(Stroke. 1999;30:40-48.)
© 1999 American Heart Association, Inc.
Original Contributions |
From the Department of Medicine, University of Umeå (P.W., M.P.); Department of Neurology, University of Linköping (J.R.); and Janssen-Cilag AB, Västra Frölunda, Sweden (B.L.).
Correspondence to Per Wester, MD, PhD, Umeå Stroke Center, Research Laboratory, 5B Department of Medicine, University Hospital of Umeå, S-901 87 Umeå, Sweden. E-mail per.wester{at}medicin.umu.se
| Abstract |
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MethodsThis was a prospective, multicenter, consecutive study that explored factors influencing the time from stroke or transient ischemic attack (TIA) onset until patient arrival at the emergency department, stroke unit, and CT laboratory. Within 3 days of hospital admission, the patients and/or their relatives were interviewed by use of a standardized structured protocol, and the patients' neurological deficits were assessed. No information about this study was given to the public or to the staff.
ResultsPatients (n=329) were studied at 15 Swedish academic or community-based hospitals: 252 subjects with brain infarct, 18 with intracerebral hemorrhage, and 59 with TIA. Among stroke and TIA patients, the median times from onset to hospital admission, stroke unit, and CT scan laboratory were 4.8 and 4.0 hours, 8.8 and 7.5 hours, and 22.0 and 17.5 hours, respectively. From multivariate ANOVA with logarithmically transformed time for increasing delay to hospital admission as the dependent variable, a profile of significant risk factors was obtained. This included patients with a brain infarct, gradual onset, mild neurological symptoms, patients who were alone and did not contact anybody when symptoms occurred, patients who lived in a large catchment area, those who did not use ambulance transportation, and those who visited a primary care site. These factors explained 45.3% of the variance in delayed hospital admission. The median time from arrival at the emergency department to arrival at the stroke unit or CT scan laboratory (whichever occurred first) was 2.6 and 2.7 hours in the stroke and TIA groups, respectively. A large catchment area, moderate to mild neurological deficit, and waiting for the physician at the emergency department were all significantly related to in-hospital delay.
ConclusionsIncreased public awareness of the need to seek medical or other attention promptly after stroke onset, to use an ambulance with direct transportation to the acute-care hospital, and to have more effective in-hospital organization will be required for effective acute treatment options to be available to stroke patients.
Key Words: cerebrovascular disorders hospitalization stroke management stroke onset emergency service, hospital
| Introduction |
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In recent years, there have been several studies of time from stroke ictus to arrival at hospital,7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 with somewhat limited and conflicting results. This may be due to different study designs: most studied only patients at a single hospital and explored only a few variables. Some studies were retrospective, some did not consider patients with a hospital arrival beyond 24 or 48 hours after symptom onset, and some only considered patients transported to the hospital by ambulance. There were also differences in interpreting nocturnal onset of stroke.
Prospective, multicenter studies on referral patterns in stroke victims based on both academic and community-based hospitals with differences in geographic and catchment-area sizes have not been reported previously. In addition, there are no such reports on patients with transient ischemic attacks (TIAs), who during the first few hours of onset of focal neurological deficits may be impossible to differentiate from stroke patients.22 The aim of the present study was to assess the time between stroke/TIA onset and clinical and radiological diagnoses and to explore in detail the factors associated with any related delays.
| Subjects and Methods |
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20 patients or when the total
number of patients included was >300. At each stroke center, all
patients arriving at the emergency department, including those with an
initial suspicion of stroke or TIA (as judged by the emergency
ward nurses, who were not aware of this study) were recorded daily in a
logbook by the study nurses. The number of these patients who were
hospitalized was also recorded. Within 3 days of hospital admission,
the stroke study nurses or doctors contacted in-patients in whom an
initial suspicion of stroke or TIA had been raised, and patients who
fulfilled the study entry criteria were asked to participate in the
study. A structured interview with the patient or relative was made
within 3 days of hospital admission. Barthel's Activities of Daily
Living (ADL) function23 before the present illness was
estimated, and a European Stroke Scale (ESS) assessment24
was performed as an estimate of stroke severity. The ESS ranges from 0
(worst clinical status) to 100 (without any symptoms), and thus a score
of 70 indicates a mild and 30 a severe degree of stroke-related
symptoms. The final diagnoses were recorded when the patients were
discharged. Time of stroke or TIA onset was defined as the time the
patient or an observer first noted a neurological deficit. Patients who
had their first symptoms during the night were divided into 1 group in
whom symptoms occurred while awake and another group who noticed the
symptoms upon awakening; this latter group was analyzed
separately.
For patient characteristics, means (or median), number, and proportions
are presented. To test for difference in proportions between
the diagnostic groups, the
2 test
was used. Owing to skewed distribution of the time variables, the
Mann-Whitney U test and Kruskal-Wallis 1-way ANOVA were used
for univariate analysis. For
multivariate analysis of time delay, ANOVA with
covariates was used, with logarithmically transformed time delay as the
dependent variable. The cumulative rates of patients admitted to
the emergency departments and stroke unit or CT scan laboratory at
various times were examined with log-rank survival analysis to
test for differences between diagnostic groups. Because
different routines were applied at the participating hospitals
regarding whether patients were transported to the stroke unit (or its
equivalent) or to the CT scan laboratory after arriving at the
emergency department, the time until the first occurrence of these
events was calculated as in-hospital delay. Two-tailed significance was
used, and a probability value of 0.05 was considered significant in the
univariate and multivariate
analyses. Analyses were performed with the statistics
package SPSS version 6.1.25
| Results |
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Patient Characteristics
The characteristics of the 329 eligible stroke and TIA patients
are presented in Table 1
.
Six percent of the patients had intracerebral
hemorrhage (ICH), and 18% had TIA. The mean age for the entire
group of patients was 73.1 years, with TIA and ICH patients being
somewhat younger than infarct patients (P<0.05 by
Kruskal-Wallis ANOVA). In the total study group, 21% and 9% had had a
previous stroke or TIA, respectively. Thirty-nine percent had a
diagnosis of hypertension, 19% angina pectoris, 14% atrial
fibrillation, 12% heart failure, and 18% diabetes mellitus. Four
percent of patients had been unconscious from symptom onset, whereas
41% and 70% of the patients reported speech disturbance and
paresis as initial symptoms, respectively. Most of the patients
experienced symptom onset at home, and 51% were transported to the
hospital by ambulance. The time, as estimated by the patient or a
bystander, for the ambulance to arrive after having been called was 10
to 15 minutes. The majority of patients were independent in ADL before
the current disorder according to the Barthel index. The neurological
deficit, as measured by the ESS immediately after the interview,
differed between diagnostic groups: most TIA patients had
no disturbance, brain infarction patients were generally
moderately injured (mean ESS value of 78), and the ICH group showed the
most severe stroke symptoms (mean ESS of 61). A CT scan had been
performed at time of interview in 92% of the study population.
Estimates by the patient or bystander at time of interview of the time
elapsed from arrival at the emergency department to first examination
by a doctor revealed that in 42% of all patients, >1 hour had elapsed
(Table 1
).
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Duration From Symptom Onset to Arrival at Hospital, Stroke Unit,
and CT Scan Laboratory
In the Figure
(panels A and B), the time from
symptom onset to arrival at an emergency department is shown. There was
a significant difference between the diagnostic groups,
with the shortest time elapsing in the ICH group (median, 1.7 hours),
followed by TIA (median, 4.0 hours) and brain infarction patients
(median, 5.1 hour) (P<0.01 by log-rank survival
analysis and P<0.01 by Kruskal-Wallis ANOVA). Much
of this delay was due to the time between symptom onset and the
patient's first call for help (panel B), which was to a
relative/acquaintance or staff at the emergency 112 call system, a
primary care unit, or a hospital. Hence, the median time to call for
first help was 0.5, 2.2, and 3.4 hours among ICH, TIA, and infarct
patients, respectively (panel B), accounting for 32%, 55%, and
68% of the time from symptom onset to arrival at the emergency
department. The median time from symptom onset to arrival at a stroke
unit or equivalent was 8.8 hours among stroke patients and 7.5 hours in
the TIA group. The median time from symptom onset to arrival at a CT
scan laboratory was 22.0 and 17.5 hours among stroke and TIA patients,
respectively. The median time from arrival at the emergency department
to arrival at the stroke unit/team or CT scan laboratory was 2.8 and
2.9 hours or 7.0 and 7.4 hours in the stroke and TIA groups,
respectively. As shown in the Figure
(panel C), the median time
from arrival at the emergency department to arrival at the stroke unit
or arrival at the CT scan laboratory (whichever occurred first) was 2.7
and 2.3 hours among infarct and hemorrhagic stroke patients,
respectively, and 2.7 hours in the TIA group (P>0.2 by
log-rank survival analysis).
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Factors Related to Increased Time From Symptom Onset to Hospital
Admission: Univariate Analysis
Age, sex, previous TIA, previous ADL function according to
Barthel's index, marital status (alone or married/cohabiting), way of
living (alone in own house, with relative in own house, in service
house for the elderly or disabled, or other), level of consciousness,
presence of paresis, and time of day that first symptoms appeared had
no significant impact on the time from symptom onset to hospital
admission (data not shown). Previous stroke, speech
disturbance, and sudden onset of initial symptoms were related
to decreased time delay among stroke patients (Table 2
; P<0.01 to
P<0.001 by Mann-Whitney U test). Fluctuating
symptoms before arrival at hospital in stroke and TIA patients and mild
neurological symptoms according to the ESS score, as well as being
alone when symptoms first occurred among stroke patients, were each
associated with increased time to hospital admission
(P<0.05 to P<0.001 by Kruskal-Wallis ANOVA and
P<0.01 by Mann Whitney U test). If the first
symptoms were not recognized as stroke related (which was the case
among 44% of stroke and 48% of TIA subjects), or despite recognition
of symptoms as stroke related, patients actively chose not to seek any
help within 1 hour (24% of stroke and 20% of TIA patients), time to
hospital admission was increased (P<0.001 by Kruskal-Wallis
ANOVA). Stroke and TIA patients who contacted a relative, hospital, or
family doctor as a first action after symptom onset had a substantially
shorter time to hospital admission than patients who waited (Table 2
; P<0.001 by Kruskal-Wallis ANOVA). Among stroke
patients not seeking any help within 1 hour, subjects who were not
aware of initial symptoms or thought symptoms would disappear, as well
as patients who had similar symptoms before that disappeared, had an
increased time to hospital admission compared with patients who were
unable to call for any help within 1 hour of symptom onset (Table 2
; P<0.01). In the stroke group, living in a
catchment area of >200 000 inhabitants was associated with increased
time to hospital admission (P<0.01 by Kruskal-Wallis
ANOVA), whereas the distance between the place where the initial
symptoms occurred and the hospital did not influence the time to
hospital admission (P>0.2). Stroke patients who were not
transported to the hospital by ambulance had a longer delay to hospital
admission (Table 2
; P<0.001), as did stroke and TIA
subjects who visited their family doctor before going to a hospital
(Table 2
; P<0.01 to 0.001 by Mann-Whitney
U test).
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Factors Related to Increased Time From Symptom Onset to Hospital
Admission: Multivariate ANOVA
All factors from the univariate
nonparametric tests as presented in Table 2
were initially included in a multivariate ANOVA model
to explain the variance of the natural logarithmic time value from
symptom onset to hospital admission. As presented in Table 3
, diagnosis, symptom onset, neurological
severity, presence of a bystander, the patient's initial reaction,
catchment-area size, mode of transportation to the emergency
department, and visit to a family doctor were all significant factors
closely related to increased time to hospital admission. With these
factors, 45.3% of the variation in the time from onset of symptoms to
hospital admission could be explained.
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Patients Who Noticed Symptoms on Awakening
Fifteen patients with brain infarct and 7 with TIA noticed their
symptoms upon awakening after a night's sleep. The median time from
onset (set at 3 AM) and arrival at hospital was 10.1 hours
among infarct patients and 9.5 hours in the TIA group. Among infarct
patients, the initial reaction was significantly associated with
increased time to hospital arrival (did nothing, median delay 43.8
hours; contacted relative, median delay 11.8 hours; contacted hospital,
median delay 8.0 hours; contacted primary care physician, median
delay 5.4 hours; P<0.05 by Kruskal-Wallis ANOVA). No other
significant relationship was observed.
Delay Between Arrival at Emergency Department and Arrival at Stroke
Unit or CT Scan Laboratory
Table 4
shows that the degree of
neurological deficit and the catchment-area size were associated with
increased in-hospital delays among stroke patients. In both stroke and
TIA patients, an increased time from arrival at the emergency
department to first examination by a physician was associated with an
increased time from arrival at the emergency department to arrival at a
stroke unit or CT scan laboratory (whichever occurred first;
P<0.05 to 0.001 by Kruskal-Wallis ANOVA). Other factors
such as age, sex, time of day of symptom onset, initial symptoms
(unconscious, speech, or paresis), and course of symptoms (regress,
stationary, progress, or fluctuating) had no significant impact on this
delay (P>0.2 by Kruskal-Wallis ANOVA and Mann-Whitney
U test).
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| Discussion |
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Because of the use of a log book in this study, the flow of patients referred to the hospitals could be studied in detail. These data show that a remarkably large proportion of hospitalized patients with an initial suspicion of stroke or TIA, as judged by the admitting nurses at the emergency departments, who were not aware that this study was being conducted, were misdiagnosed at the time of interview. This agrees with previously published data.11 A suspicion of stroke or TIA as judged by the emergency department nurses who see the patient first after admission to hospital may sometimes be raised nonspecifically for symptoms such as dizziness, vertigo, fatigue, and general weakness. In addition, 21 patients who entered the study were found at time of discharge to have diagnoses inconsistent with stroke or TIA. This shows that the diagnosis of stroke and TIA in the very acute and even subacute phase can sometimes be quite difficult to make, and extended investigations may be required to arrive at a final correct diagnosis.31
To the best of our knowledge, reports on TIA patients regarding factors
influencing time delays from symptom onset until hospital admission,
stroke unit admission, and CT scan have not been published previously.
The reasons for including TIA patients in this study were as follows.
Acute intervention in stroke must probably be initiated within the
first few hours after onset to be effective. A substantial proportion
of patients potentially eligible for such treatment strategies will
recover spontaneously from their neurological symptoms within 24 hours
and thereby be classified as TIA, although the duration of the classic
TIA is usually <30 to 60 minutes.22 Hence, it is
practically impossible to differentiate between a stroke and TIA during
the first few hours after onset. In public campaigns about increased
awareness of stroke-related symptoms and the need to go to the hospital
immediately, it will not be possible to single out information about
TIA. Furthermore, it is appropriate that patients with TIA are referred
to a hospital for a detailed evaluation, including a search for
potential differential diagnoses, acute intervention if repeated TIAs
occur, and optimum medical or surgical secondary
prophylactics. In Sweden, it is believed but not proven
that the majority of TIA patients who seek medical help are referred to
hospitals and that many of these patients are hospitalized for a few
days. However, the hospitalized TIA patients included in the
present study probably had a somewhat more severe medical condition
than a general TIA population. This could imply that some uncomplicated
TIA patients may not have sought medical help at all or were taken care
of at a primary care center only, were not hospitalized after arrival
at the emergency department, or were discharged before the structured
interview took place. However, the demographics of the TIA patients
studied here are in good agreement with previously published
epidemiological data.22 26 A general observation in the
present study was that patients with TIA had similar time to
hospital admission and similar influencing factors on elapsed time as
the ischemic stroke patients. Thus, the course of symptoms,
recognition of initial symptoms as stroke related, patient's initial
reaction when first symptoms occurred, and visit to a primary care
physician were all factors among TIA patients that had a
significant impact on increased time to hospital admission (Table 2
).
The median time between symptom onset and hospital admission was 5.1 hours in the infarct group, 1.7 hours among ICH patients, and 4.0 hours in patients with TIA. For stroke patients, this is in the same range as previously published data; median times of 3.5 to 14 hours between stroke onset and hospital admission have been reported.8 10 11 12 17 18 19 20 A direct comparison with these studies, however, is difficult because of the different study designs (some were retrospective, some did not consider patients with a hospital arrival beyond 24 or 48 hours after symptom onset, some considered only patients who were transported to the hospital by ambulance, and there were differences in interpreting nocturnal onset of symptoms). In the present study, results obtained from patients who noticed their first symptoms upon awakening were analyzed separately because the determination of time delays in those patients is very dependent on the coding of ictus. This coding could be either last time seen without symptoms,15 21 time of awakening,17 18 29 a midpoint between those times,12 19 or exclusion of these patients.20 In the present study, the coding of ictus was set at a presumed midpoint during sleep. In both stroke and TIA patients, the time lag from symptom onset to arrival at hospital, as expected, was longer than among patients whose symptom onset came while they were awake. The proportion of patients who had their first symptoms during the night (42 of 351 subjects) is in the range of the wide variation of previously published data.11 12 15 19 20 21
In general, the results from the univariate and multivariate analyses of factors related to delayed hospital admission were congruent. From the multivariate ANOVA, a profile of risk factors associated with increased time from symptom onset to arrival at the emergency department was obtained. This risk profile included patients with a diagnosis of brain infarct, gradual onset, mild neurological symptoms, patients who were alone and did not contact anybody when symptoms occurred, patients who lived in a large catchment area, patients who did not use ambulance transportation, and patients who visited a primary care site. With these factors, 45.3% of the variation of delayed hospital admission could be explained, a higher value than the 22% to 27% of explained variance reported previously.12 14 Related to this observation is the study by Jørgensen and coworkers20 predicting a hospital admission of more or less than 6 hours using a multiple logistic regression model. They found that marital status, working status, former TIA, and stroke severity could predict 69% of cases in these dichotomized time intervals. Diagnosis of brain infarct has been reported to be associated with delayed hospital admission compared with ICH in some10 18 but not all14 16 17 studies. In agreement with our data, mild stroke severity has been reported to increase the time to hospital admission,10 20 21 and a sudden onset of a stable deficit was shown to decrease this time.16 Stroke severity, as assessed in this study by the ESS immediately after the interview, within 3 days after hospital admission, may not always have represented stroke severity shortly after stroke/TIA onset, when the patient and/or bystander decided how to act. This is due to the obvious fact that the course of stroke severity changes individually over time, with most patients improving, some being stable, and others having progression of symptoms during the first days after stroke onset.32 Patients living alone were shown to have a delayed hospital admission,12 20 which agrees in part with our results showing that being alone when symptoms occurred was associated with increased time to hospital admission, although way of living had no significant impact on this time delay.
In the present study, the failure to contact anyone when symptoms occurred was, from a quantitative standpoint, the most important factor in delaying hospital admission. Hence, time from symptom onset to first call for any help accounted for 32% of the total delay in time until hospital admission in the ICH group, 55% among TIA patients, and 68% in the brain infarct group. This may be related to the fact that 44% and 48% of stroke and TIA patients in this study, respectively, did not recognize their first symptoms as stroke related, and an additional 24% and 20% of patients did not seek any help within 1 hour despite accurately recognizing their first symptoms. This is in line with recent reports on the generally poor knowledge about stroke signs, symptoms, and risk factors33 among stroke patients, their interpretation of stroke symptoms, and how these factors influence the timing of their decision to seek medical attention.29 Thus, only one fourth of stroke patients interpreted their symptoms correctly, and this knowledge was not associated with early hospital admission.29 One surprising finding in our study was that a large catchment-area size (>200 000 persons) was associated with delayed hospital admission. One plausible explanation for this finding may be that the 2 hospitals representing the largest catchment-area size are located in Stockholm, a city known to be overrepresented by old persons living alone. However, irrespective of catchment-area size, there was a similar proportion of patients who were alone when symptoms occurred in our study. Interestingly, the median delay of 11.8 hours from symptom onset to hospital arrival in this category is in good agreement with data from another Scandinavian city of similar size, ie, the Copenhagen study,20 in which a median delay of 14 hours was reported. The referral pattern, including transportation of stroke patients, has been shown to be of great importance in delayed hospital admission,12 14 17 19 29 which is in agreement with our data showing a substantially prolonged delay in patients first referred to the family doctor and in patients not using an ambulance.
The in-hospital delay, ie, time from arrival at the emergency department to arrival at stroke unit or CT scan laboratory (whichever occurred first), was 2.7 hours in our study. To the best of our knowledge, similar data have not been published previously. This time delay is not acceptable, and it should be possible to reduce this time substantially by changing the within-hospital organization, as has been suggested recently.34 Because the emergency departments were not aware of the present study being conducted, only an estimation at the time of interview could be obtained of the time from emergency department admission to first visit by a physician. As predicted, patients with an estimated time to first examination by physician of >2 hours and patients with a mild to moderate neurological deficit had a longer time from arrival at the emergency department to arrival at the stroke unit or CT scan laboratory. The implication of this observation is that a stroke physician should examine patients with a presumed stroke or TIA within a few minutes of their arrival at the emergency ward to reduce the in-hospital delay. This would also improve the accuracy of the clinical diagnosis, which can be quite difficult in the acute stage.31
In conclusion, several factors were found to be closely related to delayed hospital admission among stroke and TIA patients. A risk profile of factors was obtained that included patients with a diagnosis of brain infarct, gradual onset, mild neurological symptoms (ESS>70), who were alone and initially did not contact anybody when their symptoms occurred. Furthermore, living in a large catchment area (>200 000 persons), not using ambulance transportation, and visiting a primary care site were all related to increased time from symptom onset to arrival at the hospital. The additional in-hospital delay, ie, the delay between arrival at emergency department and arrival at the stroke unit or CT scan laboratory, was 2.7 hours, with similar duration in each of the diagnostic groups. Factors that significantly influenced this delay were degree of neurological deficit, living in a large catchment area, and time spent waiting at the emergency department for first examination by a physician. Increased public awareness of the need to seek medical or other attention promptly after stroke onset, to use an ambulance with direct transportation to the hospital, and to provide more effective in-hospital organization is required to ensure that effective acute treatment options will be available for stroke patients.
| Acknowledgments |
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| Footnotes |
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| Appendix 1 |
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Hospitals with catchment area >200 000 persons: B. Leijd, M. Anzén, P. Ring (St Göran's Hospital, Stockholm); C. Carlström, M. Zetterling (Söder Hospital, Stockholm).
Hospitals with catchment area 100 000 to 200 000 persons: L. Hermodsson, L. Offerman, M. Tählt-Johansson (Eksjö Hospital); L. Wallrup, G.-B. Birkenhag, B. Björn, A.-S. Forsberg, K. Olsson (Falun Hospital); R. Palm, K. Bernt, I. Freudenthaler, M. Granberg, M. Magnusson (Karlstad Hospital); J. Rådberg, B. Fagrell, H. Fredriksson, G. Johansson (Linköping University Hospital); B. Stahre, E. Fransson, S. Palm (Norrköping Hospital); E. Bertholds, A-C. Elgåsen, I. Nordin (Skövde Hospital); P. Wester, B. Viksten (Umeå University Hospital); H-G. Hårdemark, M. Pettersson (Uppsala, Akademiska University Hospital).
Hospitals with catchment area <100 000 persons: K. Hulter-Åsberg, I. Malefors, O. Törmänen (Enköping Hospital); C. Lundbom, M. Ivarsson (Kungälv Hospital); J. Hackéll, M. Gustafsson, A.C. Hammarsten, K. Johansson, P. Larsson, J. Thörn (Oskarshamn Hospital); S-E. Marklund, G. Ahlström, M. Lindgren, K. Ohlin (Piteå Hospital); P. Borenstein, E. Gustafsson, A. Rovinski (Skene Hospital).
Received July 9, 1998; revision received October 23, 1998; accepted October 23, 1998.
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