FULL-LENGTH ORIGINAL RESEARCH
In-hospital costs in patients with seizures and epilepsy after stroke *†‡Alla Guekht, †‡Maria Mizinova, †‡Andrey Ershov, †‡Denis Guz, †‡Igor Kaimovsky, §Paolo Messina, and §Ettore Beghi Epilepsia, 56(8):1309–1313, 2015 doi: 10.1111/epi.13062
SUMMARY
Professor Alla Guekht is director of Moscow Research and Clinical Center for Neuropsychiatry.
Objectives: To verify the net effect of seizures after stroke on the use of in-hospital health care resources. Methods: Consecutive patients with first-ever stroke were admitted to the stroke unit of a Moscow hospital and followed prospectively until death or discharge. Each patient experiencing seizures was matched for age, sex, stroke type, National Institutes of Health Stroke Scale score at admission, and stroke risk factors to 2+ patients with no seizures, as controls. Resources consumed included length of hospital stay, admission to the intensive care unit (ICU), diagnostic tests, medical consultations and treatments. Cost estimates were based on the Russian National Health Service perspective. Results: The sample comprised 30 patients with in-hospital seizures and 70 matched controls. Patients dying in hospital were 15 of 30 (50%) versus 4 of 70 (5.7%) (p < 0.001). The overall cost of hospital stay was only slightly (nonsignificantly) higher in patients with seizures, but the cost was significantly higher in patients who died than in patients who were discharged alive. Compared to the controls, patients with seizures spent more intensive care unit (ICU) days and required more computed tomography (CT) scans, x-rays, endoscopies, and specialist consultations, causing higher inhospital costs. Significance: In patients with first-ever stroke, seizures per se do not increase the overall in-hospital costs. However, the higher than expected mortality in patients with seizures is associated with additional hospital costs. KEY WORDS: Seizures, Epilepsy, Stroke, Direct costs, Treatment, Russia.
Seizures and epilepsy are a common complication of stroke. Early (acute symptomatic) seizures tend to occur in up to 6% of cases1–3 and late (unprovoked) seizures in 2– 4%,4 carrying increased morbidity and mortality after stroke.5 In Russia, cerebrovascular disease was identified as Accepted May 15, 2015; Early View publication June 13, 2015. *Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russian Federation; †Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow, Russian Federation; ‡Moscow City Hospital No. 12, Moscow, Russian Federation; and §IRCCS “Mario Negri” Institute for Pharmacological Research, Milan, Italy Address correspondence to Ettore Beghi, Laboratory of Neurological Disorders, IRCCS-Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, 20156 Milan, Italy. E-mail: ettore.beghi@ marionegri.it Wiley Periodicals, Inc. © 2015 International League Against Epilepsy
the etiology of epilepsy in 12.3% of cases with localizationrelated epilepsies, with the highest proportion (15%) in the western areas of the country, including Moscow.6 Risk factors for seizures and epilepsy include stroke severity, cortical lesions, and type and degree of functional disability.3,7,8 These factors, along with comorbidities in patients presenting seizures after stroke, may partly explain at least the more ominous prognosis, and consequently the burden of the disease and its costs, in patients with poststroke seizures and epilepsy compared to individuals who do not develop seizures. A disabling stroke is associated with higher direct costs.9 Epilepsy itself is a substantial socioeconomic burden at different levels in Europe.10 However, in published reports, the net effect of epilepsy and seizures on the outcome of the disease and resource consumption has not been disentangled
1309
1310 A. Guekht et al.
Key Points • • • • •
The objective of the study was to verify the net effect of seizures after stroke on the use of in-hospital health care resources. 30 patients with first-ever stroke, admitted to the stroke unit of a Moscow hospital, were followed prospectively until death or discharge. Patients were matched for age, sex, stroke type, NIHSS score at admission, and stroke risk factors to 2+ controls with no seizures. Compared to the controls, patients with seizures spent more ICU days, required more tests and specialist consultations, and had more deaths at discharge. Seizures, with higher than expected mortality, are an independent source of additional hospital costs in patients with first stroke.
from the underlying clinical conditions. We therefore carried out an observational study to investigate the independent prognostic role of seizures and epilepsy in patients with stroke and their effects on the consumption of medical resources. Our hypothesis was that having seizures and/or epilepsy involve per se greater use of hospital resources and is consequently a source of additional direct costs in a cohort of patients with stroke after event.
Materials and Methods This was a prospective single-center cohort study. Consecutive patients with first-ever stroke were included, characterized by cerebral infarction and/or intracerebral hemorrhage and admitted to the stroke unit of the Moscow City Hospital no. 12 from October 2010 to September 2012. Patients with transient ischemic attacks, subarachnoid hemorrhage, cerebral vein thrombosis, and brainstem stroke were excluded. Also excluded were patients with a history of seizures before stroke. As specified by the World Health Organization, stroke was defined as a focal (or global) neurologic impairment of sudden onset lasting more than 24 h (or leading to death), of presumed vascular origin.11 Stroke subtypes (ischemic and hemorrhagic) were further classified on the basis of computed tomography. The side of the stroke was recorded and the severity was classified according to the National Institutes of Health Stroke Scale (NIHSS).12 Epileptic seizures were defined according to the International League Against Epilepsy (ILAE).13 Seizure detection was the task of the physicians and nurses who were present during each patient’s hospital stay. Seizures were coded as early (within 7 days of the stroke) or late (occurring after 7 days). Documented stroke risk factors and relevant comorbidities were Epilepsia, 56(8):1309–1313, 2015 doi: 10.1111/epi.13062
also identified. These included arterial hypertension, diabetes, ischemic heart disease, atrial fibrillation, and pulmonary and renal diseases. Hypertension was defined as blood pressure >140/90 mm Hg at least twice while in hospital after day 1. Diabetes mellitus was defined as preprandial blood glucose >126 mg/dl on two examinations, postprandial glucose >200 mg/dl, or hemoglobin A1c (HbA1c) >8.5%. History of ischemic heart disease, atrial fibrillation, pulmonary disease, and renal disease was obtained from patients’ past and present records and from ad hoc treatments. We did not do any power calculations because no specific differences were expected between patients with and without seizures. Enrollment was stopped when a convenience sample of 30 patients with early or late seizures was identified during follow-up. Because our research hypothesis was to calculate the extra costs (if any) attributable to epileptic seizures, we controlled for other sources of cost such as disease type, severity, and risk factors. For each patient with seizures, two or more controls were identified among those without seizures and matched for age (5 years), sex, stroke type, NIHSS score at admission, and stroke risk factors. Cases and controls were followed until discharge or death (whichever came first). For each case and matched controls a number of variables were collected from the medical records. These included the main demographic findings (age and sex), the clinical features at hospital admission (stroke type and site, the NIHSS score at admission, and all relevant comorbidities), and the items indicating the health care resources consumed for the management of stroke and its complications during the acute phase and in-hospital follow-up. These include the length of hospital stay, the stay in the intensive care unit (ICU), diagnostic tests and any other test for the assessment of stroke complications and comorbidities, medical consultations, and therapeutic measures. Cost estimates were based on the Russian National Health Service perspective and its implementation in the City of Moscow, which is based on mandatory health care insurance with reimbursement to the health care providers for services and treatments for the management of all diseases. The amount of reimbursement is specific for each diagnosis and constitutes the “medical-economic standard.” These costs (“standard costs”) are calculated as the costs of hospital stay (daily cost multiplied by the number of days); drugs were included in these costs.14,15 In the real clinical situation, management was tailored to the needs of each individual patient and all the necessary additional investigations, consultations, and interventions were done. These additional costs (exceeding the standard) were calculated and evaluated separately. Unit costs of specialist consultations and laboratory and instrumental tests were estimated by applying the tariffs approved for Moscow. The total cost consisted of the costs according to the “medical-economic standard” and the additional costs.
1311 Epilepsy and Hospital Costs of Stroke Descriptive statistics were computed on each demographic features, diagnostic, and therapeutic procedure separately. Differences between cases and controls were assessed using the chi-square test and the Student’s t-test, where indicated. Total costs in patients with and without seizures were compared by univariate analyses. Post hoc analysis was also done using a generalized linear model to test the total costs in the two groups after adjusting for vital status (dead or alive), an important source of expenditures. Data were analyzed using the SAS package for PC (9.2 version; SAS Institute, Inc., Cary, NC, U.S.A.).
Results During the study, 325 consecutive patients were admitted to the Moscow hospital. On September 30, 2012, 30 patients presented seizures while in hospital. Seizures occurred on day 1 in 21 cases, on days 2–3 in five cases, days 4–6 in one case, and days 21–28 in three cases. Accordingly, 27 patients had early seizures and three late seizures. There were no cases with status epilepticus. Among patients who had no seizures on that date, 70 fulfilled the matching criteria for controls. Cases and controls were followed for median periods of, respectively, 23 days (range 2–56) and 22 days (range 8–72). The demographic and clinical characteristics of cases and controls are illustrated in Table 1. The age at stroke diagnosis ranged from 35 to 85 years in both groups. There was a slight predominance of males in both groups. Ischemic stroke in the left carotid area was predominant in cases and controls. Arterial hypertension, ischemic heart disease,
Table 1. Demographic characteristics of patients in case and control groups Patients with stroke and seizures (30) Demographics Age, years (mean SD) Male (%) Stroke type (%) Left ischemic Right ischemic Hemorrhagic Comorbidities and stroke risk factors (%) Diabetes Hypertension Ischemic heart disease Atrial fibrillation Pulmonary disease Renal disease NIHSS (mean SD)
Patients with stroke without seizure (70)
p-Value
65.9 10.6
67.8 10.9
0.38
16 (53.3)
36 (51.4)
0.92
14 (46.7) 11 (36.7) 5 (16.7)
35 (50) 25 (35.7) 10 (14.3)
0.86 0.95 0.79
atrial fibrillation, pulmonary disease, and diabetes were, in decreasing order, the most common comorbidities in both groups (Table 1). Seizures were all focal with or without secondary generalization. Fifty percent of cases (15/30) died in hospital, compared to 5.7% of controls (4/70) (p < 0.001). Among survivors, NIHSS score at discharge was 3.3 (standard deviation) 1.8 in cases versus 3.8 2.9 in controls, a nonsignificant difference. The overall hospital stay was similar in patients with and without seizures (Table 2). However, patients with seizures spent more days in the ICU and fewer days in the neurology ward. Compared to controls, patients with seizures required more computed tomography scans, x-rays and endoscopies, and specialist consultations. The overall cost of hospital stay was slightly (nonsignificantly) higher in patients with seizures and was mostly accounted for by the ICU costs (Table 3). The cost of additional (above the standard) consultations and, except for ultrasound, the cost of diagnostic tests were significantly higher among cases than controls (Table 4). The total cost was significantly higher in patients who died than in patients who were discharged alive (US$ 4173.95 vs. 1584.98 US$; p < 0.0001). After adjusting for vital status, patients with and without seizures had fairly similar cost estimates (Table S1). Table 2. Resource consumption by cases and controls Stroke with seizures (30) (mean SD) Hospital stay, days Days in neurology ward Days in ICU CT, no. Consultations (for one person, no.) X-ray studies, no. Blood and urine tests, no. Blood biochemistry tests, no. Endoscopies, no.
22.1 14.9 7.3 2.6 4.9
11.9 10.9 8.9 1.8 1.8
Stroke without seizures (70) (mean SD)
p-Value
0.34 0.03 0.03
In-hospital costs in patients with seizures and epilepsy after stroke *†‡Alla Guekht, †‡Maria Mizinova, †‡Andrey Ershov, †‡Denis Guz, †‡Igor Kaimovsky, §Paolo Messina, and §Ettore Beghi Epilepsia, 56(8):1309–1313, 2015 doi: 10.1111/epi.13062
SUMMARY
Professor Alla Guekht is director of Moscow Research and Clinical Center for Neuropsychiatry.
Objectives: To verify the net effect of seizures after stroke on the use of in-hospital health care resources. Methods: Consecutive patients with first-ever stroke were admitted to the stroke unit of a Moscow hospital and followed prospectively until death or discharge. Each patient experiencing seizures was matched for age, sex, stroke type, National Institutes of Health Stroke Scale score at admission, and stroke risk factors to 2+ patients with no seizures, as controls. Resources consumed included length of hospital stay, admission to the intensive care unit (ICU), diagnostic tests, medical consultations and treatments. Cost estimates were based on the Russian National Health Service perspective. Results: The sample comprised 30 patients with in-hospital seizures and 70 matched controls. Patients dying in hospital were 15 of 30 (50%) versus 4 of 70 (5.7%) (p < 0.001). The overall cost of hospital stay was only slightly (nonsignificantly) higher in patients with seizures, but the cost was significantly higher in patients who died than in patients who were discharged alive. Compared to the controls, patients with seizures spent more intensive care unit (ICU) days and required more computed tomography (CT) scans, x-rays, endoscopies, and specialist consultations, causing higher inhospital costs. Significance: In patients with first-ever stroke, seizures per se do not increase the overall in-hospital costs. However, the higher than expected mortality in patients with seizures is associated with additional hospital costs. KEY WORDS: Seizures, Epilepsy, Stroke, Direct costs, Treatment, Russia.
Seizures and epilepsy are a common complication of stroke. Early (acute symptomatic) seizures tend to occur in up to 6% of cases1–3 and late (unprovoked) seizures in 2– 4%,4 carrying increased morbidity and mortality after stroke.5 In Russia, cerebrovascular disease was identified as Accepted May 15, 2015; Early View publication June 13, 2015. *Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russian Federation; †Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow, Russian Federation; ‡Moscow City Hospital No. 12, Moscow, Russian Federation; and §IRCCS “Mario Negri” Institute for Pharmacological Research, Milan, Italy Address correspondence to Ettore Beghi, Laboratory of Neurological Disorders, IRCCS-Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, 20156 Milan, Italy. E-mail: ettore.beghi@ marionegri.it Wiley Periodicals, Inc. © 2015 International League Against Epilepsy
the etiology of epilepsy in 12.3% of cases with localizationrelated epilepsies, with the highest proportion (15%) in the western areas of the country, including Moscow.6 Risk factors for seizures and epilepsy include stroke severity, cortical lesions, and type and degree of functional disability.3,7,8 These factors, along with comorbidities in patients presenting seizures after stroke, may partly explain at least the more ominous prognosis, and consequently the burden of the disease and its costs, in patients with poststroke seizures and epilepsy compared to individuals who do not develop seizures. A disabling stroke is associated with higher direct costs.9 Epilepsy itself is a substantial socioeconomic burden at different levels in Europe.10 However, in published reports, the net effect of epilepsy and seizures on the outcome of the disease and resource consumption has not been disentangled
1309
1310 A. Guekht et al.
Key Points • • • • •
The objective of the study was to verify the net effect of seizures after stroke on the use of in-hospital health care resources. 30 patients with first-ever stroke, admitted to the stroke unit of a Moscow hospital, were followed prospectively until death or discharge. Patients were matched for age, sex, stroke type, NIHSS score at admission, and stroke risk factors to 2+ controls with no seizures. Compared to the controls, patients with seizures spent more ICU days, required more tests and specialist consultations, and had more deaths at discharge. Seizures, with higher than expected mortality, are an independent source of additional hospital costs in patients with first stroke.
from the underlying clinical conditions. We therefore carried out an observational study to investigate the independent prognostic role of seizures and epilepsy in patients with stroke and their effects on the consumption of medical resources. Our hypothesis was that having seizures and/or epilepsy involve per se greater use of hospital resources and is consequently a source of additional direct costs in a cohort of patients with stroke after event.
Materials and Methods This was a prospective single-center cohort study. Consecutive patients with first-ever stroke were included, characterized by cerebral infarction and/or intracerebral hemorrhage and admitted to the stroke unit of the Moscow City Hospital no. 12 from October 2010 to September 2012. Patients with transient ischemic attacks, subarachnoid hemorrhage, cerebral vein thrombosis, and brainstem stroke were excluded. Also excluded were patients with a history of seizures before stroke. As specified by the World Health Organization, stroke was defined as a focal (or global) neurologic impairment of sudden onset lasting more than 24 h (or leading to death), of presumed vascular origin.11 Stroke subtypes (ischemic and hemorrhagic) were further classified on the basis of computed tomography. The side of the stroke was recorded and the severity was classified according to the National Institutes of Health Stroke Scale (NIHSS).12 Epileptic seizures were defined according to the International League Against Epilepsy (ILAE).13 Seizure detection was the task of the physicians and nurses who were present during each patient’s hospital stay. Seizures were coded as early (within 7 days of the stroke) or late (occurring after 7 days). Documented stroke risk factors and relevant comorbidities were Epilepsia, 56(8):1309–1313, 2015 doi: 10.1111/epi.13062
also identified. These included arterial hypertension, diabetes, ischemic heart disease, atrial fibrillation, and pulmonary and renal diseases. Hypertension was defined as blood pressure >140/90 mm Hg at least twice while in hospital after day 1. Diabetes mellitus was defined as preprandial blood glucose >126 mg/dl on two examinations, postprandial glucose >200 mg/dl, or hemoglobin A1c (HbA1c) >8.5%. History of ischemic heart disease, atrial fibrillation, pulmonary disease, and renal disease was obtained from patients’ past and present records and from ad hoc treatments. We did not do any power calculations because no specific differences were expected between patients with and without seizures. Enrollment was stopped when a convenience sample of 30 patients with early or late seizures was identified during follow-up. Because our research hypothesis was to calculate the extra costs (if any) attributable to epileptic seizures, we controlled for other sources of cost such as disease type, severity, and risk factors. For each patient with seizures, two or more controls were identified among those without seizures and matched for age (5 years), sex, stroke type, NIHSS score at admission, and stroke risk factors. Cases and controls were followed until discharge or death (whichever came first). For each case and matched controls a number of variables were collected from the medical records. These included the main demographic findings (age and sex), the clinical features at hospital admission (stroke type and site, the NIHSS score at admission, and all relevant comorbidities), and the items indicating the health care resources consumed for the management of stroke and its complications during the acute phase and in-hospital follow-up. These include the length of hospital stay, the stay in the intensive care unit (ICU), diagnostic tests and any other test for the assessment of stroke complications and comorbidities, medical consultations, and therapeutic measures. Cost estimates were based on the Russian National Health Service perspective and its implementation in the City of Moscow, which is based on mandatory health care insurance with reimbursement to the health care providers for services and treatments for the management of all diseases. The amount of reimbursement is specific for each diagnosis and constitutes the “medical-economic standard.” These costs (“standard costs”) are calculated as the costs of hospital stay (daily cost multiplied by the number of days); drugs were included in these costs.14,15 In the real clinical situation, management was tailored to the needs of each individual patient and all the necessary additional investigations, consultations, and interventions were done. These additional costs (exceeding the standard) were calculated and evaluated separately. Unit costs of specialist consultations and laboratory and instrumental tests were estimated by applying the tariffs approved for Moscow. The total cost consisted of the costs according to the “medical-economic standard” and the additional costs.
1311 Epilepsy and Hospital Costs of Stroke Descriptive statistics were computed on each demographic features, diagnostic, and therapeutic procedure separately. Differences between cases and controls were assessed using the chi-square test and the Student’s t-test, where indicated. Total costs in patients with and without seizures were compared by univariate analyses. Post hoc analysis was also done using a generalized linear model to test the total costs in the two groups after adjusting for vital status (dead or alive), an important source of expenditures. Data were analyzed using the SAS package for PC (9.2 version; SAS Institute, Inc., Cary, NC, U.S.A.).
Results During the study, 325 consecutive patients were admitted to the Moscow hospital. On September 30, 2012, 30 patients presented seizures while in hospital. Seizures occurred on day 1 in 21 cases, on days 2–3 in five cases, days 4–6 in one case, and days 21–28 in three cases. Accordingly, 27 patients had early seizures and three late seizures. There were no cases with status epilepticus. Among patients who had no seizures on that date, 70 fulfilled the matching criteria for controls. Cases and controls were followed for median periods of, respectively, 23 days (range 2–56) and 22 days (range 8–72). The demographic and clinical characteristics of cases and controls are illustrated in Table 1. The age at stroke diagnosis ranged from 35 to 85 years in both groups. There was a slight predominance of males in both groups. Ischemic stroke in the left carotid area was predominant in cases and controls. Arterial hypertension, ischemic heart disease,
Table 1. Demographic characteristics of patients in case and control groups Patients with stroke and seizures (30) Demographics Age, years (mean SD) Male (%) Stroke type (%) Left ischemic Right ischemic Hemorrhagic Comorbidities and stroke risk factors (%) Diabetes Hypertension Ischemic heart disease Atrial fibrillation Pulmonary disease Renal disease NIHSS (mean SD)
Patients with stroke without seizure (70)
p-Value
65.9 10.6
67.8 10.9
0.38
16 (53.3)
36 (51.4)
0.92
14 (46.7) 11 (36.7) 5 (16.7)
35 (50) 25 (35.7) 10 (14.3)
0.86 0.95 0.79
atrial fibrillation, pulmonary disease, and diabetes were, in decreasing order, the most common comorbidities in both groups (Table 1). Seizures were all focal with or without secondary generalization. Fifty percent of cases (15/30) died in hospital, compared to 5.7% of controls (4/70) (p < 0.001). Among survivors, NIHSS score at discharge was 3.3 (standard deviation) 1.8 in cases versus 3.8 2.9 in controls, a nonsignificant difference. The overall hospital stay was similar in patients with and without seizures (Table 2). However, patients with seizures spent more days in the ICU and fewer days in the neurology ward. Compared to controls, patients with seizures required more computed tomography scans, x-rays and endoscopies, and specialist consultations. The overall cost of hospital stay was slightly (nonsignificantly) higher in patients with seizures and was mostly accounted for by the ICU costs (Table 3). The cost of additional (above the standard) consultations and, except for ultrasound, the cost of diagnostic tests were significantly higher among cases than controls (Table 4). The total cost was significantly higher in patients who died than in patients who were discharged alive (US$ 4173.95 vs. 1584.98 US$; p < 0.0001). After adjusting for vital status, patients with and without seizures had fairly similar cost estimates (Table S1). Table 2. Resource consumption by cases and controls Stroke with seizures (30) (mean SD) Hospital stay, days Days in neurology ward Days in ICU CT, no. Consultations (for one person, no.) X-ray studies, no. Blood and urine tests, no. Blood biochemistry tests, no. Endoscopies, no.
22.1 14.9 7.3 2.6 4.9
11.9 10.9 8.9 1.8 1.8
Stroke without seizures (70) (mean SD)
p-Value
0.34 0.03 0.03
