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Stroke physician versus stroke neurologist: can anyone thrombolyse? A. Lee,1* A. Gaekwad,1* M. Bronca,1 L. Cheruvu,1 O. Davies,1 C. Whitehead,1 M. Agzarian2 and C. Chen3 1
Flinders Comprehensive Stroke Centre and Departments of 2Radiology and 3Neuro-ophthalmology, Flinders University of South Australia and Flinders
Medical Centre, Adelaide, South Australia, Australia
Key words thrombolysis, stroke, stroke physician, stroke neurologist. Correspondence Andrew Lee, Flinders Comprehensive Stroke Centre, Flinders University of South Australia and Medical Centre, Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia. Email: andrew.lee@flinders.edu.au Received 2 October 2014; accepted 17 December 2014. doi:10.1111/imj.12673
Abstract Background/Aim: The aim of this study is to compare the outcomes of thrombolysis under standard clinical settings between subjects treated by a stroke neurologist versus those treated by a non-neurologist stroke physician. Methods: Single-centre, observational cohort study of subjects thrombolysed in a calendar year, stratified according to the physician type authorising thrombolysis. Endpoints measured include proportion of subjects with symptomatic intracranial haemorrhage, door-to-needle time, change in National Institute of Health Stroke Scale and discharge destination. Results: Forty-nine subjects with a mean age 76 ± 16 years underwent thrombolysis, 21 were under the care of a stroke neurologist and 28 by a non-neurologist stroke physician. No symptomatic intracranial haemorrhages were observed. There was no difference in terms of door-to-needle time, proportion of individuals with haemorrhagic transformation, mortality or discharge destination between the two groups. Conclusion: Due to the single-centre, observational nature of this study, the equivalent outcomes between those thrombolysed by a stroke neurologist versus those thrombolysed by a stroke physician must be interpreted with caution pending further studies. Nevertheless, in the current setting, no signal for harm has been detected. This study is unique as it is the first to our knowledge comparing outcomes between a neurologist and non-neurologist following thrombolysis.
Introduction Stroke is the second largest killer worldwide behind ischaemic heart disease and is the number one cause of disability.1,2 Administration of anti-platelets within 48 h of ischaemic stroke, the admission to a comprehensive stroke unit and the use of intravenous tissue plasminogen activator (tPA) for ischaemic stroke within 4.5 h of treatment onset are the primary interventions demonstrating a reduction in morbidity and mortality.3 While in many countries, neurologists look after stroke, the multidisciplinary approach to stroke care has resulted in other physicians who also manage stroke patients on stroke units. In some regions, there are specific training programmes for such stroke specialists,
*Authors contributed equally. Funding: A. Lee was funded by an NHMRC-NICS Fellowship during this study. Conflict of interest: None.
termed stroke physicians.4 Due to the large number of incident strokes, increasing numbers of non-neurologist stroke physicians may be needed to staff stroke units. There is controversy as to the appropriateness of this approach. Advocates argue that much of the care of the stroke patient revolves around dealing with complications that are more general medical then neurological and that the coordination of a multidisciplinary team is more suited to those with training in geriatric or rehabilitation medicine.5 The contrary argument states that the brain is the province of the neurologist and the diagnosis paramount, and therefore the neurologist is the specialist most appropriate to treat stroke.6 The use of tPA is arguably the most complicated intervention done by a stroke specialist with the most severe adverse event being an intracranial haemorrhage. It has been demonstrated that where there are protocol violations, the risk of intracranial haemorrhage is significant. On the other hand, some groups have demonstrated that the risk of causing an intracranial haemorrhage when a stroke mimic is thrombolysed is minimal.7
© 2014 Royal Australasian College of Physicians
305
Lee et al.
While there is evidence that a stroke trained neurologist may have better outcomes then a general neurologist,8 there has never been a trial done to test the hypothesis of whether a non-neurologist stroke physician can thrombolyse with comparable results to a stroke neurologist. As stroke thrombolysis outcome is dependent not just on a correct diagnosis, but rather stringent adherence to protocols, coupled with good clinical correlation and neuroimaging, then we hypothesise that similar outcomes should occur, irrespective of whether treatment is delivered by a neurologist or a non-neurologist.
Methods Approval was given by the Southern Human Research Ethics Committee for analysis and publication of data as part of a quality improvement audit of standard clinical practice.
Setting The Flinders Comprehensive Stroke Centre (FCSC) is a tertiary referral centre for stroke, and services the southern half of the population of South Australia. There is a statewide protocol for patients with stroke presenting within 4.5 h of symptom onset to be transferred to the FCSC via ambulance where possible. A ‘code stroke’ is activated prior to patient arrival. A code stroke team, consisting of resident medical staff, meets the patient at the door and facilitates the movement of the patient through the system until tPA is delivered. Where possible, all subjects have a plain computed tomography (CT) brain followed by CT angiography of the extracranial neck vessels and circle of Willis and have CT perfusion done according to the standard protocols described by Wintermark et al.9 Thereafter, the clinical and radiological information is discussed with a stroke specialist, and authorisation for tPA delivery is given. The tPA is delivered within coronary care. There is a set protocol for thrombolysis delivery with strict adherence to guideline-based indications and contraindications for tPA delivery. This protocol is specific to the FCSC. The FCSC is staffed by four stroke specialists. There is one fellowship trained stroke neurologist (AL) and three geriatricians who have either completed a fellowship in stroke medicine (LC and OD) or have considerable experience in the practice of stroke medicine (CW). These three are termed stroke physicians. Prior to going on the roster for thrombolysis, each stroke physician underwent a mentored training programme consisting of education modules on the delivery of tPA and the interpretation of CT brain perfusion and
angiography. Following this, each had to undergo five tPA cases under the mentorship of a stroke neurologist before giving tPA on their own.
Data collection All patients undergoing thrombolysis are reviewed at a weekly neuro-radiology meeting where there is clinical correlation done between the stroke team and a fellowship trained neuro-radiologist (MA) who interprets the brain imaging. This correlation is crucial in defining the presence of either symptomatic intracranial haemorrhage or haemorrhagic transformation, as well as determining if a mimic had been thrombolysed. For consistency, the definition of a symptomatic intracranial haemorrhage is a haemorrhage post-tPA administration, resulting in a significant clinical decline as demonstrated by a four-point or more increase in the National Institute of Health Stroke Scale (NIHSS) and where in the opinion of the neuro-radiologist and the treating stroke team, the deterioration was due to the bleed as opposed to the size of the infarct. This definition is derived from the previously published ECASS-3 study.10 Data from each thrombolysis case, such as demographic details, door-to-needle time, the pre- and posttPA NIHSS, complications and discharge destination are maintained prospectively by a nurse practice consultant (MB). The post-tPA NIHSS is performed on the first day post-thrombolysis as part of the tPA protocol delivery. For the purpose of analysis, data were extracted from this database and combined with clinical and imaging data and imputed into a statistical software package by a research resident not involved in the clinical care of the patient (AG). Analysis was carried out by AL and verified by a separate clinician not involved in the care of stroke patients (CC) in order to minimise observer bias.
Statistical analysis This was carried out on Stata 9.2 (Statacorp, College Station, TX, USA). Continuous variables are described as a mean ± standard deviation (SD), while dichotomous are described as an absolute number with a percentage in parentheses. For the purpose of hypothesis testing, the data were separated into two cohorts, those patients undergoing thrombolysis under the care of the stroke neurologist versus those undergoing thrombolysis under a stroke physician. A student’s t-test was used for comparison of continuous variables, and Fisher’s exact test was used for comparison of dichotomous variables. An alpha of 0.05 was considered statistically significant. © 2014 Royal Australasian College of Physicians
306
Stroke thrombolysis
Table 1 Demographic details of subjects Demographics (n = 49) Age (years) Gender (male) Door to needle time (min) NIHSS pre-tPA NIHSS post-tPA
76 ± 16 54% 104 ± 40 10 ± 1 5±1
NIHSS, National Institute of Health Stroke Scale; tPA, tissue plasminogen activator.
present, but without symptomatic intracranial bleeding, defined by the presence of an increase of the NIHSS of four or more. In one subject, a spontaneous subdural haematoma was observed (Fig. 1; subject 6). In five of the six subjects, there was a reduction in the NIHSS between the pre- and post-tPA scores. There was one death recorded in this group (subject ID 1), the cause of death being aspiration pneumonia. Individual characteristics of these subjects are listed in Table 3. During this period, there were no stroke mimics thrombolysed.
Results
Discussion
Forty-nine subjects underwent thrombolysis in the calendar year 1 January 2013 to 31 December 2013 with 54% male and the mean age of subjects being 76 ± 16 years. The age of subjects ranged from 38 to 92 years. Forty-seven of the 49 patients underwent CT perfusion imaging. The mean door-to-needle time was 104 ± 40 min with a range of 47–213 min (Table 1). Even in the two subjects where perfusion was not done, their doorto-needle time of 65 min and 87 min, respectively, was not significantly shorter than those who had perfusion scanning. Using a paired t-test, there was a statistically significant reduction in the NIHSS by 5 ± 1 points from a mean NIHSS prior to tPA of 10 ± 1 to a mean of 5 ± 1 post-tPA (P < 0.000, t = 6.6, df = 40) for all subjects (Table 1). Twenty-one subjects (43%) were thrombolysed by a stroke neurologist, while the remaining were thrombolysed by stroke physicians. There was no statistical difference between the mean door-to-needle time, proportion of individuals with haemorrhagic transformation or the discharge destination between the two groups (Table 2). Forty-three subjects (87%) had no evidence of intracranial haemorrhage on CT brain scan 24 h post-tPA infusion. In five patients, haemorrhagic transformation was
Although stroke is the second largest killer behind heart disease and the number one cause of disability in many countries, the number of neurologists available to deal with the disease burden is limited. In some parts of the world, such as the United Kingdom, non-neurologists who have had specific training in stroke, termed stroke physicians, are involved in stroke care. Controversy exists regarding this model. Opponents point out that the neurologist is best suited to stroke care by virtue of their training and expected superior diagnostic skills.6 Proponents point out that the major advance in stroke care, the stroke unit, was designed by a nonneurologist and that a large amount of stroke care postdiagnosis involves secondary prevention.5 It has been pointed out that rather than stroke being the province of one or the other, combining the skills of both may result in a better outcome.11 There is evidence to suggest that when comparing the stroke neurologist to the general neurologist, the stroke neurologist has the better patient outcome.8 To date there has been no direct comparison between stroke physician and stroke neurologist in any facet of stroke care. As thrombolysis is based on a systems approach and modern brain imaging with perfusion-weighted imaging can aid in the selection of the stroke patient from
Table 2 Characteristics of subjects thrombolysed by either a stroke neurologist or stroke physician Stroke neurologist (number lysed = 21) Door-to-needle time (min) Symptomatic intracranial haemorrhage (%) Number of haemorrhagic transformation (%) Discharge destination Rehab at home Died Home Rehabilitation Nursing home
Stroke physician (number lysed = 28)
P-value
109 ± 1 0 2 (10%)
99 ± 8 0 4 (14%)
0.43 0.69
2 (10%) 2 (10%) 7 (33%) 8 (38%) 2 (10%)
0 (0) 2 (7%) 12 (43%) 13 (46%) 1 (4%)
0.48
© 2014 Royal Australasian College of Physicians
307
Lee et al.
Figure 1 Plain computer tomography brain scans post-tissue plasminogen activator administrations demonstrating haemorrhagic transformation in subjects 1–5, with subject 6 having a left hemisphere subdural haematoma.
the mimic, we hypothesised that there should be no difference in the outcomes between those lysed by a stroke neurologist versus a non-neurologist stroke physician. Our results tend to support this hypothesis as there was no difference in the proportion of individuals with haemorrhagic transformation, the discharge destination or door-to-needle time. Most importantly, there were no symptomatic intracranial haemorrhages post-tPA. On the contrary, there was a net benefit of tPA with a reduction of the mean NIHSS between pre- and post-tPA phases. While this result could be due to chance, we also believe that careful patient selection using advanced multi-modal imaging had a role to play. The final results of the START-EXTEND trial will be valuable in this regard.12 Nevertheless, these findings should be interpreted with caution due to some inherent internal study biases. First, this is an unblinded, observational study arising from a single-stroke centre. Even though the data extractor was not involved in the clinical care of the
patient, and there was a second person to perform the data analysis and the adjudication of patient outcomes occurred as a consensus during weekly neuroradiology meetings, it cannot be denied that all members of the research team come from the same institution. Thus, our result of equivalence could be a function of observer bias. Second, while this is a study of subjects thrombolysed in a calendar year, the sample size of 49 is relatively small, especially when dichotomising the group between those thrombolysed by a neurologist versus a stroke physician. For example, the acceptable proportion of intracranial haemorrhage would now be of the order of 1–2%. Therefore, to demonstrate a signal for harm would require a sample size in the order of 100–200 subjects. Our group intends to continue collecting data over the next 2–3 years, and a subsequent publication will demonstrate if our original hypothesis was true. Third, there is clearly an imbalance between the singlestroke neurologists versus three-stroke physicians.
Table 3 Characteristics of subjects who developed post-tPA bleeding ID
Age (years)
Gender
Physician
NIHSS pre-tPA
NIHSS post-tPA
Outcome
1 2 3 4 5 6
76 85 90 76 88 91
F F F M F M
Stroke physician Stroke physician Stroke neurologist Stroke physician Stroke neurologist Stroke physician
22 10 21 16 11 19
17 8 19 2 8 22
Dead Rehabilitation Nursing home Home Rehabilitation Rehabilitation
Subject numbers correspond with those on Figure 1. NIHSS, National Institute of Health Stroke Scale; tPA, tissue plasminogen activator. © 2014 Royal Australasian College of Physicians
308
Stroke thrombolysis
However, such an imbalance weighs the result in favour of finding the alternative hypothesis is true, or that there is a difference between stroke neurologists and stroke physicians. This was not the case. Nevertheless, our study provides valuable information on the question of equivalence of the stroke neurologist versus the stroke physician in thrombolysis. In the context of a stroke centre where there is a set protocol for thrombolysis delivery, coupled with a mentored-training programme for thrombolysis and the ready availability of perfusion imaging, there is no signal for harm if thrombolysis is delivered by a trained non-neurologist stroke physician. Our data should therefore be seen in the light of a hypothesis-generating study asking the question, is it the system or the physician that delivers the outcome in thrombolysis? One method of resolving this question would be to construct a cluster randomised trial of thrombolysis-naïve hospitals and having them staffed with either a group of stroke neurologists or a group of
References 1 Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095–128. 2 Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383: 245–55. 3 Hankey GJ, Warlow CP. Treatment and secondary prevention of stroke: evidence, costs, and effects on individuals and populations. Lancet 2007; 354: 1457–63.
stroke physicians, accompanied by a standard protocol for lysis. Such a study design could answer the question, but the logistics of randomising staff would be fraught with difficulties to say the least. An alternative would be to incorporate the speciality of origin of the physician delivering thrombolysis into existing thrombolysis registries and capturing data on the presence or absence of various components of a thrombolysis protocol. A key part of either the registry or the cluster randomised controlled trial would be the presence of an independent outcomes adjudication committee, which would remove the risk of observer bias.
Conclusion Our study demonstrates no difference in outcomes between thrombolysis delivered by a stroke neurologist versus a stroke physician, but it requires further hypothesis testing before a final conclusion can be made.
4 Royal College of Physicians. Stroke medicine 2012. 2012 [cited 2014 Jan 6]. Available from URL: http://www .rcplondon.ac.uk/specialty/stroke -medicine 5 Lees KR. Stroke is best managed by a neurologist: battle of the Titans. Stroke 2003; 34: 2764–5. 6 Caplan L. Stroke is best managed by neurologists. Stroke 2003; 34: 2763. 7 Chernyshev OY, Martin-Schild S, Albright KC, Barreto A, Misra V, Acosta I et al. Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia. Neurology 2010; 74: 1340–5. 8 Gillum LA, Johnston SC. Characteristics of academic medical centers and ischemic stroke outcomes. Stroke 2001; 32: 2137–42. 9 Wintermark M, Flanders AE, Velthuis B, Meuli R, van Leeuwen M, Goldsher D
et al. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke 2006; 37: 979–85. 10 Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359: 1317–29. 11 Donnan GA, Davis SM. Neurologist, internist, or strokologist? Stroke 2003; 34: 2765. 12 Ma H, Parsons MW, Christensen S, Campbell BCV, Churilov L, Connelly A et al. A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND). Int J Stroke 2012; 7: 74–80.
© 2014 Royal Australasian College of Physicians
309
Stroke physician versus stroke neurologist: can anyone thrombolyse? A. Lee,1* A. Gaekwad,1* M. Bronca,1 L. Cheruvu,1 O. Davies,1 C. Whitehead,1 M. Agzarian2 and C. Chen3 1
Flinders Comprehensive Stroke Centre and Departments of 2Radiology and 3Neuro-ophthalmology, Flinders University of South Australia and Flinders
Medical Centre, Adelaide, South Australia, Australia
Key words thrombolysis, stroke, stroke physician, stroke neurologist. Correspondence Andrew Lee, Flinders Comprehensive Stroke Centre, Flinders University of South Australia and Medical Centre, Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia. Email: andrew.lee@flinders.edu.au Received 2 October 2014; accepted 17 December 2014. doi:10.1111/imj.12673
Abstract Background/Aim: The aim of this study is to compare the outcomes of thrombolysis under standard clinical settings between subjects treated by a stroke neurologist versus those treated by a non-neurologist stroke physician. Methods: Single-centre, observational cohort study of subjects thrombolysed in a calendar year, stratified according to the physician type authorising thrombolysis. Endpoints measured include proportion of subjects with symptomatic intracranial haemorrhage, door-to-needle time, change in National Institute of Health Stroke Scale and discharge destination. Results: Forty-nine subjects with a mean age 76 ± 16 years underwent thrombolysis, 21 were under the care of a stroke neurologist and 28 by a non-neurologist stroke physician. No symptomatic intracranial haemorrhages were observed. There was no difference in terms of door-to-needle time, proportion of individuals with haemorrhagic transformation, mortality or discharge destination between the two groups. Conclusion: Due to the single-centre, observational nature of this study, the equivalent outcomes between those thrombolysed by a stroke neurologist versus those thrombolysed by a stroke physician must be interpreted with caution pending further studies. Nevertheless, in the current setting, no signal for harm has been detected. This study is unique as it is the first to our knowledge comparing outcomes between a neurologist and non-neurologist following thrombolysis.
Introduction Stroke is the second largest killer worldwide behind ischaemic heart disease and is the number one cause of disability.1,2 Administration of anti-platelets within 48 h of ischaemic stroke, the admission to a comprehensive stroke unit and the use of intravenous tissue plasminogen activator (tPA) for ischaemic stroke within 4.5 h of treatment onset are the primary interventions demonstrating a reduction in morbidity and mortality.3 While in many countries, neurologists look after stroke, the multidisciplinary approach to stroke care has resulted in other physicians who also manage stroke patients on stroke units. In some regions, there are specific training programmes for such stroke specialists,
*Authors contributed equally. Funding: A. Lee was funded by an NHMRC-NICS Fellowship during this study. Conflict of interest: None.
termed stroke physicians.4 Due to the large number of incident strokes, increasing numbers of non-neurologist stroke physicians may be needed to staff stroke units. There is controversy as to the appropriateness of this approach. Advocates argue that much of the care of the stroke patient revolves around dealing with complications that are more general medical then neurological and that the coordination of a multidisciplinary team is more suited to those with training in geriatric or rehabilitation medicine.5 The contrary argument states that the brain is the province of the neurologist and the diagnosis paramount, and therefore the neurologist is the specialist most appropriate to treat stroke.6 The use of tPA is arguably the most complicated intervention done by a stroke specialist with the most severe adverse event being an intracranial haemorrhage. It has been demonstrated that where there are protocol violations, the risk of intracranial haemorrhage is significant. On the other hand, some groups have demonstrated that the risk of causing an intracranial haemorrhage when a stroke mimic is thrombolysed is minimal.7
© 2014 Royal Australasian College of Physicians
305
Lee et al.
While there is evidence that a stroke trained neurologist may have better outcomes then a general neurologist,8 there has never been a trial done to test the hypothesis of whether a non-neurologist stroke physician can thrombolyse with comparable results to a stroke neurologist. As stroke thrombolysis outcome is dependent not just on a correct diagnosis, but rather stringent adherence to protocols, coupled with good clinical correlation and neuroimaging, then we hypothesise that similar outcomes should occur, irrespective of whether treatment is delivered by a neurologist or a non-neurologist.
Methods Approval was given by the Southern Human Research Ethics Committee for analysis and publication of data as part of a quality improvement audit of standard clinical practice.
Setting The Flinders Comprehensive Stroke Centre (FCSC) is a tertiary referral centre for stroke, and services the southern half of the population of South Australia. There is a statewide protocol for patients with stroke presenting within 4.5 h of symptom onset to be transferred to the FCSC via ambulance where possible. A ‘code stroke’ is activated prior to patient arrival. A code stroke team, consisting of resident medical staff, meets the patient at the door and facilitates the movement of the patient through the system until tPA is delivered. Where possible, all subjects have a plain computed tomography (CT) brain followed by CT angiography of the extracranial neck vessels and circle of Willis and have CT perfusion done according to the standard protocols described by Wintermark et al.9 Thereafter, the clinical and radiological information is discussed with a stroke specialist, and authorisation for tPA delivery is given. The tPA is delivered within coronary care. There is a set protocol for thrombolysis delivery with strict adherence to guideline-based indications and contraindications for tPA delivery. This protocol is specific to the FCSC. The FCSC is staffed by four stroke specialists. There is one fellowship trained stroke neurologist (AL) and three geriatricians who have either completed a fellowship in stroke medicine (LC and OD) or have considerable experience in the practice of stroke medicine (CW). These three are termed stroke physicians. Prior to going on the roster for thrombolysis, each stroke physician underwent a mentored training programme consisting of education modules on the delivery of tPA and the interpretation of CT brain perfusion and
angiography. Following this, each had to undergo five tPA cases under the mentorship of a stroke neurologist before giving tPA on their own.
Data collection All patients undergoing thrombolysis are reviewed at a weekly neuro-radiology meeting where there is clinical correlation done between the stroke team and a fellowship trained neuro-radiologist (MA) who interprets the brain imaging. This correlation is crucial in defining the presence of either symptomatic intracranial haemorrhage or haemorrhagic transformation, as well as determining if a mimic had been thrombolysed. For consistency, the definition of a symptomatic intracranial haemorrhage is a haemorrhage post-tPA administration, resulting in a significant clinical decline as demonstrated by a four-point or more increase in the National Institute of Health Stroke Scale (NIHSS) and where in the opinion of the neuro-radiologist and the treating stroke team, the deterioration was due to the bleed as opposed to the size of the infarct. This definition is derived from the previously published ECASS-3 study.10 Data from each thrombolysis case, such as demographic details, door-to-needle time, the pre- and posttPA NIHSS, complications and discharge destination are maintained prospectively by a nurse practice consultant (MB). The post-tPA NIHSS is performed on the first day post-thrombolysis as part of the tPA protocol delivery. For the purpose of analysis, data were extracted from this database and combined with clinical and imaging data and imputed into a statistical software package by a research resident not involved in the clinical care of the patient (AG). Analysis was carried out by AL and verified by a separate clinician not involved in the care of stroke patients (CC) in order to minimise observer bias.
Statistical analysis This was carried out on Stata 9.2 (Statacorp, College Station, TX, USA). Continuous variables are described as a mean ± standard deviation (SD), while dichotomous are described as an absolute number with a percentage in parentheses. For the purpose of hypothesis testing, the data were separated into two cohorts, those patients undergoing thrombolysis under the care of the stroke neurologist versus those undergoing thrombolysis under a stroke physician. A student’s t-test was used for comparison of continuous variables, and Fisher’s exact test was used for comparison of dichotomous variables. An alpha of 0.05 was considered statistically significant. © 2014 Royal Australasian College of Physicians
306
Stroke thrombolysis
Table 1 Demographic details of subjects Demographics (n = 49) Age (years) Gender (male) Door to needle time (min) NIHSS pre-tPA NIHSS post-tPA
76 ± 16 54% 104 ± 40 10 ± 1 5±1
NIHSS, National Institute of Health Stroke Scale; tPA, tissue plasminogen activator.
present, but without symptomatic intracranial bleeding, defined by the presence of an increase of the NIHSS of four or more. In one subject, a spontaneous subdural haematoma was observed (Fig. 1; subject 6). In five of the six subjects, there was a reduction in the NIHSS between the pre- and post-tPA scores. There was one death recorded in this group (subject ID 1), the cause of death being aspiration pneumonia. Individual characteristics of these subjects are listed in Table 3. During this period, there were no stroke mimics thrombolysed.
Results
Discussion
Forty-nine subjects underwent thrombolysis in the calendar year 1 January 2013 to 31 December 2013 with 54% male and the mean age of subjects being 76 ± 16 years. The age of subjects ranged from 38 to 92 years. Forty-seven of the 49 patients underwent CT perfusion imaging. The mean door-to-needle time was 104 ± 40 min with a range of 47–213 min (Table 1). Even in the two subjects where perfusion was not done, their doorto-needle time of 65 min and 87 min, respectively, was not significantly shorter than those who had perfusion scanning. Using a paired t-test, there was a statistically significant reduction in the NIHSS by 5 ± 1 points from a mean NIHSS prior to tPA of 10 ± 1 to a mean of 5 ± 1 post-tPA (P < 0.000, t = 6.6, df = 40) for all subjects (Table 1). Twenty-one subjects (43%) were thrombolysed by a stroke neurologist, while the remaining were thrombolysed by stroke physicians. There was no statistical difference between the mean door-to-needle time, proportion of individuals with haemorrhagic transformation or the discharge destination between the two groups (Table 2). Forty-three subjects (87%) had no evidence of intracranial haemorrhage on CT brain scan 24 h post-tPA infusion. In five patients, haemorrhagic transformation was
Although stroke is the second largest killer behind heart disease and the number one cause of disability in many countries, the number of neurologists available to deal with the disease burden is limited. In some parts of the world, such as the United Kingdom, non-neurologists who have had specific training in stroke, termed stroke physicians, are involved in stroke care. Controversy exists regarding this model. Opponents point out that the neurologist is best suited to stroke care by virtue of their training and expected superior diagnostic skills.6 Proponents point out that the major advance in stroke care, the stroke unit, was designed by a nonneurologist and that a large amount of stroke care postdiagnosis involves secondary prevention.5 It has been pointed out that rather than stroke being the province of one or the other, combining the skills of both may result in a better outcome.11 There is evidence to suggest that when comparing the stroke neurologist to the general neurologist, the stroke neurologist has the better patient outcome.8 To date there has been no direct comparison between stroke physician and stroke neurologist in any facet of stroke care. As thrombolysis is based on a systems approach and modern brain imaging with perfusion-weighted imaging can aid in the selection of the stroke patient from
Table 2 Characteristics of subjects thrombolysed by either a stroke neurologist or stroke physician Stroke neurologist (number lysed = 21) Door-to-needle time (min) Symptomatic intracranial haemorrhage (%) Number of haemorrhagic transformation (%) Discharge destination Rehab at home Died Home Rehabilitation Nursing home
Stroke physician (number lysed = 28)
P-value
109 ± 1 0 2 (10%)
99 ± 8 0 4 (14%)
0.43 0.69
2 (10%) 2 (10%) 7 (33%) 8 (38%) 2 (10%)
0 (0) 2 (7%) 12 (43%) 13 (46%) 1 (4%)
0.48
© 2014 Royal Australasian College of Physicians
307
Lee et al.
Figure 1 Plain computer tomography brain scans post-tissue plasminogen activator administrations demonstrating haemorrhagic transformation in subjects 1–5, with subject 6 having a left hemisphere subdural haematoma.
the mimic, we hypothesised that there should be no difference in the outcomes between those lysed by a stroke neurologist versus a non-neurologist stroke physician. Our results tend to support this hypothesis as there was no difference in the proportion of individuals with haemorrhagic transformation, the discharge destination or door-to-needle time. Most importantly, there were no symptomatic intracranial haemorrhages post-tPA. On the contrary, there was a net benefit of tPA with a reduction of the mean NIHSS between pre- and post-tPA phases. While this result could be due to chance, we also believe that careful patient selection using advanced multi-modal imaging had a role to play. The final results of the START-EXTEND trial will be valuable in this regard.12 Nevertheless, these findings should be interpreted with caution due to some inherent internal study biases. First, this is an unblinded, observational study arising from a single-stroke centre. Even though the data extractor was not involved in the clinical care of the
patient, and there was a second person to perform the data analysis and the adjudication of patient outcomes occurred as a consensus during weekly neuroradiology meetings, it cannot be denied that all members of the research team come from the same institution. Thus, our result of equivalence could be a function of observer bias. Second, while this is a study of subjects thrombolysed in a calendar year, the sample size of 49 is relatively small, especially when dichotomising the group between those thrombolysed by a neurologist versus a stroke physician. For example, the acceptable proportion of intracranial haemorrhage would now be of the order of 1–2%. Therefore, to demonstrate a signal for harm would require a sample size in the order of 100–200 subjects. Our group intends to continue collecting data over the next 2–3 years, and a subsequent publication will demonstrate if our original hypothesis was true. Third, there is clearly an imbalance between the singlestroke neurologists versus three-stroke physicians.
Table 3 Characteristics of subjects who developed post-tPA bleeding ID
Age (years)
Gender
Physician
NIHSS pre-tPA
NIHSS post-tPA
Outcome
1 2 3 4 5 6
76 85 90 76 88 91
F F F M F M
Stroke physician Stroke physician Stroke neurologist Stroke physician Stroke neurologist Stroke physician
22 10 21 16 11 19
17 8 19 2 8 22
Dead Rehabilitation Nursing home Home Rehabilitation Rehabilitation
Subject numbers correspond with those on Figure 1. NIHSS, National Institute of Health Stroke Scale; tPA, tissue plasminogen activator. © 2014 Royal Australasian College of Physicians
308
Stroke thrombolysis
However, such an imbalance weighs the result in favour of finding the alternative hypothesis is true, or that there is a difference between stroke neurologists and stroke physicians. This was not the case. Nevertheless, our study provides valuable information on the question of equivalence of the stroke neurologist versus the stroke physician in thrombolysis. In the context of a stroke centre where there is a set protocol for thrombolysis delivery, coupled with a mentored-training programme for thrombolysis and the ready availability of perfusion imaging, there is no signal for harm if thrombolysis is delivered by a trained non-neurologist stroke physician. Our data should therefore be seen in the light of a hypothesis-generating study asking the question, is it the system or the physician that delivers the outcome in thrombolysis? One method of resolving this question would be to construct a cluster randomised trial of thrombolysis-naïve hospitals and having them staffed with either a group of stroke neurologists or a group of
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stroke physicians, accompanied by a standard protocol for lysis. Such a study design could answer the question, but the logistics of randomising staff would be fraught with difficulties to say the least. An alternative would be to incorporate the speciality of origin of the physician delivering thrombolysis into existing thrombolysis registries and capturing data on the presence or absence of various components of a thrombolysis protocol. A key part of either the registry or the cluster randomised controlled trial would be the presence of an independent outcomes adjudication committee, which would remove the risk of observer bias.
Conclusion Our study demonstrates no difference in outcomes between thrombolysis delivered by a stroke neurologist versus a stroke physician, but it requires further hypothesis testing before a final conclusion can be made.
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