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      Twenty-Year Change in Severity and Outcome of Ischemic and Hemorrhagic Strokes

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          Abstract

          This cohort study assesses secular changes in initial neurological severity and short-term functional outcomes of patients with acute stroke by sex using a large population.

          Key Points

          Question

          Did the initial neurological severity and functional outcomes of patients with stroke change throughout a 20-year period?

          Findings

          In this hospital-based, multicenter, prospective registry involving 183 080 patients with acute stroke, initial neurological severity showed a decrease over time in all stroke types. Functional outcome at hospital discharge improved in patients with ischemic stroke but no longer showed improvement after adjustment by reperfusion therapy and others; it did not clearly improve in patients with hemorrhagic stroke.

          Meaning

          Twenty-year changes in functional outcomes after ischemic and hemorrhagic strokes showed different trends presumably partly owing to differences in the development of acute therapeutic strategies.

          Abstract

          Importance

          Whether recent changes in demographic characteristics and therapeutic technologies have altered stroke outcomes remains unknown.

          Objective

          To determine secular changes in initial neurological severity and short-term functional outcomes of patients with acute stroke by sex using a large population.

          Design, Setting, and Participants

          This nationwide, hospital-based, multicenter, prospective registry cohort study used the Japan Stroke Data Bank and included patients who developed acute stroke from January 2000 through December 2019. Patients with stroke, including ischemic and hemorrhagic strokes, who registered within 7 days after symptom onset were studied. Modified Rankin Scale scores were assessed at hospital discharge for all patients.

          Exposure

          Time.

          Main Outcomes and Measures

          Initial severity was assessed by the National Institutes of Health Stroke Scale for ischemic stroke and intracerebral hemorrhage and by the World Federation of Neurological Surgeons grading for subarachnoid hemorrhage. Outcomes were judged as favorable if the modified Rankin Scale score was 0 to 2 and unfavorable if 5 to 6.

          Results

          Of 183 080 patients, 135 266 (53 800 women [39.8%]; median [IQR] age, 74 [66-82] years) developed ischemic stroke, 36 014 (15 365 women [42.7%]; median [IQR] age, 70 [59-79] years) developed intracerebral hemorrhage, and 11 800 (7924 women [67.2%]; median [IQR] age, 64 [53-75] years) developed subarachnoid hemorrhage. In all 3 stroke types, median ages at onset increased, and the National Institutes of Health Stroke Scale and World Federation of Neurological Surgeons scores decreased throughout the 20-year period on multivariable analysis. In ischemic stroke, the proportion of favorable outcomes showed an increase over time after age adjustment (odds ratio [OR], 1.020; 95% CI, 1.015-1.024 for women vs OR, 1.015; 95% CI, 1.011-1.018 for men) but then stagnated, or even decreased in men, on multivariate adjustment including reperfusion therapy (OR, 0.997; 95% CI, 0.991-1.003 for women vs OR, 0.990; 95% CI, 0.985-0.994 for men). Unfavorable outcomes and in-hospital deaths decreased in both sexes. In intracerebral hemorrhage, favorable outcomes decreased in both sexes, and unfavorable outcomes and deaths decreased only in women. In subarachnoid hemorrhage, the proportion of favorable outcomes was unchanged, and that of unfavorable outcomes and deaths decreased in both sexes.

          Conclusions and Relevance

          In this study, functional outcomes improved in patients with ischemic stroke during the past 20 years in both sexes presumably partly owing to the development of acute reperfusion therapy. The outcomes of patients with hemorrhagic stroke did not clearly improve in the same period.

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          Most cited references41

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          Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

          In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included.
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            Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

            Summary Background Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (−39·3 to −33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (−37·2 to −31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (−10·7 to −5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·3) prevalent cases of stroke globally in 2016; 41·1 million (38·0 to 44·3) in women and 39·0 million (36·1 to 42·1) in men. Interpretation Although age-standardised mortality rates have decreased sharply from 1990 to 2016, the decrease in age-standardised incidence has been less steep, indicating that the burden of stroke is likely to remain high. Planned updates to future GBD iterations include generating separate estimates for subarachnoid haemorrhage and intracerebral haemorrhage, generating estimates of transient ischaemic attack, and including atrial fibrillation as a risk factor. Funding Bill & Melinda Gates Foundation
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              Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment

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                Author and article information

                Journal
                JAMA Neurol
                JAMA Neurol
                JAMA Neurology
                American Medical Association
                2168-6149
                2168-6157
                6 December 2021
                January 2022
                6 December 2021
                : 79
                : 1
                : 1-9
                Affiliations
                [1 ]Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
                [2 ]Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Japan
                [3 ]Department of Neurology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
                [4 ]Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan
                [5 ]Department of Stroke Neurology, Kohnan Hospital, Sendai, Japan
                [6 ]Stroke Center, Okayama Kyokuto Hospital, Okayama, Japan
                [7 ]Department of Stroke Science, Akita Cerebrospinal and Cardiovascular Center, Akita, Japan
                [8 ]Department of Neurology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
                [9 ]Medical Corporation ISEIKAI, Osaka, Japan
                [10 ]Shimane University School of Medicine, Izumo, Shimane, Japan
                Author notes
                Article Information
                Group Information: The Japan Stroke Data Bank Investigators are listed in Supplement 2.
                Corresponding Author: Kazunori Toyoda, MD, PhD, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-shimmachi, Suita, Osaka 564-8565, Japan ( toyoda@ 123456ncvc.go.jp ).
                Accepted for Publication: October 7, 2021.
                Published Online: December 6, 2021. doi:10.1001/jamaneurol.2021.4346
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Toyoda K et al. JAMA Neurology.
                Author Contributions: Dr Nakai had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Toyoda, Sasahara, Sasaki, Miyamoto, Minematsu, Kobayashi.
                Acquisition, analysis, or interpretation of data: Toyoda, Yoshimura, Nakai, Koga, Sasahara, Sonoda, Kamiyama, Yazawa, Kawada, Sasaki, Terasaki, Miwa, Koge, Ishigami, Wada, Iwanaga, Minematsu.
                Drafting of the manuscript: Toyoda, Nakai, Sasaki, Wada, Iwanaga.
                Critical revision of the manuscript for important intellectual content: Yoshimura, Koga, Sasahara, Sonoda, Kamiyama, Yazawa, Kawada, Terasaki, Miwa, Koge, Ishigami, Miyamoto, Minematsu, Kobayashi.
                Statistical analysis: Nakai, Terasaki, Wada.
                Obtained funding: Toyoda.
                Administrative, technical, or material support: Yoshimura, Sasahara, Sonoda, Kamiyama, Miwa, Koge, Ishigami, Miyamoto, Kobayashi.
                Supervision: Yoshimura, Koga, Minematsu.
                Conflict of Interest Disclosures: Dr Toyoda reported personal fees from Daiichi Sankyo, Bayer, Bristol Myers Squibb, and Takeda outside the submitted work. Dr Koga reported honoraria from Bayer, Bristol Myers Squibb, Otsuka, Daiichi Sankyo, and Boehringer Ingelheim; research funds from Takeda, Daiichi Sankyo, Boehringer Ingelheim, Astellas Pharma, Pfizer, and Shionogi; and serves on the scientific advisory board for Ono. Dr Sonoda reported grants from Japan Society for the Promotion of Science during the conduct of the study; personal fees from Medtronic, Stryker, Medico’s Hirata, and Daiichi Sankyo; and cooperation in clinical trials from Bayer outside the submitted work. Dr Kamiyama reported personal fees from Daiichi Sankyo and Bristol Myers Squibb outside the submitted work. Dr Yazawa reported personal fees from Daiichi Sankyo, Bristol Myers Squibb, Otsuka, Medico’s Hirata, Stryker, Nestle, Abbott, Medtronic, and Mitsubishi Tanabe outside the submitted work. Dr Minematsu reported personal fees from Bayer, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, EPS Corporation, FUJIFILM Pharmaceuticals, Healios, Mitsubishi Tanabe, Nippon Chemiphar, Otsuka, Pfizer, Sanofi, and Stryker outside the submitted work. No other disclosures were reported.
                Funding/Support: This work was supported by JSPS KAKENHI (grants 19K19373 and 21K07472) and the Japan Agency for Medical Research and Development (grants 21lk0201094h0003 and 21lk0201109h0002).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Group Information: The Japan Stroke Data Bank Investigators are listed in Supplement 2.
                Article
                noi210075
                10.1001/jamaneurol.2021.4346
                8649912
                34870689
                3ff252a9-4dfb-4d74-95ff-2081dec82341
                Copyright 2021 Toyoda K et al. JAMA Neurology.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 4 September 2021
                : 7 October 2021
                Funding
                Funded by: JSPS KAKENHI
                Funded by: Japan Agency for Medical Research and Development
                Categories
                Research
                Research
                Original Investigation
                Online First
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