Article Text
Abstract
Background The off-hour effect has been observed in the medical care of acute ischemic stroke. However, it remains unclear if time of arrival affects revascularization rates and outcomes after endovascular therapy (EVT) for emergent large vessel occlusion (ELVO). We aimed to investigate the clinical outcomes of EVT between on-hour and off-hour admissions.
Methods Patients who underwent EVT for ELVO from January 2013 to June 2019 from the STAR Registry were included. Patients were grouped based on time of groin puncture: on-hour period (Monday through Friday, 7:00 am–4:59 pm) and off-hour period (overnight 5:00pm–6:59am and the weekends). Primary outcome was final modified Rankin Scale (mRS) at 90 days on mRS-shift analysis.
Results A total of 1919 patients were included in the study from six centers. The majority of patients (1169, 60.9%) of patients presented during the off-hour period. The mean age was 68.1 years and 50.5% were women. Successful reperfusion, as defined by a Thrombolysis In Cerebral Infarction (TICI) score of ≥2B, was achieved in 88.8% in the on-hour group and 88.0% in the off-hour group. Good clinical outcome (mRS 0–2) was obtained in 34.4% of off-hour patients and 37.7% of on-hour patients. On multivariable ordinal logistic regression analysis, time of presentation was not associated with worsened outcome (OR 1.150; 95% CI 0.96 to 1.37; P=0.122). Age, admission National Institutes of Health Stroke Scale (NIHSS), baseline mRS, and final TICI score were significantly associated with worse outcomes.
Conclusion There is no statistical difference in functional outcome in acute ischemic stroke patients who underwent EVT during on-hours versus off-hours.
- stroke
- thrombectomy
- intervention
Data availability statement
All data relevant to the study are included in the article.
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Introduction
The weekend effect or ‘off-hours’ effect is a well-documented phenomenon across a variety of medical specialties.1 2 Epidemiological studies have also identified this off-hours effect in stroke care, observing that patients with acute ischemic stroke admitted on the weekends experienced poorer functional outcomes and higher mortality rates.3–5 It has been hypothesized that this could be due to decreased in-hospital resources, disparity in expertise and standardized care, and lack of availability of specialists and procedures during the weekends.3
Endovascular therapy (EVT) has become the mainstay of treatment for acute ischemic stroke due to emergent large vessel occlusions (ELVO).6–10 Timely revascularization of penumbra is associated with better functional outcomes,7 driving efforts to ameliorate any delays in reperfusion. Among the key factors affecting the ability for timely reperfusion is time to presentation. Data on the effect of time of presentation on procedural and functional outcomes are limited, and the existing results have been conflicting. In a nationwide retrospective review of 12 000 patients, thrombectomy patients admitted on the weekends experienced worse outcomes in non-teaching hospitals, but there was no significant difference in outcomes for teaching hospitals.11 Another single-center retrospective review of thrombectomy cases performed at a comprehensive stroke center showed worse functional outcomes when EVT was performed during the off-hours.12 Other studies have shown that although there were delays in door-to-reperfusion timings for patients admitted during nighttime and weekends, there was no statistically significant difference in functional outcomes when comparing on-hour versus off-hour admissions.13–15 This study aimed to elucidate the effect of off-hour endovascular stroke interventions on functional outcome.
Methods
Setting
A retrospective analysis was performed to evaluate the effect of ‘on’ versus ‘off’ hour presentation on thrombectomy outcomes using patient data from the multicenter STAR Registry database. The STAR Registry is an ongoing, prospective, observational database of 11 centers in the United States (US) that perform EVT in patients with acute ischemic stroke. Six comprehensive stroke centers that participate in this registry provided consecutive patients who received EVT for anterior and posterior circulation ELVO from January 2013 to June 2019. All patients who received thrombectomy had evidence of ELVO on cerebrovascular imaging and underwent attempted mechanical thrombectomy. Among the six centers, the mean number of neurointerventionists participating in call at each center was three in 2013–2016 and four in 2017–2019; the average number of hospitals covered on call per center was two across all study years. Data for the registry was obtained retrospectively and provided without core laboratory adjudication to the primary center by researchers at each individual participating center.
The following data were collected from this registry: demographics, National Institutes of Health Stroke Scale (NIHSS) at time of presentation, baseline modified Rankin Scale (mRS), intravenous tissue plasminogen activator (IV tPA) usage, Alberta Stroke Program Early CT Score (ASPECTS) on admission computed tomography (CT), time of symptom onset and recanalization, day of week and time of vascular access, final Thrombolysis In Cerebral Infarction (TICI) score, post-procedural hemorrhagic transformation, and last known mRS.
Dichotomization into ‘on-hour’ versus ‘off-hour’ presentation was determined based on time of groin puncture. The on-hour period was defined as Monday–Friday from 7:00 am to 4:59 pm. Off-hours were defined as 5:00 pm to 6:59 am on weekday nights (Monday, Tuesday, Wednesday, and Thursday until Friday at 07:00 am) and Friday 5:00 pm through Monday 6:59 am on weekends. Proximal anterior circulation was defined as the intracranial internal carotid artery (ICA), M1 segment of the middle cerebral artery (MCA), and A1 segment of the anterior cerebral artery (ACA). Distal anterior circulation was defined M2, M3, or M4 branches of the MCA or distal ACA branches.
Statistical analysis
The primary outcome was defined as the common odds ratio (OR) for a shift in direction of poorer final mRS based on time and day of treatment. Multivariable ordinal logistic regression was used to estimate the ratio using only day and time of treatment as the predictor (unadjusted) and then again by adding several covariates (adjusted). In order to assess the assumption of proportionality of odds, all ORs were calculated at each cut-off on the scale to ensure consistency of the overall effect. No imputation of missing covariates was made. If final mRS was missing, it was imputed with 90-day mRS. The adjusted model included time and date of treatment dichotomized (on/off), age, admission NIHSS, baseline mRS, TICI score dichotomized as good (>2B) versus bad, and four categories of occluded vessel. Vessel occlusion was categorized thus: cervical ICA, proximal anterior circulation (intracranial ICA, M1, and A1), distal anterior circulation (M2, A2, and beyond), and posterior circulation. Other variables did not affect mRS and did not improve model fit. These variables were therefore excluded: hospital site, year, sex, ASPECTS score, and hemorrhagic transformation. ORs are reported with 95% confidence intervals (CIs). Descriptive statistics were calculated such that mean (SD) were used for normally distributed variables and median (range) for nonparametric data. Two-tailed hypothesis testing was used with P<0.05 interpreted for statistical significance. All analyses were conducted using R: A language and environment for statistical computing (Version 3.6.1; R Foundation for Statistical Computing, Vienna Austria) and RStudio: Integrated Development for R (Version 1.1.456; RStudio, Inc., Boston, MA, USA).
Results
Baseline characteristics
A total of 1919 patients underwent EVT during the study period. The mean age of the entire cohort was 68.1 years and 50.5% were women. The mean admission NIHSS was 15.9±7.1, and 63.5% of patients had a baseline ASPECTS score ≥6. The majority of included patients were treated during or after the year 2015 (n=1765, 92%).
After imputation of our primary outcome variable of last mRS, there were a total of 1857 cases for analysis in the unadjusted model. A minority of patients (721; 38.8%) underwent EVT during the defined on-hour period and 1136 patients (61.2%) during the off-hour period. Table 1 shows the characteristics of the two groups. There was a statistically significant difference between the two groups in baseline mRS (P=0.046). A total of 47.6% of patients in the off-hour group received IV tPA compared with 41.8% of patients in the on-hour group (P=0.018). Successful reperfusion, as defined by a TICI score ≥2B, occurred in 88.8% in the on-hour group and 88.0% in the off-hour group (P=0.663).
Primary outcome
Good clinical outcome (mRS 0–2) was obtained in 34.4% of off-hour patients and 37.7% of on-hour patients. In the unadjusted model of 1857 patients, a common OR (95% CI) for day and time of treatment was 1.076 (0.904, 1.281; P=0.41) (figure 1A).
When adjusting for missing data for predictor variables, the final number of patients for the adjusted model was 1676 with 656 patients treated during the on-hour period and 1020 treated in the off-hour period. The common OR (95% CI) for the predictor day and time was 1.150 (0.963, 1.373), which was not statistically significant (P=0.122) (figure 1B).
Secondary outcomes
All secondary outcomes, including age, admission NIHSS, baseline mRS, final TICI score, and posterior circulation occlusion were significantly associated with final mRS (table 2). Unsuccessful reperfusion (TICI score ≤2A) was strongly associated with poor outcome (OR (95% CI) 3.256 (2.433, 4.357); P<0.001). Posterior circulation ELVO was also associated with worse outcome than the ICA reference group (OR (95% CI) 1.450 (1.017, 2.069); P=0.04).
Time of procedural start
Procedural times, as defined by time from groin puncture to groin closure, were collected for all 1857 patients. figure 2 illustrates the distribution of procedural times, with peak number of procedures occurring in the early off-hour period.
DISCUSSION
This is the largest multicenter study to date containing individual patient clinical data points and reporting on the relationship between time of EVT for ELVO on long-term outcomes, including over 1900 patients treated at six different US comprehensive stroke centers. This study demonstrates no significant effect of on- versus off-hour presentation on functional outcomes and no relationship between time of procedure and reperfusion, procedural length, length of stay, or hemorrhagic transformation.
A potential deleterious effect on EVT outcomes with off-hour presentation could be presumed as a result of a number of potential factors. For example, procedural staff often must commute from home for off-hours presentations, which may contribute to longer door-to-puncture times. Procedural length may be increased related to off-hours staff having less familiarity with EVT procedures or who have other call responsibilities. Also, physician or staff fatigue during late-night procedures may cloud judgment or increase risk of procedural complications. When considering other stroke types, contradiction also exists regarding the ‘off-hour effect’ on outcomes. A nationwide review of intracerebral hemorrhage admissions revealed an association between weekend admission and increased risk-adjusted mortality.16 Conversely, a nationwide retrospective review of subarachnoid hemorrhage admissions showed that there was no significantly increased risk of short-term mortality for weekend admissions.17 In other medical conditions, weekend admissions have been shown to have a negative effect on clinical outcomes, demonstrated by longer lengths of stay likely due to factors related to limited weekend staffing, including varying physician coverage, slower progression out of the intensive care unit, and delayed determination of rehabilitation needs.18–21
There has been conflicting evidence regarding the presence of an ‘off-hour effect’ on outcomes in stroke care. Almallouhi et al reported worse outcomes for mechanical thrombectomy performed during off-hours in comparison to thrombectomy procedures performed during business hours.12 Saad et al performed a nationwide review of 12 000 patients undergoing EVT and found that patients admitted during the weekend experienced worse outcomes in non-teaching hospitals, but no statistical difference in outcomes were found for teaching hospitals.11 This study was limited by the inability to capture patient-specific stroke data such as NIHSS, site of occlusion, or 90-day outcome data, limiting the utility of its conclusions.
Kim et al, in a South Korean registry study including over 1500 patients, demonstrated no difference in outcomes between on- and off-hour presentation.22 This study featured patients treated between 2010 and 2015, with most treated prior to EVT becoming the standard of care treatment for ELVO, at predominantly lower volume hospitals (majority with annual procedural volume of less than 60 per year) and its results may not be generalizable to modern thrombectomy practice. The largest single-center US study to date evaluating the effect of presentation time on outcomes after EVT was Almallouhi et al with a total sample size of 196 patients across a single comprehensive stroke center,12 which may be underpowered to detect small beneficial effects or identify factors that contribute to poor outcomes during off-hour admissions. This present study, featuring data from nearly 2000 patients from six disparate higher volume US centers with 92% of patients treated during or after 2015, is unlikely to suffer from these limitations. The conclusions of this study are consistent with other published data demonstrating a lack of ‘off-hour effect’ in comprehensive stroke centers.11 13–15 23 Most notably, the present study strongly suggests the absence of a weekend or off-hour effect on successful reperfusion, procedural length, hemorrhagic transformation, length of stay, or clinical outcomes. The present study provides further evidence that in comprehensive stroke centers with robust systems of care including integrated neurointerventional surgery, stroke neurology, intensive care unit, and rehabilitation teams, potential deleterious consequences on outcomes with off-hour presentation can be successfully mitigated.
Previous studies have demonstrated a temporal fluctuation in EVT presentations, with peak procedural incidence occurring between 3 pm and 5 pm, a second peak between 11 am and 1 pm, and a third smaller peak between 8 pm and 10 pm.24–26 In the present study, peak procedural incidence occurred between 5 pm and 6 pm, with a second peak occurring between 7 pm and 8 pm. These incidence curves again suggest that the peak time for EVT procedures is during ‘off’ hours at 6–8 pm, a finding with important implications for stroke call and personnel coverage.
An additional notable finding from this study pertains to intravenous tPA utilization. There was a significantly higher utilization of intravenous tPA during off-hour (48%) compared with on-hour (42%; P=0.018), yet differences in tPA utilization did not translate to differences in clinical outcomes. While recent publications suggest that intravenous tPA use may improve thrombectomy revascularization attempts,27 others have argued no benefit to clinical outcomes compared with thrombectomy alone28 but with higher hospital costs.29 Although the present study was not designed to study differences in tPA utilization or its effect on outcomes, no observable relationship was found between the use of tPA and revascularization success or clinical outcomes.
There are limitations to this study, most notably its retrospective nature and lack of core laboratory adjudication of imaging, procedural, or clinical outcomes, which is known to lead to overestimation of the percentage of good outcomes.30 Additionally there is the potential for selection bias and an inability to ensure all treated patients at each participating center are included in the registry. The study was performed at six urban comprehensive stroke centers, and therefore the results may not be generalizable to thrombectomy-capable stroke centers or community hospitals. Missing data points were present, most notably ASPECTs scores. There is no standard definition for on- versus off-hour dichotomization based on time of day. We therefore defined ‘on-hour’ based on a 7:oo am to 5:00 pm workday as utilized by most study centers that initiate elective cases at or shortly after 7:00 am with call staff assuming responsibilities at 5:00 pm. As such, these data may not be wholly generalizable to other centers with different work schedules or that offer elective weekend endovascular procedures. Finally, the study also did not account for holidays, which should be considered off-hour, but in the majority of cases (5 of 7 days), daytime procedures occurring on holidays were included among on-hour procedures.
Conclusions
This is the largest multicenter study to date containing individual patient clinical data points and reporting on the relationship between time of EVT for ELVO on long-term outcomes, including almost 2000 patients treated at six different US comprehensive stroke centers. There is no demonstrable effect of on- versus off-hour procedural time on functional outcomes, successful reperfusion, procedural length, length of stay, or hemorrhagic transformation.
Data availability statement
All data relevant to the study are included in the article.
Ethics statements
Ethics approval
IRB approval obtained at each participating center. Primary center: Institutional Review Board for Human Research at the Medical University of South Carolina: IRB # Pro00090704.
References
Footnotes
Collaborators On behalf of the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators: Christine Tschoe, MD (1); Carol Kittel, MA, (2); Patrick Brown, MD,(1,3); Anthony Anzalone, MS (1); Colton Smith, BA (1); Trent VanHorn, BA (1); Muhammad Hafeez, MD (4); Peter Kan, MD (4); Ali Alawieh, MD (5); Sami Al Kasab, MD (5); Jonathan Lena, MD (5); Kimberly Kicielinski, MD (5); Alejandro M Spiotta, MD (5); Eyad Almallouhi, MD (6); Travis M Dumont, MD (7); David J McCarthy, MSc (8); Robert M Starke, MD (8); Christopher Kellner, MD (9) Johanna Fifi, MD (9); Reade De Leacy, MD (9); Stacey Q Wolfe, MD (1); Kyle M Fargen, MD (1). Institutions: (1) Department of Neurological Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; (2) Division of Public Health Sciences, Department of Biostatistics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; (3) Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; (4) Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA; (5) Department of Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA; (6) Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA; (7) Department of Neurosurgery, University of Arizona, Tucson, Arizona, USA; (8) Department of Neurological Surgery and Neuroradiology, University of Miami, Miami, Florida, USA; (9) Department of Neurosurgery, Mount Sinai Health System, New York City, New York, USA.
Contributors Concept design: KMF, AMS, SQW. Manuscript composition: CT, KMF, AMS, SQW, PB, CK. Data collection: all authors. Statistical analysis: CK. Final approval of article: all authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.