Disparities in care and clinical outcomes of patients exist

Transcription

1 Comprehensive Stroke Centers Overcome the Weekend Versus Weekday Gap in Stroke Treatment and Mortality James S. McKinney, MD; Yingzi Deng, MD, MS; Scott E. Kasner, MD, MSCE; John B. Kostis, MD; for the Myocardial Infarction Data Acquisition System (MIDAS 15) Study Group Background and Purpose Hospital staffing may be reduced on weekends. Prior studies of weekend disparities in stroke care have focused on in-hospital mortality with variable results. We hypothesized that 90-day mortality was higher in patients with stroke hospitalized on weekends versus weekdays, and this difference has been minimized over time by improvements in organization and delivery of stroke care. Methods We used the Myocardial Infarction Data Acquisition System administrative database, which includes data on patients discharged with a primary diagnosis of cerebral infarction from all nonfederal acute care hospitals in New Jersey between 1996 and Out-of-hospital deaths were assessed by matching MIDAS records with New Jersey death registration files. New Jersey hospitals are designated by the state as comprehensive stroke centers, primary stroke centers, or nonstroke centers. The primary outcome measure was 90-day all-cause mortality after hospital admission. Results A total of patients were admitted with a primary diagnosis of cerebral infarction during the study period. A total of 23.4% were admitted to a comprehensive stroke center, 51.5% to a primary stroke center, and 25.1% to a nonstroke center. Ninety-day mortality was greater in patients with stroke admitted on weekends compared with weekdays (17.2% versus 16.5%; P 0.002). The adjusted risk of death at 90 days was significantly greater for weekend admission (hazard ratio, 1.05; 95% CI, 1.02 to 1.09). No difference in 90-day mortality was observed for patients admitted to comprehensive stroke centers on weekends versus weekdays (hazard ratio, 1.01; 95% CI, 0.95 to 1.08). Conclusions Patients with stroke admitted on weekends to New Jersey hospitals had a significantly higher risk of death by 90 days. No such difference in mortality was observed at comprehensive stroke centers. (Stroke. 2011;42: ) Key Words: ischemic stroke stroke center thrombolysis weekend Disparities in care and clinical outcomes of patients exist between those hospitalized on weekends versus weekdays. Hospital staffing may be reduced in quantity and spectrum on weekends. This disparity has been shown to adversely affect treatment and outcomes in patients with myocardial infarctions. 1 There have been inconsistent findings in patients admitted with stroke with most studies reporting early mortality. 2 9 Canadian and Japanese studies have shown an increased risk of death and functional disability at 7 days with weekend stroke admission. 2,3,9 In-hospital mortality was increased in patients admitted on off-hours in the Get With The Guidelines Stroke database (OR, 1.09; 95% CI, 1.03 to 1.14). 4 A report of stroke mortality in Sweden over 4 decades showed an increased risk of death with weekend admission, but the authors noted that this effect diminished over time. 5 Temporal improvements in stroke care may account for this trend. A study using the Nationwide Inpatient Sample Database reported no difference in inhospital mortality between weekend and weekday admissions for patients with stroke from 2002 to Furthermore, no difference in in-hospital mortality has been observed in patients admitted to comprehensive stroke centers on weekends. 6 There are little data on longer-term outcomes of patients with stroke admitted to hospitals on the weekend versus weekday. In 2004, the State of New Jersey enacted the Stroke Center Act, which required the NJ Department of Health and Senior Services (DHSS) to designate hospitals that meet certain standards as primary stroke centers (PSCs) or comprehensive stroke centers (CSCs). The NJ DHSS began receiving applications and issued its first certification for both PSC and CSC in Further details are available through the NJ DHSS web site ( njac43g_hoslicstd.pdf). The aims of this study are 2-fold: (1) to compare 90-day mortality rates among patients admitted with acute ischemic Received December 23, 2010; final revision received March 4, 2011; accepted March 7, From The Cardiovascular Institute of New Jersey and the Departments of Neurology (J.S.M.) and Medicine (Y.D., J.B.K.), University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, NJ; and the Department of Neurology (S.E.K.), University of Pennsylvania School of Medicine, Philadelphia, PA. The online-only Data Supplement is available at Correspondence to James S. McKinney, MD, Department of Neurology, UMDNJ Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ mckinnjs@umdnj.edu 2011 American Heart Association, Inc. Stroke is available at DOI: /STROKEAHA

2 2404 Stroke September 2011 stroke on weekends and those admitted on weekdays; and (2) to determine whether any differences in mortality could be explained by temporal improvements in stroke care or stroke center designation. Methods We used information from the Myocardial Infarction Data Acquisition System (MIDAS) administrative database for this study. 1,10 12 MIDAS contains demographic and clinical data on patients discharged with a primary diagnosis of cerebral infarction (codes , , , , , , , , and of the International Classification of Diseases, 9th Revision, Clinical Modification) from all nonfederal acute care hospitals in New Jersey. The database also includes records of treatment with intravenous (IV) thrombolysis after 1998 (International Classification of Diseases, 9th Revision code 99.10). Data for the following coexisting conditions were available: hypertension, diabetes, atrial fibrillation, and chronic renal disease. We obtained data on out-ofhospital deaths by matching MIDAS records with NJ death registration files using previously validated linkage and consolidation software (The Link King). 13 Out-of-state deaths were not recorded. Outcomes were assessed by a blinded automated procedure. Study Population MIDAS included patients admitted between 1996 and 2007 with cerebral infarction as the primary reason for admission. Only the first discharge record for a patient was included. Subsequent records were excluded to avoid duplicating data or introducing bias from interhospital transfers or readmission for the same event. Patients who were admitted to federal hospitals or nursing homes or had a stroke during an admission for another diagnosis or procedure were excluded. Study Variables The primary outcome variable was all-cause mortality within 90 days of hospital admission. In-hospital and cumulative (inpatient and postdischarge) death rates at 30, 90, and 365 days were also examined. The primary independent variable was admission on weekends (Saturday, Sunday, and holidays) versus weekdays. Covariates included patient demographics, coexisting conditions, and treatment with IV thrombolysis. Measures of stroke severity were not available. Each hospital in MIDAS was categorized based on its current NJ DHSS designation as CSC, PSC, or as a nonstroke center (NSC). Statistical Analysis We examined how differences in mortality between weekend and weekday admissions have changed over time. Data for the period from 1996 to 2007 were grouped into 2-year intervals. We compared weekend and weekday admissions in terms of both in-hospital and cumulative all-cause mortality. To adjust for confounders, we used Cox proportional hazard models in comparing the risk of death associated with weekend versus weekday admissions at 90 days. Multivariable logistic regression models were used to compare treatment among hospital types accounting for the measurable confounding effects of patient demographics and coexisting conditions. Statistical significance was defined as a probability value We examined whether the difference in mortality between weekend and weekday admissions could be explained by differences in stroke care temporally by year of admission or operationally by stroke center certification. Year of admission or stroke center certification would be considered to mediate the association between weekend and weekday admission and mortality if the hazard ratio decreased when included in the hazard model. Statistical analyses were performed using SAS software. The Institutional Review Boards of the NJ DHSS and the University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School approved the study. Informed consent was not required. Table 1. Patient Demographics and Clinical Characteristics Weekend Weekday (N ) (N ) P* Age, y (mean SD) Gender: female (55.3%) (54.6%) 0.04 Race 0.03 White (76.4%) (76.2%) Black 5651 (15.1%) (15.6%) Other 3165 (8.5%) 7950 (8.2%) Payer 0.30 Commercial 4547 (12.2%) (12.3%) Medicare (67.7%) (67.9%) Medicaid 846 (2.3%) 2278 (2.4%) Self-pay 1485 (4.0%) 3611 (3.7%) HMO 5195 (13.9%) (13.8%) Comorbid conditions Hypertension (68.7%) (69.0%) 0.30 Diabetes (29.1%) (29.3%) 0.50 Atrial fibrillation 8015 (21.5%) (21.0%) 0.03 Renal disease 1759 (4.7%) 4875 (5.0%) 0.02 Congestive heart 4824 (12.9%) (12.7%) 0.30 failure Admission source Emergency (89.4%) (84.4%) department Physician referral 1972 (5.3%) 9639 (9.9%) Transfer 1175 (3.2%) 3352 (3.5%) Other 816 (2.2%) 2206 (2.3%) Stroke center designation CSC 8952 (24.0%) (23.1%) PSC (51.8%) (51.4%) NSC 9055 (24.3%) (25.4%) Procedures IV tpa 605 (1.6%) 1299 (1.3%) Cerebral 2780 (7.5%) 7085 (7.3%) 0.30 arteriography Carotid 316 (0.9%) 1074 (1.1%) endarterectomy Length of stay (mean SD) HMO indicates health maintenance organization; CSC, comprehensive stroke center; PSC, primary stroke center; NSC, nonstroke center; IV tpa, intravenous tissue-type plasminogen activator; SD, standard deviation. *P values are based on 2 tests for categorical variables and t tests for continuous variables. Results Patient Characteristics There were patients admitted between 1996 and 2007 with a primary diagnosis of cerebral infarction with 27.8% admitted on weekends. Baseline patient demographics were similar (Table 1). There was a 27.9% decline in stroke admissions over the study period; however, the ratio

3 McKinney et al CSCs Overcome Weekend vs Weekday Gap 2405 Figure 1. Weekend versus weekday stroke admission and mortality. of weekend to weekday admissions remained unchanged (Figure 1). Hospital Characteristics Eighty-eight hospitals were represented in this analysis; 12 were CSC, 43 were PSC, and 33 were NSC. Of the total population, 23.4% (31 417) were admitted to a CSC, 51.5% (69 275) to a PSC, and 25.1% (33 746) to a NSC. Patients with stroke were significantly more likely to be admitted to a CSC on weekends (Table 1). Patients with stroke were more likely to be admitted to the hospital through the emergency department on the weekend than weekday (89.4% versus 84.4%, P ). There was a corresponding significant decline in admissions via physician referral on weekends versus weekdays (5.3% versus 9.9%, P ). Mortality The overall 90-day mortality for patients admitted with cerebral infarction during the study was 16.7% (Table 2). Mortality 90 days after admission was significantly higher for patients admitted on weekends than on weekdays (17.2% versus 16.5%; P 0.001). In-hospital and 30-day mortality rates were also increased for patients admitted on weekends; however, this difference was diluted 1 year after admission (Table 2). Ninety-day stroke mortality declined throughout the study period for both weekend and weekday admissions (Figure 1). After adjusting for available confounding variables, 90-day mortality remained significantly higher for patients admitted on weekends than on weekdays (hazard ratio [HR], 1.05; 95% CI, 1.02 to 1.09; Table 3). Mortality was higher for patients admitted on weekends than weekdays for all time periods (Figure 1). However, the adjusted risk of death at 90 days was significantly lower for patients admitted between 2006 and 2007, the time period when New Jersey Table 2. All-Cause Mortality After Stroke Admission Total Weekend Weekday (N ) (N ) (N ) P* In-hospital (8.6%) 3357 (9.0%) 8241 (8.5%) d (11.7%) 4572 (12.3%) (11.4%) d (16.7%) 6415 (17.2%) (16.5%) y (24.1%) 9440 (25.3%) (24.9%) 0.09 *P values are based on 2 tests. began designating stroke centers, compared with 1996 and 1997 (HR, 0.86; 95% CI, 0.82 to 0.91). Additionally, we examined potential effects that PSC designation by The Joint Commission may have had by analyzing mortality before and after 2003, when The Joint Commission stroke center accreditation began. Adjusted 90-day mortality remained higher for patients admitted on weekends between 1996 and 2002 (HR, 1.05; 95% CI, 1.01 to 1.09) and 2003 and 2007 (HR, 1.05; 95% CI, 1.00 to 1.11). Table 3. Adjusted Risk of Death 90 Days After Stroke Admission Effect Hazard Ratio (95% CI) Weekend vs weekday admission 1.05 ( ) Age, y 1.05 ( ) Gender: female 1.02 ( ) Race Black vs white 0.91 ( ) Other vs white 0.84 ( ) Comorbid conditions Hypertension 0.64 ( ) Diabetes 1.02 ( ) Atrial fibrillation 1.83 ( ) Renal disease 2.35 ( ) Year of admission vs ( ) vs ( ) vs ( ) vs ( ) vs ( ) Admission source: emergency department vs other 0.93 ( ) IV tpa 1.45 ( ) Certified stroke center vs NSC 0.95 ( ) Hospital stroke case volume Second vs first quartile 1.06 ( ) Third vs first quartile 1.04 ( ) Fourth vs first quartile 1.08 ( ) IV indicates intravenous; tpa, tissue-type plasminogen activator; NSC, nonstroke centers; CI, confidence interval.

4 2406 Stroke September 2011 Table 4. Adjusted Odds of Receiving Intravenous Thrombolysis During Stroke Admission Effect OR (95% CI) Weekend admission 1.19 ( ) Year of admission vs * 3.16 ( ) vs * 3.95 ( ) vs * 5.80 ( ) vs * 9.86 ( ) Age, y 0.98 ( ) Gender: female 0.82 ( ) Race Black vs white 0.85 ( ) Other vs white 1.11 ( ) Comorbid conditions Hypertension 0.99 ( ) Diabetes 0.64 ( ) Atrial fibrillation 1.98 ( ) Renal disease 0.74 ( ) Stroke center CSC vs NSC 5.82 ( ) PSC vs NSC 2.48 ( ) CSC vs PSC 2.35 ( ) Admission source: emergency department vs other 1.48 ( ) *The comparator time period was in this analysis. International Classification of Diseases, 9th Revision code for injection or infusion of intravenous thrombolytic agent was created in CSC indicates comprehensive stroke centers; NSC, nonstroke centers; PSC, primary stroke centers; OR, odds ratio; CI, confidence interval. IV Thrombolysis IV thrombolysis rates were higher for patients with stroke admitted on weekends than weekdays (1.6% versus 1.3%; P ). The adjusted odds of treatment with IV tissuetype plasminogen activator (tpa) remained significantly higher for patients admitted on weekends (OR, 1.19; 95% CI, 1.07 to 1.31; Table 4). The adjusted odds of receiving IV tpa was also increased at CSCs (OR, 5.82; 95% CI, 4.88 to 6.94) or PSCs (OR, 2.48; 95% CI, 2.07 to 2.96) compared with NSCs. Patients with atrial fibrillation and those admitted through emergency departments were more likely to receive IV tpa; whereas women, blacks, and those with diabetes or renal disease were less likely to be treated (Table 4). By the time of initial The Joint Commission (2002 to 2003) and NJ DHSS (2006 to 2007) stroke center designation, patients were approximately 4 and 10 times more likely to receive IV tpa, respectively, than between 1998 and Stroke Center Designation Overall, patients with stroke were more likely to be admitted to CSCs than NSCs on weekends than weekdays (P 0.001). However, weekday versus weekend admissions remained similar in all time periods studied for all hospital types, except from 2006 to 2007, when there was a significant increase in the percentage of patients admitted to a CSC on weekends versus weekdays (30.3% versus 26.8%; P ). No increase in adjusted 90-day mortality was observed in patients admitted to CSC on weekends (HR, 1.01; 95% CI, 0.95 to 1.08). However, adjusted 90-day mortality was significantly greater with weekend admission to PSCs (HR, 1.06; 95% CI, 1.02 to 1.10) and NSCs (HR, 1.08; 95% CI, 1.02 to 1.15). The odds of in-hospital death by stroke center designation were similar: CSC (OR, 1.00; 95% CI, 0.92 to 1.09), PSC (OR, 1.07; 95% CI, 1.00 to 1.13), and NSC (OR, 1.10; 95% CI, 1.01 to 1.20). Trends in stroke center admission rates, IV thrombolysis, and 90-day mortality are presented in Figure 2. IV thrombolysis rates by stroke center designation are presented in Supplemental Table I ( Discussion There may be disparities in hospital care on weekends when hospital staffing is reduced. Weekend admission for myocardial infarction is associated with a higher mortality and lower use of invasive cardiac procedures. 1 This disparity has been termed the weekend effect. Previous reports examining the weekend effect in stroke care have reported variable results with most studies focusing on in-hospital mortality. 2 5,7 9 Our analysis of the MIDAS database shows that patients with stroke admitted on weekends have an increased adjusted risk of death at 90 days compared with those admitted on weekdays. Multiple studies outside of the United States have reported increased early mortality for patients with stroke admitted on weekends. The Canadian Stroke Network found an increase in 7-day mortality for patients with stroke admitted on weekends (HR, 1.12; 95% CI, 1.00 to 1.25). 9 A Taiwanese study also reported increased mortality for patients with stroke admitted on weekends. 14 However, a German study found no weekend effect on early stroke mortality. 15 Stroke care organization and delivery may be different in the United States than abroad. An analysis of the Get With The Guidelines Stroke Program found a small but significant increase in in-hospital mortality for off-hours admission (5.8% versus 5.2%; P 0.001). 4 This report may underestimate the overall weekend effect in stroke care because most hospitals participating in the Get With The Guidelines Stroke Program are CSCs. A study of stroke care in the United States using the Nationwide Inpatient Sample Database found no difference in in-hospital mortality between weekend and weekday admission between 2002 and 2007 (OR, 1.00; 95% CI, to 1.029). 8 Contrary to this report, our study did show a significant increase in in-hospital, 30-day, and 90-day mortality for patients with stroke admitted on weekends overall and between 2003 and Differences in study design may account for the differences in observations made by Hoh et al and those in our study. The former study included all admissions for an ischemic stroke diagnosis, whereas we limited ours to the first hospitalization with a primary diagnosis of ischemic stroke. Furthermore, we were able to include holiday admissions in the weekend cohort, whereas Hoh and colleagues could not. Patients admitted on weekends were more likely to receive treatment with IV tpa in this analysis. Although this trend

5 McKinney et al CSCs Overcome Weekend vs Weekday Gap 2407 Figure 2. A, Comprehensive stroke center admissions, mortality, and intravenous thrombolysis rates. B, Primary stroke center admissions, mortality, and intravenous thrombolysis rates. C, Nonstroke center admissions, mortality, and intravenous thrombolysis rates. tpa indicates tissue-type plasminogen activator.

6 2408 Stroke September 2011 was not found in an analysis of thrombolytic use in Europe, it is consistent with other previously published reports of stroke care in the United States. 7,8,16 Previously proposed explanations include: decreased traffic volume and work obligations that may decrease delays in hospital arrival; quicker access to diagnostic imaging and neurological evaluation outside of weekday work schedules; and more severe strokes on weekends. 7,8 An alternative explanation is that many physicians offices are closed on weekends, forcing patients to access health care through emergency medical services and emergency departments thereby reducing delays in hospital presentation. In our study, there was a 4.6% increase in stroke admission by physician referral during the week. This difference would account for 6000 patients who had potential delays in stroke diagnosis and treatment because medical care was not accessed by calling 911 and using established systems for delivering acute care. Furthermore, emergency medical services may triage patients with suspected stroke to stroke centers where they are more likely to be treated on weekends. The increase in weekend emergency department presentation and CSC admission observed in this study may account for increased rates of weekend IV tpa administration and deserves further study. In contrast to other states, New Jersey does not have a statute requiring emergency medical services to take patients with suspected stroke to designated stroke centers. Encouragingly, overall IV tpa rates increased 10-fold throughout the study period. This marked increase in acute stroke treatment is likely multifactorial, but undoubtedly ongoing community and healthcare provider education, stroke center designation by federal and state regulatory agencies, and hospital-based quality assurance and performance improvement initiatives are largely responsible. Albright et al reported no difference in 90-day mortality between weekend and weekday stroke admission to 2 CSCs and concluded that around the clock availability of stroke specialists, advanced neuroimaging, and specialized nursing care may account for this difference. 6 In our analysis of the MIDAS database, there was no increased risk of 90-day death with CSC admission on weekends. However, a weekend effect was present for patients with stroke admitted to PSCs or NSCs. We do not feel that this simply reflects hospital volume. In the multivariable model, admission to the highest volume centers was associated with an increase in risk of death, whereas CSC designation was associated with lower mortality. In New York State, patients admitted to designated stroke centers have a significant reduction in 30-day mortality compared with patients admitted to NSCs even after adjusting for hospital volume. 17 There are several limitations to the present study. The principal limitation is that unmeasured confounders may have contributed to the reported differences in mortality between patients admitted on weekends and those admitted on weekdays. It is possible that some of these unmeasured variables may explain or mask some of the observations. Furthermore, we applied current stroke center designations to hospitals during the study period. It is possible that these centers did not provide CSC-level care during the study period. However, we feel that the majority of CSCs in New Jersey functioned as comprehensive centers before the development of the state designation. Ten of the 12 centers received CSC designation within the first year of review (2007), and our results speak to the existence of superior care at CSC. Interestingly, there was a significant reduction in 90-day risk of death (HR, 0.86; 95% CI, 0.82 to 0.91) during the time period of NJ state stroke center designation that was not seen in other time periods. This could indicate that the statewide designation process had a positive effect on stroke care as a whole across New Jersey and deserves further study. An additional limitation is the retrospective nature of the study, which has potential for selection bias. The recently developed New Jersey Acute Stroke Registry will prospectively collect data on all stroke admissions and allow for future studies. Neither of these limitations should detract from the primary finding that 90-day mortality was increased with weekend stroke admission. Our data were collected between 1996 and 2007, and it is possible that current stroke care has improved further. This study has several important strengths, namely the large sample size that includes all patients admitted to a NJ acute care hospital over a 12-year period for a first-time diagnosis of an ischemic stroke, which may reduce or eliminate selection bias. The observation that weekend stroke admission independently increases the risk of 90-day death by 5% is both significant and clinically meaningful. This increase in mortality could account for several thousand deaths annually in the United States. More appropriate hospital staffing and organization of stroke care such as that provided by CSC may negate the weekend effect and save lives. Conclusions In the MIDAS database, 1996 to 2007, patients with stroke admitted on weekends had a significantly higher risk of death by 90 days. No difference in mortality was observed at CSCs. Sources of Funding This study was funded in part by the Robert Wood Johnson Foundation and the Schering-Plough Foundation. None. Disclosures References 1. Kostis WJ, Demissie K, Marcella SW, Shao YH, Wilson AC, Moreyra AE. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med. 2007;356: Saposnik G, Baibergenova A, Bayer N, Hachinski V. Weekends: a dangerous time for having a stroke? Stroke. 2007;38: Hasegawa Y, Yoneda Y, Okuda S, Hamada R, Toyota A, Gotoh J, et al. The effect of weekends and holidays on stroke outcome in acute stroke units. Cerebrovasc Dis. 2005;20: Reeves MJ, Smith E, Fonarow G, Hernandez A, Pan W, Schwamm LH. Off-hour admission and in-hospital stroke case fatality in the Get With The Guidelines Stroke program. Stroke. 2009;40: Janszky I, Ahnve S, Ljung R. Weekend versus weekday admission and stroke outcome in Sweden from 1968 to Stroke. 2007;38:e94; author reply e Albright KC, Raman R, Ernstrom K, Hallevi H, Martin-Schild S, Meyer BC, et al. Can comprehensive stroke centers erase the weekend effect? Cerebrovasc Dis. 2009;27:

7 McKinney et al CSCs Overcome Weekend vs Weekday Gap Kazley AS, Hillman DG, Johnston KC, Simpson KN. Hospital care for patients experiencing weekend vs weekday stroke: a comparison of quality and aggressiveness of care. Arch Neurol. 2010;67: Hoh BL, Chi YY, Waters MF, Mocco J, Barker FG II. Effect of weekend compared with weekday stroke admission on thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay in the nationwide inpatient sample database, 2002 to Stroke. 2010;41: Fang J, Saposnik G, Silver FL, Kapral MK. Association between weekend hospital presentation and stroke fatality. Neurology. 2010;75: Kostis JB, Wilson AC, O Dowd K, Gregory P, Chelton S, Cosgrove NM, et al. Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS study group. Myocardial Infarction Data Acquisition System. Circulation. 1994;90: Kostis JB, Wilson AC, Lacy CR, Cosgrove NM, Ranjan R, Lawrence- Nelson J. Time trends in the occurrence and outcome of acute myocardial infarction and coronary heart disease death between 1986 and 1996 (a New Jersey statewide study). Am J Cardiol. 2001;88: Kostis WJ, Deng Y, Pantazopoulos JS, Moreyra AE, Kostis JB. Trends in mortality of acute myocardial infarction after discharge from the hospital. Circ Cardiovasc Qual Outcomes. 2010;3: Campbell KM, Deck D, Krupski A. Record linkage software in the public domain: a comparison of link plus, the link king, and a basic deterministic algorithm. Health Informatics J. 2008;14: Tung YC, Chang GM, Chen YH. Associations of physician volume and weekend admissions with ischemic stroke outcome in Taiwan: a nationwide population-based study. Med Care. 2009;47: Jauss M, Oertel W, Allendoerfer J, Misselwitz B, Hamer H. Bias in request for medical care and impact on outcome during office and nonoffice hours in stroke patients. Eur J Neurol. 2009;16: Lees KR, Ford GA, Muir KW, Ahmed N, Dyker AG, Atula S, et al. Thrombolytic therapy for acute stroke in the united kingdom: experience from the Safe Implementation of Thrombolysis in Stroke (SITS) register. QJM. 2008;101: Xian Y, Holloway RG, Chan PS, Noyes K, Shah MN, Ting HH, et al. Association between stroke center hospitalization for acute ischemic stroke and mortality. JAMA. 2011;305: