S1 Supplemental Methods
Study design
The participating hospitals of the Fukuoka Stroke Registry (FSR) are Kyushu University Hospital, National Hospital Organization Kyushu Medical Center, National Hospital Organization Fukuoka–Higashi Medical Center, Fukuoka Red Cross Hospital, St. Mary’s Hospital, Steel Memorial Yawata Hospital, and Japan Labor Health and Welfare Organization Kyushu Rosai Hospital. All participating hospitals are located in Fukuoka Prefecture, Japan.
The FSR database comprises demographic characteristics, past medical history, prestroke functional status, findings of physical examinations and laboratory data during
hospitalization, information on prestroke and poststroke medications, information on all other interventions subsequent to stroke onset, and a description of the poststroke clinical course (including survival, stroke recurrence, and complications).1, 2 Among all consecutive stroke patients who were hospitalized in the participating hospitals, 86% consented to participate in a follow-up study as a prospective cohort. For patients in this cohort, we prospectively collected data during hospitalization and performed the follow-up study after their discharge.
In addition, we retrospectively collected the anonymized data of the remaining patients from their hospital records; these patients were analyzed as a retrospective cohort.
Study patients
This study included consecutive patients who suffered acute ischemic stroke (including transient ischemic stroke) and were hospitalized in the participating hospitals within 7 days of onset. Stroke was defined as sudden onset of nonconvulsive and focal neurological deficits persisting for more than 24 hours, and transient ischemic stroke was defined as deficits persisting for less than 24 hours. Stroke was diagnosed based on computed tomography or magnetic resonance imaging.
To investigate the association between sex and risk of acute infections, we defined acute infections as infections that occurred during hospitalization (acute stroke treatment in hospital or poststroke rehabilitation in inpatient rehabilitation facility). Because exact dates of
infection onset during the course of hospitalization were often difficult to determine, we limited the analyses on acute infections to patients with hospitalization duration ≤30 days to exclude infections that occurred beyond the first 30 days after stroke onset.
Clinical assessments
Baseline characteristics were defined and categorized based on previously used criteria.
Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic pressure ≥90 mm Hg in the chronic phase; or as current treatment with antihypertensive drugs. Diabetes mellitus was defined as any of the following: fasting blood glucose concentration ≥7.0 mmol/L, random blood glucose concentration ≥11.1 mmol/L, positive 75-g oral glucose
S2 tolerance test result, or glycated hemoglobin A1c concentration ≥6.5% on 2 different
daysduring hospitalization or in the chronic phase;3 or as current treatment with oral
hypoglycemic agents or insulin. Dyslipidemia was defined as either low-density lipoprotein cholesterol level ≥3.62 mmol/L, high-density lipoprotein cholesterol level <1.03 mmol/L, or triglyceride level ≥1.69 mmol/L in the chronic phase; or as current treatment with
antihyperlipidemic drugs. Atrial fibrillation was defined as any type of atrial fibrillation diagnosed based on previous or in-hospital electrocardiographic findings. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. The estimated glomerular filtration rate was calculated using the equations proposed by the
Japanese Society of Nephrology as follows: estimated glomerular filtration rate (mL/min/1.73 m2)=194×serum creatinine (mg/dL)−1.094×age (years)−0.287 in males and 194×serum creatinine (mg/dL)−1.094×age (years)−0.287×0.739 in females.4 Body mass index was calculated as weight in kg/(height in m2). Prior stroke was defined as any ischemic or hemorrhagic stroke that occurred before the index stroke. Prestroke functional status was evaluated with the modified Rankin Scale (mRS) score, where patients with prestroke mRS scores ≥2 were considered to be functionally dependent before the index stroke.5 Neurological severity was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score. Severe stroke was defined as an NIHSS score ≥8 on admission.6 Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, ischemic stroke was first classified into the following subtypes: small-vessel occlusion, large-artery atherosclerosis, cardioembolism, stroke of other determined etiology, and stroke of undetermined etiology on admission.7 These
subtypes were then dichotomized into cardioembolisms and non-cardioembolisms (i.e., large- artery atherosclerosis, small-vessel occlusion, and other). Reperfusion therapy included the use of endovascular therapy with thrombectomy, angioplasty, stenting, or intra-arterial thrombolysis during the hyperacute stage; or intravenous thrombolysis with recombinant tissue plasminogen activator, urokinase, or both. All characteristics were reviewed by a member of the FSR steering committee.
Study outcomes
In the prospective cohort, information on clinical outcomes was recorded prospectively during hospitalization for the index stroke, and after discharge data were collected by follow- up interviews of patients or their relatives, performed by trained research nurses using a standardized interview form. All research nurses were blinded to the patients’ clinical background. All information related to the events of interest, i.e. deaths and poststroke complications for this study, was reviewed by FSR event adjudication committee members, who were also blinded to the patients’ clinical background. When needed, additional information on the events was sought from the hospitals or other health care providers. To validate the outcome data as accurately as possible, the event adjudication committee
S3 members also reviewed all available clinical data, including hospital records, autopsy data, and general practitioner records.
In the retrospective cohort, information on deaths and poststroke complications was collected from hospital records. Because no data were available after discharge for patients in the retrospective cohort, these patients were treated as lost to follow-up at the time of discharge.
References
e-1. Kamouchi M, Matsuki T, Hata J, et al. Prestroke glycemic control is associated with the functional outcome in acute ischemic stroke: the Fukuoka Stroke Registry. Stroke
2011;42:2788-2794.
e-2. Kumai Y, Kamouchi M, Hata J, et al. Proteinuria and clinical outcomes after ischemic stroke. Neurology 2012;78:1909-1915.
e-3. Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus, Seino Y, Nanjo K, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 2010;1:212-228.
e-4. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009;53:982-992.
e-5. Di Carlo A, Lamassa M, Baldereschi M, et al. Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry. Stroke 2003;34:1114-1119.
e-6. Gall SL, Donnan G, Dewey HM, et al. Sex differences in presentation, severity, and management of stroke in a population-based study. Neurology 2010;74:975-981.
e-7. Adams HP, Jr., Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.