Prehospital delay and emergency department management of ischemic stroke patients in Taiwan, R.O.C. Prehosp Emerg Care 1999; 3:194–200.[Medline]
17. Tilley BC, Lyden PD, Brott TG, Lu M, Levine SR, Welch KMA. Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischaemic stroke. Arch Neurol 1997; 54:1466–74.
18. Evenson KR, Rosamond W, Morris DL. Prehospital and in-hospital delays in acute stroke care. Neuroepidemiology 2001; 20:65–76.[CrossRef][Web of Science][Medline]
19. Alberts MJ, Perry A, Dawson DV, Bertels C. Effects of public and professional education on reducing the delay in presentation and referral of stroke patients. Stroke 1992; 23:352–6.
20. Gomez CR, Malkoff MD, Sauer CM, Tulyapronchote R, Burch CM, Banet GA. Code stroke. An attempt to shorten inhospital therapeutic delays. Stroke 1994; 25:1920–3.[Abstract]
21. Barsan WG, Brott TG, Broderick JP, Haley EC, Jr., Levy DE, Marler JR. Urgent therapy for acute stroke. Effects of a stroke trial on untreated patients. Stroke 1994; 25:2132–7.[Abstract]
22. Englander RN, Morich DH, Minniti MM. Accelerating the evaluation of acute stroke patients in a community hospital. Neurology 1998; 50:A114 (Abstract P02.091).
23. Harbison J, Massey A, Barnett L, Hodge D, Ford GA. Rapid ambulance protocol for acute stroke. Lancet 1999; 353:1935.[CrossRef][Web of Science][Medline]
24. Behrens S, Daffertshofer M, Interthal C, Ellinger K, Van Ackern K, Hennerici M. Improvement in stroke quality management by an educational programme. Cerebrovasc Dis 2002; 13:262–6.[CrossRef][Web of Science][Medline]
25. Hill MD, Barber PA, Demchuk AM, Sevick RJ, Newcommon NJ, Green T, Buchan AM. Building a ‘brain attack’ team to administer thrombolytic therapy for acute ischaemic stroke. Can Med Assoc J 2000; 162:1589–93.[Medline]
26. Riopelle RJ, Howse DC, Bolton C, Elson S, Groll DL, Holtom D, Brunet DG, Jackson AC, Melanson M, Weaver DF. Regional access to acute ischemic stroke intervention. Stroke 2001; 32:652–5.
27. Silliman SL, Quinn B, Huggett V, Merino JG. Use of a field-to-stroke center helicopter transport program to extend thrombolytic therapy to rural residents. Stroke 2003; 34:729–33.
28. Morgenstern LB, Staub L, Chan W, Wein TH, Bartholomew LK, King M, Felberg RA, Burgin WS, Groff J, Hickenbottom SL, Saldin K, Demchuk AM, Kalra A, Dhingra A, Grotta JC. Improving delivery of acute stroke therapy: The TLL Temple Foundation Stroke Project. Stroke 2002; 33:160–6.
29. Stern EB, Berman M, Thomas JJ, Klassen AC. Community education for stroke awareness: An efficacy study. Stroke 1999; 30:720–3.
30. Becker KJ, Fruin MS, Gooding TD, Tirschwell DL, Love PJ, Mankowskia TM. Community-based education improves stroke knowledge. Cerebrovasc Dis 2001; 11:34–43.[CrossRef][Web of Science][Medline]
31. Azzimondi G, Bassein L, Fiorani L, Nonino F, Montaguti U, Celin D, Re G, D’Alessandro R. Variables associated with hospital arrival time after stroke. Effect of delay on the clinical efficiency of early treatment. Stroke 1997; 28:537–42.
32. Wang XD, Guo H, Zhang XY, Zhu H, Li YH, Zhou G. An observation on the time of hospital arrival and correct diagnosis with CT in acute cerebral stroke patients. Cerebrovasc Dis 1997; 7:89–93.
33. Kidwell CS, Starkman S, Eckstein M, Weems K, Saver JL. Identifying stroke in the field. Prospective validation of the Los Angeles prehospital stroke screen (LAPSS). Stroke 2000; 31:71–6.
34. Kothari R, Barsan W, Brott T, Broderick J, Ashbrock S. Frequency and accuracy of prehospital diagnosis of acute stroke. Stroke 1995; 26:937–41.
35. Smith WS, Corry M, Fazackerley J, Isaacs M. Improved paramedic sensitivity in identifying stroke victims in the prehospital setting. Prehosp Emerg Care 1999; 3:207–10.[Medline]
36. Adams HP, Jr., Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Kwiatkowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the stroke council, American Heart Association. Stroke 1996; 27:1711–18.[Web of Science][Medline]
37. Buchan AM, Barber PA, Newcommon N, Karbalai HG, Demchuk AM, Hoyte KM, Klein GM, Feasby TE. Effectiveness of t-PA in acute ischemic stroke: outcome relates to appropriateness. Neurology 2000; 54:679–84.
38. Scott PA, Silbergleit R. Misdiagnosis of stroke in tissue plasminogen activator-treated patients: characteristics and outcomes. Ann Emerg Med 2003; 42:611–18.[CrossRef][Web of Science][Medline]
39. Beauchamp NJ, Jr., Barker PB, Wang PY, van Zijl PC. Imaging of acute cerebral ischemia. Radiology 1999; 212:307–24.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. R. White-Bateman, H. C. Schumacher, R. L. Sacco, and P. S. Appelbaum Consent for Intravenous Thrombolysis in Acute Stroke: Review and Future Directions Arch Neurol, June 1, 2007; 64(6): 785 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Yip and B. M. Demaerschalk Estimated Cost Savings of Increased Use of Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke in Canada Stroke, June 1, 2007; 38(6): 1952 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ehlers, G. Andersen, L. B. Clausen, M. Bech, and M. Kjolby Cost-Effectiveness of Intravenous Thrombolysis With Alteplase Within a 3-Hour Window After Acute Ischemic Stroke Stroke, January 1, 2007; 38(1): 85 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Agyeman, K. Nedeltchev, M. Arnold, U. Fischer, L. Remonda, J. Isenegger, G. Schroth, and H. P. Mattle Time to Admission in Acute Ischemic Stroke and Transient Ischemic Attack Stroke, April 1, 2006; 37(4): 963 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hanley and W. Hacke Critical Care and Emergency Medicine Neurology in Stroke Stroke, February 1, 2005; 36(2): 205 - 207. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||