Short report 285
Acute stroke: why do some patients arrive in time and others do not? Maarja Soomann, Riina Vibo and Janika Kõrv The aim of this study was to evaluate which factors are associated with early hospital arrival and help-seeking delays in acute stroke. All consecutive eligible patients were interviewed face-to-face within 72 h of admission. Factors associated with early arrival were assessed by univariate and multivariate analysis. The data of 195 patients were analysed. The patients who first called the emergency medical services rather than the family physician arrived earlier (odds ratio 15.9, 95% confidence interval 3.23–78.3, P < 0.01). Those who contacted the emergency medical services within 30 min of symptom onset were more likely to receive thrombolysis (odds ratio 6.9, 95% confidence interval 2.6–18.4, P < 0.01). The most common reasons for delaying seeking help were the hope for spontaneous recovery and perceiving the elapsed time as insignificant.
Introduction To date, intravenous thrombolysis and stroke unit care are the only approved treatment options for acute ischaemic stroke [1]. The benefits of intravenous thrombolysis outweigh the safety risks only when the treatment is provided within 4.5 h from stroke onset [2]. The major reasons for not receiving thrombolytic treatment have been shown to be prehospital delays [3]. Arrival speed depends on the actions of both the patient and the emergency medical services (EMS). Possible reasons for delays have been studied, but to date, the findings have been contradictory. The aim of this study was to investigate the factors associated with patients’ hospital arrival after stroke onset and the reasons for help-seeking delays.
Patients and methods All consecutive patients with a diagnosis of acute stroke or transient ischaemic attack (TIA) admitted to the Tartu University Hospital, Department of Neurology, were registered during 9 months in 2010. The exclusion criteria for the study were impaired consciousness, severe aphasia, early discharge, subarachnoid haemorrhage and refusal to participate. The catchment area of the study hospital covers ∼ 150 000 individuals and consists of the urban area of Tartu and its mostly rural surroundings in the range of 85 km. It is the only hospital in the region that provides intravenous thrombolytic treatment for acute stroke patients. 0969-9546 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients probably neglect symptoms because of stroke itself and therefore do not act fast enough. European Journal of Emergency Medicine 22:285–287 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Emergency Medicine 2015, 22:285–287 Keywords: acute stroke, early hospital arrival, onset-to-door times, reasons for prehospital delays, thrombolysis Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia Correspondence to Maarja Soomann, Department of Neurology and Neurosurgery, University of Tartu, Puusepa 8, Tartu 51014, Estonia Tel: + 372 7 318 514; fax: + 372 7 318 509; e-mail: [email protected] Received 12 June 2014 Accepted 11 August 2014
Face-to-face interviews with the patients were conducted within the first 72 h of admission by the same person, who asked standardized open-ended questions. The patients were interviewed about stroke symptoms, actions taken on stroke onset, reasons for help-seeking delays, living arrangements, family physician visits and family history of stroke. The patients’ medical records were used to collect additional information. Stroke was classified into brain infarction and intracerebral haemorrhage according to computed tomography findings. Stroke risk factors were registered on the basis of the patient’s medical history. Onset of stroke was defined as the moment when the patient or a proxy had first noticed the symptoms. If the patient woke up with symptoms, the time of onset was defined as the last moment when the patient was symptom free. Calling early was defined as having called the emergency number within 30 min from symptom onset. Early arrival was defined as having arrived at the hospital within 3 h of symptom onset. Student’s independent two-sample t-test was used for continuous variables and Pearson’s χ2-test for categorical variables. Factors associated with early arrival were assessed by univariate and multivariate analysis. The explanatory variables tested in univariate analysis were mean age, sex, type of stroke, having recognized stroke symptoms on site, receiver of first telephone call, concomitant diseases (hypertension, atrial fibrillation, diabetes, ischaemic heart disease, congestive heart failure), smoking, medication DOI: 10.1097/MEJ.0000000000000206
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
286 European Journal of Emergency Medicine 2015, Vol 22 No 4
(antiplatelets or oral anticoagulants), history of stroke, family history of stroke, place of residence (in Tartu or outside of Tartu), living arrangements (together with someone or alone), side of stroke and last visit to the family physician. The same variables were considered for the multivariate analysis by stepwise logistic regression. The stepwise procedure was started with an empty model and in every subsequent step one variable was added or removed to achieve improvement in the Akaike information criterion. Associations were considered statistically significant when P-value was less than 0.05. The statistical analysis was carried out using R version 2.14.1 (R Foundation for Statistical Computing, Vienna, Austria). All patients were informed of the nature and the aims of the study and provided written consent before the interviews. The study protocol was approved by the Ethics Review Committee on Human Research of the University of Tartu.
Results During the study period, 341 acute stroke/TIA patients were admitted. The data of 195 (58%) patients were included in the analysis. Eleven (3%) patients refused to participate in the study, 86 (25%) were excluded because of severe aphasia, 16 (5%) because of a final diagnosis other than stroke/TIA, 15 (4%) because of impaired consciousness, 15 (4%) because of early discharge and three (1%) because of death. The patients excluded were older than the patients in the study group (P < 0.01), but there were no statistically significant sex differences (P = 0.09). The mean age of the final study group was 71.6 (± 12.4) years; other basic characteristics are shown in Table 1. Stroke was recognized by 36 (18%) patients. The first telephone call was made to the EMS in 106 (54%) cases (Table 1). Less than a third of the patients (31%) who first contacted the EMS called early. Thirty (28%) patients reported not having delayed with calling the EMS, although objectively more than 30 min had passed since symptom onset. The most common reason [28 (26%) patients] for not calling early was the hope for spontaneous recovery. Nine (9%) patients reported that they were unable to seek help because of symptoms and six (6%) patients had other reasons for delaying. The onset-to-door time was 1 h or less in 22 (11%) patients, 1–2 h in 48 (25%) patients and 2–3 h in 16 (8%) patients. The total number of early arrivals was 86 (44%). Of the 165 patients who had suffered from a brain infarction, 23 (14%) patients received thrombolysis. The patients who had called the EMS early received thrombolysis more likely than those who had called later (odds ratio 6.9, 95% confidence interval 2.6–18.4, P < 0.01). Univariate analysis showed that the odds for early hospital arrival were influenced only by the first telephone call. The patients who first called the EMS rather than
Table 1
General characteristics of the study population (N = 195)
Variables
N (%)
Sex Men Women Type of stroke BI ICH TIA Side of stroke Left hemisphere Right hemisphere Bilateral Brainstem and/or cerebellum Risk factors Hypertension Atrial fibrillation Congestive heart failure Previous stroke or TIA Diabetes Ischaemic heart disease Smoking Last family physician visit During the month before stroke 2–6 months before stroke 7–12 months before stroke Over a year before stroke Place of residence In Tartu Outside of Tartu Living arrangements Together with someone Alone First telephone call Emergency number Family physician Relative Unknown No calls made
95 (49) 100 (51) 165 (84) 19 (10) 11 (6) 81 76 5 33
(41) (39) (3) (17)
154 74 56 40 35 21 45
(79) (38) (29) (21) (18) (11) (23)
78 58 17 42
(40) (30) (9) (21)
84 (43) 111 (57) 139 (71) 56 (29) 106 27 45 6 11
(54) (14) (23) (3) (6)
BI, brain infarction; ICH, intracerebral haemorrhage; TIA, transient ischaemic attack.
their family physician were more likely to arrive within 3 h from symptom onset (odds ratio 12.8, 95% confidence interval 3.5–83.4, P < 0.01). According to the final stepwise logistic regression model (Table 2) adjusted to place of residence and living Table 2
Factors influencing early hospital arrival Estimate
P-value
First call to family physician (base category) To the emergency number 2.77 < 0.001* To a relative 1.63 0.05 Unknown 2.80 0.02* No calls made 1.53 0.19 Recurrent stroke First-ever stroke 0.87 < 0.05* Last family physician visit during the month before stroke 2–6 months before the stroke − 1.33 0.03* 7–12 months before the stroke − 0.90 0.20 Over a year before the stroke −0.87 0.11 Unknown –0.47 0.55 Place of residence outside of Tartu In Tartu 0.64 0.09 Living alone Living together with someone 0.69 0.13 CI, confidence interval. *Statistically significant in the final model.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Odds ratio (95% CI) 15.9 5.12 16.5 4.62
(3.23–78.3) (0.97–27.1) (1.62–168.1) (0.47–45.1)
2.38 (1.01–5.63) 0.27 0.41 0.42 0.62
(0.11–0.64) (0.10–1.62) (0.14–1.22) (0.13–2.99)
1.89 (0.91–3.93) 1.98 (0.82–4.82)
Hospital arrival in acute stroke Soomann et al. 287
arrangements, significant predictors of early arrival were receiver of the first telephone call, history of a previous stroke and time since the last family physician visit.
Discussion The most important finding of our study is that onset-todoor time is strongly associated with the first contact after stroke onset: first calling the EMS instead of contacting the family physician proved to accelerate hospital arrival. This finding is consistent with several previous studies [4,5]. The patients who called the EMS early had significantly higher chances of receiving thrombolysis.
Conclusion
Our study showed that first calling the EMS on stroke onset is closely related to faster hospital arrival. The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients neglect symptoms because of stroke itself and consequently do not act fast enough. Stroke awareness campaigns should stress the need for calling the EMS immediately.
Acknowledgements The authors thank Anne Selart for assistance with the statistical analysis.
The association between early arrival and having visited the family physician during the month before stroke might be related to patients’ overall health behaviour: those who pay more attention to their health might also be able to react more adequately in case of an emergency.
The study was supported by the Estonian IUT2-4 grant.
The percentage of early arrivals in our study is among the highest reported in Western countries [6]. We believe that this is because of the well-organized and free of charge EMS in Estonia.
References
Similar to earlier studies [7,8], one of the most common reasons for delaying seeking help was the hope for spontaneous recovery. A quarter of the patients reported not having delayed significantly, although over 30 min had elapsed since symptom onset. Many probably neglect their symptoms because of stroke itself and therefore do not act fast enough. The strength of our study is that in addition to using standard health data, acute stroke patients were interviewed face-to-face within 72 h from hospitalization, which enabled us to collect as accurate data as possible. The limitations of our study are a small sample size and a possible bias because of the exclusion of many patients with severe stroke.
Conflicts of interest
There are no conflicts of interest.
1 2
3
4
5
6
7
8
Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2007; 4:CD000197. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375:1695–1703. Van den Berg JS, de Jong G. Why ischemic stroke patients do not receive thrombolytic treatment: results from a general hospital. Acta Neurol Scand 2009; 120:157–160. Geffner D, Soriano C, Pérez T, Vilar C, Rodríguez D. Delay in seeking treatment by patients with stroke: who decides, where they go, and how long it takes. Clin Neurol Neurosurg 2012; 114:21–25. Mandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke 2006; 37:1248–1253. Evenson KR, Foraker RE, Morris DL, Rosamond WD. A comprehensive review of pre-hospital and in-hospital delay times in acute stroke care. Int J Stroke 2009; 4:187–199. Abilleira S, Lucente G, Ribera A, Permanyer-Miralda G, Gallofré M. Patientrelated features associated with a delay in seeking care after stroke. Eur J Neurol 2011; 18:850–856. Hsia AW, Castle A, Wing JJ, Edwards DF, Brown NC, Higgins TM, et al. Understanding reasons for delay in seeking acute stroke care in an underserved urban population. Stroke 2011; 42:1697–1701.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Acute stroke: why do some patients arrive in time and others do not? Maarja Soomann, Riina Vibo and Janika Kõrv The aim of this study was to evaluate which factors are associated with early hospital arrival and help-seeking delays in acute stroke. All consecutive eligible patients were interviewed face-to-face within 72 h of admission. Factors associated with early arrival were assessed by univariate and multivariate analysis. The data of 195 patients were analysed. The patients who first called the emergency medical services rather than the family physician arrived earlier (odds ratio 15.9, 95% confidence interval 3.23–78.3, P < 0.01). Those who contacted the emergency medical services within 30 min of symptom onset were more likely to receive thrombolysis (odds ratio 6.9, 95% confidence interval 2.6–18.4, P < 0.01). The most common reasons for delaying seeking help were the hope for spontaneous recovery and perceiving the elapsed time as insignificant.
Introduction To date, intravenous thrombolysis and stroke unit care are the only approved treatment options for acute ischaemic stroke [1]. The benefits of intravenous thrombolysis outweigh the safety risks only when the treatment is provided within 4.5 h from stroke onset [2]. The major reasons for not receiving thrombolytic treatment have been shown to be prehospital delays [3]. Arrival speed depends on the actions of both the patient and the emergency medical services (EMS). Possible reasons for delays have been studied, but to date, the findings have been contradictory. The aim of this study was to investigate the factors associated with patients’ hospital arrival after stroke onset and the reasons for help-seeking delays.
Patients and methods All consecutive patients with a diagnosis of acute stroke or transient ischaemic attack (TIA) admitted to the Tartu University Hospital, Department of Neurology, were registered during 9 months in 2010. The exclusion criteria for the study were impaired consciousness, severe aphasia, early discharge, subarachnoid haemorrhage and refusal to participate. The catchment area of the study hospital covers ∼ 150 000 individuals and consists of the urban area of Tartu and its mostly rural surroundings in the range of 85 km. It is the only hospital in the region that provides intravenous thrombolytic treatment for acute stroke patients. 0969-9546 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients probably neglect symptoms because of stroke itself and therefore do not act fast enough. European Journal of Emergency Medicine 22:285–287 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Emergency Medicine 2015, 22:285–287 Keywords: acute stroke, early hospital arrival, onset-to-door times, reasons for prehospital delays, thrombolysis Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia Correspondence to Maarja Soomann, Department of Neurology and Neurosurgery, University of Tartu, Puusepa 8, Tartu 51014, Estonia Tel: + 372 7 318 514; fax: + 372 7 318 509; e-mail: [email protected] Received 12 June 2014 Accepted 11 August 2014
Face-to-face interviews with the patients were conducted within the first 72 h of admission by the same person, who asked standardized open-ended questions. The patients were interviewed about stroke symptoms, actions taken on stroke onset, reasons for help-seeking delays, living arrangements, family physician visits and family history of stroke. The patients’ medical records were used to collect additional information. Stroke was classified into brain infarction and intracerebral haemorrhage according to computed tomography findings. Stroke risk factors were registered on the basis of the patient’s medical history. Onset of stroke was defined as the moment when the patient or a proxy had first noticed the symptoms. If the patient woke up with symptoms, the time of onset was defined as the last moment when the patient was symptom free. Calling early was defined as having called the emergency number within 30 min from symptom onset. Early arrival was defined as having arrived at the hospital within 3 h of symptom onset. Student’s independent two-sample t-test was used for continuous variables and Pearson’s χ2-test for categorical variables. Factors associated with early arrival were assessed by univariate and multivariate analysis. The explanatory variables tested in univariate analysis were mean age, sex, type of stroke, having recognized stroke symptoms on site, receiver of first telephone call, concomitant diseases (hypertension, atrial fibrillation, diabetes, ischaemic heart disease, congestive heart failure), smoking, medication DOI: 10.1097/MEJ.0000000000000206
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
286 European Journal of Emergency Medicine 2015, Vol 22 No 4
(antiplatelets or oral anticoagulants), history of stroke, family history of stroke, place of residence (in Tartu or outside of Tartu), living arrangements (together with someone or alone), side of stroke and last visit to the family physician. The same variables were considered for the multivariate analysis by stepwise logistic regression. The stepwise procedure was started with an empty model and in every subsequent step one variable was added or removed to achieve improvement in the Akaike information criterion. Associations were considered statistically significant when P-value was less than 0.05. The statistical analysis was carried out using R version 2.14.1 (R Foundation for Statistical Computing, Vienna, Austria). All patients were informed of the nature and the aims of the study and provided written consent before the interviews. The study protocol was approved by the Ethics Review Committee on Human Research of the University of Tartu.
Results During the study period, 341 acute stroke/TIA patients were admitted. The data of 195 (58%) patients were included in the analysis. Eleven (3%) patients refused to participate in the study, 86 (25%) were excluded because of severe aphasia, 16 (5%) because of a final diagnosis other than stroke/TIA, 15 (4%) because of impaired consciousness, 15 (4%) because of early discharge and three (1%) because of death. The patients excluded were older than the patients in the study group (P < 0.01), but there were no statistically significant sex differences (P = 0.09). The mean age of the final study group was 71.6 (± 12.4) years; other basic characteristics are shown in Table 1. Stroke was recognized by 36 (18%) patients. The first telephone call was made to the EMS in 106 (54%) cases (Table 1). Less than a third of the patients (31%) who first contacted the EMS called early. Thirty (28%) patients reported not having delayed with calling the EMS, although objectively more than 30 min had passed since symptom onset. The most common reason [28 (26%) patients] for not calling early was the hope for spontaneous recovery. Nine (9%) patients reported that they were unable to seek help because of symptoms and six (6%) patients had other reasons for delaying. The onset-to-door time was 1 h or less in 22 (11%) patients, 1–2 h in 48 (25%) patients and 2–3 h in 16 (8%) patients. The total number of early arrivals was 86 (44%). Of the 165 patients who had suffered from a brain infarction, 23 (14%) patients received thrombolysis. The patients who had called the EMS early received thrombolysis more likely than those who had called later (odds ratio 6.9, 95% confidence interval 2.6–18.4, P < 0.01). Univariate analysis showed that the odds for early hospital arrival were influenced only by the first telephone call. The patients who first called the EMS rather than
Table 1
General characteristics of the study population (N = 195)
Variables
N (%)
Sex Men Women Type of stroke BI ICH TIA Side of stroke Left hemisphere Right hemisphere Bilateral Brainstem and/or cerebellum Risk factors Hypertension Atrial fibrillation Congestive heart failure Previous stroke or TIA Diabetes Ischaemic heart disease Smoking Last family physician visit During the month before stroke 2–6 months before stroke 7–12 months before stroke Over a year before stroke Place of residence In Tartu Outside of Tartu Living arrangements Together with someone Alone First telephone call Emergency number Family physician Relative Unknown No calls made
95 (49) 100 (51) 165 (84) 19 (10) 11 (6) 81 76 5 33
(41) (39) (3) (17)
154 74 56 40 35 21 45
(79) (38) (29) (21) (18) (11) (23)
78 58 17 42
(40) (30) (9) (21)
84 (43) 111 (57) 139 (71) 56 (29) 106 27 45 6 11
(54) (14) (23) (3) (6)
BI, brain infarction; ICH, intracerebral haemorrhage; TIA, transient ischaemic attack.
their family physician were more likely to arrive within 3 h from symptom onset (odds ratio 12.8, 95% confidence interval 3.5–83.4, P < 0.01). According to the final stepwise logistic regression model (Table 2) adjusted to place of residence and living Table 2
Factors influencing early hospital arrival Estimate
P-value
First call to family physician (base category) To the emergency number 2.77 < 0.001* To a relative 1.63 0.05 Unknown 2.80 0.02* No calls made 1.53 0.19 Recurrent stroke First-ever stroke 0.87 < 0.05* Last family physician visit during the month before stroke 2–6 months before the stroke − 1.33 0.03* 7–12 months before the stroke − 0.90 0.20 Over a year before the stroke −0.87 0.11 Unknown –0.47 0.55 Place of residence outside of Tartu In Tartu 0.64 0.09 Living alone Living together with someone 0.69 0.13 CI, confidence interval. *Statistically significant in the final model.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Odds ratio (95% CI) 15.9 5.12 16.5 4.62
(3.23–78.3) (0.97–27.1) (1.62–168.1) (0.47–45.1)
2.38 (1.01–5.63) 0.27 0.41 0.42 0.62
(0.11–0.64) (0.10–1.62) (0.14–1.22) (0.13–2.99)
1.89 (0.91–3.93) 1.98 (0.82–4.82)
Hospital arrival in acute stroke Soomann et al. 287
arrangements, significant predictors of early arrival were receiver of the first telephone call, history of a previous stroke and time since the last family physician visit.
Discussion The most important finding of our study is that onset-todoor time is strongly associated with the first contact after stroke onset: first calling the EMS instead of contacting the family physician proved to accelerate hospital arrival. This finding is consistent with several previous studies [4,5]. The patients who called the EMS early had significantly higher chances of receiving thrombolysis.
Conclusion
Our study showed that first calling the EMS on stroke onset is closely related to faster hospital arrival. The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients neglect symptoms because of stroke itself and consequently do not act fast enough. Stroke awareness campaigns should stress the need for calling the EMS immediately.
Acknowledgements The authors thank Anne Selart for assistance with the statistical analysis.
The association between early arrival and having visited the family physician during the month before stroke might be related to patients’ overall health behaviour: those who pay more attention to their health might also be able to react more adequately in case of an emergency.
The study was supported by the Estonian IUT2-4 grant.
The percentage of early arrivals in our study is among the highest reported in Western countries [6]. We believe that this is because of the well-organized and free of charge EMS in Estonia.
References
Similar to earlier studies [7,8], one of the most common reasons for delaying seeking help was the hope for spontaneous recovery. A quarter of the patients reported not having delayed significantly, although over 30 min had elapsed since symptom onset. Many probably neglect their symptoms because of stroke itself and therefore do not act fast enough. The strength of our study is that in addition to using standard health data, acute stroke patients were interviewed face-to-face within 72 h from hospitalization, which enabled us to collect as accurate data as possible. The limitations of our study are a small sample size and a possible bias because of the exclusion of many patients with severe stroke.
Conflicts of interest
There are no conflicts of interest.
1 2
3
4
5
6
7
8
Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2007; 4:CD000197. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375:1695–1703. Van den Berg JS, de Jong G. Why ischemic stroke patients do not receive thrombolytic treatment: results from a general hospital. Acta Neurol Scand 2009; 120:157–160. Geffner D, Soriano C, Pérez T, Vilar C, Rodríguez D. Delay in seeking treatment by patients with stroke: who decides, where they go, and how long it takes. Clin Neurol Neurosurg 2012; 114:21–25. Mandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke 2006; 37:1248–1253. Evenson KR, Foraker RE, Morris DL, Rosamond WD. A comprehensive review of pre-hospital and in-hospital delay times in acute stroke care. Int J Stroke 2009; 4:187–199. Abilleira S, Lucente G, Ribera A, Permanyer-Miralda G, Gallofré M. Patientrelated features associated with a delay in seeking care after stroke. Eur J Neurol 2011; 18:850–856. Hsia AW, Castle A, Wing JJ, Edwards DF, Brown NC, Higgins TM, et al. Understanding reasons for delay in seeking acute stroke care in an underserved urban population. Stroke 2011; 42:1697–1701.
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
