1.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
2.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
3.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
4.Stroke-Specific Predictors of Major Bleeding in Anticoagulated Patients With Stroke and Atrial Fibrillation: A Nationwide Multicenter Registry-Based Study
Darda CHUNG ; Tae-Jin SONG ; Bum Joon KIM ; Sung Hyuk HEO ; Jin-Man JUNG ; Kyungmi OH ; Chi Kyung KIM ; Sungwook YU ; Kwang Yeol PARK ; Jeong-Min KIM ; Jong-Ho PARK ; Man-Seok PARK ; Joon-Tae KIM ; Yang-Ha HWANG ; Yong-Jae KIM ; Jong-Won CHUNG ; Oh Young BANG ; Gyeong-Moon KIM ; Woo-Keun SEO ; Jay Chol CHOI
Journal of Clinical Neurology 2023;19(5):429-437
Background:
and Purpose The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs).
Methods:
Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival.
Results:
Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050).
Conclusions
This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.
5.Initiation of Guideline-Matched Oral Anticoagulant in Atrial Fibrillation-Related Stroke
Mi-Yeon EUN ; Jae-Young KIM ; Yang-Ha HWANG ; Man-Seok PARK ; Joon-Tae KIM ; Kang-Ho CHOI ; Jin-Man JUNG ; Sungwook YU ; Chi Kyung KIM ; Kyungmi OH ; Tae-Jin SONG ; Yong-Jae KIM ; Bum Joon KIM ; Sung Hyuk HEO ; Kwang-Yeol PARK ; Jeong-Min KIM ; Jong-Ho PARK ; Jay Chol CHOI ; Jong-Won CHUNG ; Oh Young BANG ; Gyeong-Moon KIM ; Woo-Keun SEO
Journal of Stroke 2021;23(1):113-123
Background:
and Purpose To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF).
Methods:
Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered.
Results:
Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups.
Conclusions
ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.
6.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
7.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
8.Status Epilepticus as the Initial Manifestation of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome
Joong-Goo KIM ; Chul-Hoo KANG ; Jay Chol CHOI ; Jiyong SHIN ; Min-Ju KIM ; Jung-Hwan OH
Journal of the Korean Neurological Association 2020;38(4):276-280
Mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS) is a multisystem mitochondrial disorder that is rarely observed in adulthood. We report a case of MELAS syndrome diagnosed in a 22-year-old man presented with status epilepticus (SE) without a preceding stroke-like episode. Genetic testing revealed a mutation of heteroplasmic m.3243A>G. MELAS should be suspected in patients with recurrent, uncontrolled SE with unexplained severe lactic acidosis.
9.The Epidemiology of Fracture in Patients with Acute Ischemic Stroke in Korea
Kyung Bok LEE ; Jung Gon LEE ; Beom Joon KIM ; Jun Yup KIM ; Keon Joo LEE ; Moon Ku HAN ; Jong Moo PARK ; Kyusik KANG ; Yong Jin CHO ; Hong Kyun PARK ; Keun Sik HONG ; Tai Hwan PARK ; Soo Joo LEE ; Mi Sun OH ; Kyung Ho YU ; Byung Chul LEE ; Jae Kwan CHA ; Dae Hyun KIM ; Joon Tae KIM ; Jun LEE ; Jeong Ho HONG ; Sung Il SOHN ; Dong Eog KIM ; Jay Chol CHOI ; Min Ju YEO ; Wook Joo KIM ; Jae Eun CHAE ; Ji Sung LEE ; Juneyoung LEE ; Hee Joon BAE ;
Journal of Korean Medical Science 2019;34(22):e164-
BACKGROUND: Patients who survive an acute phase of stroke are at risk of falls and fractures afterwards. However, it is largely unknown how frequent fractures occur in the Asian stroke population. METHODS: Patients with acute (< 7 days) ischemic stroke who were hospitalized between January 2011 and November 2013 were identified from a prospective multicenter stroke registry in Korea, and were linked to the National Health Insurance Service claim database. The incidences of fractures were investigated during the first 4 years after index stroke. The cumulative incidence functions (CIFs) were estimated by the Gray's test for competing risk data. Fine and Gray model for competing risk data was applied for exploring risk factors of post-stroke fractures. RESULTS: Among a total of 11,522 patients, 1,616 fracture events were identified: 712 spine fractures, 397 hip fractures and 714 other fractures. The CIFs of any fractures were 2.63% at 6 months, 4.43% at 1 year, 8.09% at 2 years and 13.00% at 4 years. Those of spine/hip fractures were 1.11%/0.61%, 1.88%/1.03%, 3.28%/1.86% and 5.79%/3.15%, respectively. Age by a 10-year increment (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.17–1.30), women (HR, 1.74; 95% CI, 1.54–1.97), previous fracture (HR, 1.72; 95% CI, 1.54–1.92) and osteoporosis (HR, 1.44; 95% CI, 1.27–1.63) were independent risk factors of post-stroke fracture. CONCLUSION: The CIFs of fractures are about 8% at 2 years and 13% at 4 years after acute ischemic stroke in Korea. Older age, women, pre-stroke fracture and osteoporosis raised the risk of post-stroke fractures.
Accidental Falls
;
Asian Continental Ancestry Group
;
Epidemiology
;
Female
;
Hip Fractures
;
Humans
;
Incidence
;
Korea
;
National Health Programs
;
Osteoporosis
;
Prospective Studies
;
Risk Factors
;
Spine
;
Stroke
10.In-Hospital and Post-Discharge Recovery after Acute Ischemic Stroke: a Nationwide Multicenter Stroke Registry-base Study
Min Uk JANG ; Jihoon KANG ; Beom Joon KIM ; Jeong Ho HONG ; Min Ju YEO ; Moon Ku HAN ; Byung Chul LEE ; Kyung Ho YU ; Mi Sun OH ; Kyung Chan CHOI ; Sang Hwa LEE ; Keun Sik HONG ; Yong Jin CHO ; Jong Moo PARK ; Jae Kwan CHA ; Dae Hyun KIM ; Tai Hwan PARK ; Kyung Bok LEE ; Soo Joo LEE ; Jun LEE ; Joon Tae KIM ; Dong Eog KIM ; Jay Chol CHOI ; Juneyoung LEE ; Ji Sung LEE ; Philip B GORELICK ; Hee Joon BAE
Journal of Korean Medical Science 2019;34(36):e240-
BACKGROUND: Using data from a large national stroke registry, we aimed to investigate the incidence and determinants of in-hospital and post-discharge recovery after acute ischemic stroke and the independence of their occurrence. METHODS: In-hospital recovery was defined as an improvement of 4 points or > 40% in the National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge. Post-discharge recovery was defined as any improvement in the modified Rankin Scale (mRS) score from discharge to 3 months after stroke onset. Two analytic methods (multivariate and multivariable logistic regression) were applied to compare the effects of 18 known determinants of 3-month outcome and to verify whether in-hospital and post-discharge recovery occur independently. RESULTS: During 54 months, 11,088 patients with acute ischemic stroke meeting the eligibility criteria were identified. In-hospital and post-discharge recovery occurred in 36% and 33% of patients, respectively. Multivariate logistic regression with an equality test for odds ratios showed that 7 determinants (age, onset-to-admission time, NIHSS score at admission, blood glucose at admission, systolic blood pressure, smoking, recanalization therapy) had a differential effect on in-hospital and post-discharge recovery in the way of the opposite direction or of the same direction with different degree (all P values < 0.05). Both in-hospital and post-discharge recovery occurred in 12% of the study population and neither of them in 43%. The incidence of post-discharge recovery in those with in-hospital recovery was similar to that in those without (33.8% vs. 32.7%, respectively), but multivariable analysis showed that these 2 types of recovery occurred independently. CONCLUSION: Our findings suggest that, in patients with acute ischemic stroke, in-hospital and post-discharge recovery may occur independently and largely in response to different factors.
Blood Glucose
;
Blood Pressure
;
Humans
;
Incidence
;
Logistic Models
;
National Institutes of Health (U.S.)
;
Odds Ratio
;
Prognosis
;
Registries
;
Smoke
;
Smoking
;
Stroke

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