Sex Differences in Short-Term and Long-Term Outcomes Among Patients With Acute Ischemic Stroke in China.

BACKGROUND: Sex differences in stroke outcomes are crucial to secondary prevention, but previous reports showed inconsistent results. We aimed to explore the sex differences in stroke outcomes in the Third China National Stroke Registry, a prospective multicenter registry study. METHODS: Among the 15 166 patients enrolled between 2015 and 2018, 9038 patients with acute ischemic stroke (AIS) were included. The primary outcomes were stroke recurrence, mortality, and unfavorable functional outcome (modified Rankin Scale > 2) at 3, 6, and 12 months. Cox regression model was used for stroke recurrence and mortality and logistic regression was used for the unfavorable functional outcome, and adjusted as follows: (1) Model 1: without adjustment; (2) Model 2: adjusted for potential risk factors, National Institutes of Health Stroke Scale at admission, prestroke modified Rankin Scale, tPA (tissue-type plasminogen activator) treatment, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, and onset-to-door time; (3) Model 3: adjusted for covariates from model 2 in addition to blood pressure and blood serum covariates. Multiple imputation was used for missing values, and sensitivity analyses were conducted to describe sex differences by age groups. RESULTS: One-third (2802/9038) of the patients were women. Women were significantly older than men (64.78±10.84 versus 61.26±11.42, P<0.001). In the fully adjusted model, female patients were more likely to have unfavorable functional outcomes at 3 months (odds ratio, 1.28 [1.09-1.50]), especially among patients aged 65 years or older (odds ratio, 1.39 [1.14-1.70]), but no difference was discovered in patients aged <65 years. There were no sex differences in stroke recurrence and mortality at 3, 6, or 12 months or unfavorable functional outcomes at 6 or 12 months after adjustment. CONCLUSIONS: Compared with men, women with AIS were less likely to have favorable outcomes at 3 months in China, especially among those over 65 years of age. Experts should aim to tailor secondary prevention strategies for high-risk patients.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke.

Background and Purpose- Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods- We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates' balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results- Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95-2.20] for onset-to-door time ≤2 hours, 2.32 [2.18-2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88-3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62-1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70-1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions- Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

Atrial Fibrillation Known Before or Detected After Stroke Share Similar Risk of Ischemic Stroke Recurrence and Death.

Background and Purpose- We aim to compare the risk of 1-year ischemic stroke recurrence and death for atrial fibrillation diagnosed after stroke (AFDAS), atrial fibrillation known before stroke (KAF), and sinus rhythm (SR). Methods- From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals in the China National Stroke Registry II. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We explored the relationship between heart rhythm groups and 1-year ischemic stroke recurrence or death by using Cox regression adjusted for multiple covariates. Considering that death is a competing risk for stroke recurrence, we used the competing risks analysis of Fine and Gray and subdistribution Cox proportional hazards to test the association between heart rhythm and 1-year outcomes. Results- Among 19 604 ischemic stroke patients, 17 727 had SR, 495 AFDAS, and 1382 KAF. At 1 year, 54 (10.9%) patients with AFDAS, 182 (13.2%) with KAF, and 1008 (5.7%) with SR had recurrent ischemic strokes ( P<0.0001). Mortality was 22.0% in patients with AFDAS, 22.1% in patients with KAF, and 7.0% in patients with SR ( P<0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was higher than that of SR (adjusted subdistribution hazard ratios, 1.61; 95% CI, 1.29-2.01) but not different from that of KAF (adjusted subdistribution hazard ratio, 1.12; 95% CI, 0.87-1.45]). The adjusted risk of 1-year death for AFDAS was also higher than that of SR (hazard ratio, 1.70; 95% CI, 1.37-2.12) and not different from that of KAF (hazard ratio, 1.10; 95% CI, 0.86-1.41). Conclusions- This study showed that AFDAS had similar risk of 1-year ischemic stroke recurrence and mortality when compared with KAF and higher risk when compared with SR. The potential risk of AFDAS should be given more emphasis, and appropriate treatment is needed to achieve reduction in the incidence of stroke recurrence and mortality.

Transcription factors WRKY70 and WRKY11 served as regulators in rhizobacterium Bacillus cereus AR156-induced systemic resistance to Pseudomonas syringae pv. tomato DC3000 in Arabidopsis.

The activation of both the SA and JA/ETsignalling pathways may lead to more efficient general and broad resistance to Pst DC3000 by non-pathogenic rhizobacteria. However, the mechanisms that govern this simultaneous activation are unclear. Using Arabidopsis as a model system, two transcription factors, WRKY11 and WRKY70, were identified as important regulators involved in Induced Systemic Resistance (ISR) triggered by Bacillus cereus AR156. The results revealed that AR156 treatment significantly stimulated the transcription of WRKY70, but suppressed that of WRKY11 in Arabidopsis leaves. Furthermore, they were shown to be required for AR156 enhancing the activation of cellular defence responses and the transcription level of the plant defence response gene. Overexpression of the two transcription factors in Arabidopsis also showed that they were essential for AR156 to elicit ISR. AR156-triggered ISR was completely abolished in the double mutant of the two transcription factors, but still partially retained in the single mutants, indicating that the regulation of the two transcription factors depend on two different pathways. The target genes of the two transcription factors and epistasis analysis suggested that WRKY11 regulated AR156-triggered ISR through activating the JA signalling pathway, and WRKY70 regulated the ISR through activating the SA signalling pathway. In addition, both WRKY11 and WRKY70 modulated AR156-triggered ISR in a NPR1-dependent manner. In conclusion, WRKY11 and WRKY70 played an important role in regulating the signalling transduction pathways involved in AR156-triggered ISR. This study is the first to illustrate the mechanism by which a single rhizobacterium elicits ISR by simultaneously activating both the SA and JA/ET signalling pathways.

Replacing a piece of loop-structure in the substrate-binding groove of Aspergillus usamii ß-mannanase, AuMan5A, to improve its enzymatic properties by rational design.

To perfect the enzymatic properties of AuMan5A, a mesophilic glycoside hydrolase (GH) family 5 ß-mannanase from Aspergillus usamii, its loop-structure substitution was carried out by rational design and followed by megaprimer PCR. Based on the structural analysis and enzymatic property comparison of various ß-mannanases, a piece of loop-structure with seven amino acids between two ß-strands (ßD and ßE) in the substrate-binding groove, named "Loop DE," was speculated to be correlative to the thermostability and catalytic efficiency of GH family 5 ß-mannanases. Therefore, three AuMan5A's mutants, AuMan5A-Af, AuMan5A-An, and AuMan5A-Th, were designed by substituting a Loop DE sequence ((316)KSPDGGN(322)) of AuMan5A with the corresponding sequences of other three family 5 ß-mannanases, respectively. Then, the mutant-encoding genes, Auman5A-Af, Auman5A-An, and Auman5A-Th, were constructed as designed theoretically and then expressed in Pichia pastoris GS115. The expressed recombinant AuMan5A-Af (re-AuMan5A-Af) displayed the temperature optimum (T opt) of 75 °C, T m value of 76.6 °C and half-life (t 1/2) of 480 min at 70 °C, which were 10 and 12.1 °C higher and 48-fold longer than those of re-AuMan5A, respectively. Its catalytic efficiency (k cat/K m) was 12.7-fold that of re-AuMan5A. What is more, the site-directed mutagenesis of D320G in AuMan5A-Af was performed. The T opt and t 1/2 of expressed re-AuMan5A-Af(D320G) decreased to 70 °C and 40 min, respectively, while its k cat/K m was only 35 % of that of re-AuMan5A-Af. These results demonstrated that the mutation of G320 (in AuMan5A) into D320 (in AuMan5A-Af) through Loop DE substitution was mainly responsible for the thermostability and catalytic efficiency improvement of AuMan5A-Af.

Improvement in the thermostability of a type A feruloyl esterase, AuFaeA, from Aspergillus usamii by iterative saturation mutagenesis.

Feruloyl or ferulic acid esterase (Fae, EC 3.1.1.73) catalyzes the hydrolysis of ester bonds between polysaccharides and phenolic acid compounds in xylan side chain. In this study, the thermostability of a type A feruloyl esterase (AuFaeA) from Aspergillus usamii was increased by iterative saturation mutagenesis (ISM). Two amino acids, Ser33 and Asn92, were selected for saturation mutagenesis according to the B-factors analyzed by B-FITTER software and ΔΔG values predicted by PoPMuSiC algorithm. After screening the saturation mutagenesis libraries constructed in Pichia pastoris, 15 promising variants were obtained. The best variant S33E/N92-4 (S33E/N92R) produced a T m value of 44.5 °C, the half-lives (t1/2) of 35 and 198 min at 55 and 50 °C, respectively, corresponding to a 4.7 °C, 2.33- and 3.96-fold improvement compared to the wild type. Additionally, the best S33 variant S33-6 (S33E) was thermostable at 50 °C with a t1/2 of 82 min, which was 32 min longer than that of the wild type. All the screened S33E/N92 variants were more thermostable than the best S33 variant S33-6 (S33E). This work would contribute to the further studies on higher thermostability modification of type A feruloyl esterases, especially those from fungi. The thermostable feruloyl esterase variants were expected to be potential candidates for industrial application in prompting the enzymic degradation of plant biomass materials at elevated temperatures.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Three-dimensional finite element analysis of retracting pathological migration of the right upper central incisor with a clear aligner.

We aimed to explore the best orthodontic step distance of the right upper central incisor with mild, moderate, and severe pathological displacement achieved via a clear aligner. Three-dimensional models of maxilla-tooth-periodontal ligament clear aligner of the right upper central incisors with five different steps of 0.1, 0.125, 0.15, 0.165, 0.25 mm and three different alveolar bone heights were established via finite element analysis. We analysed the changing trends in initial displacement, the periodontal ligament, the alveolar bone, and apical stress of right upper central incisor. In the process of retraction, the right upper central incisor a movement trend of the crown deviating from the distal root to the mesial, and with the decrease of the height of the alveolar bone and the increase of the displacement, the crown would appear distal labial torsion with a deepening trend of vertical overlay.The maximum stress distribution of the periodontal ligament and alveolar bone showed a positive correlation. The overall stress distribution of the periodontal ligament and apical stress increased with decrease of alveolar bone height and the increase of alveolar bone displacement. In patients with mild, moderate, and severe pathological displacement of the right upper central incisor, the best step distance of anterior tooth retraction is 0.165, 0.15, and 0.125 mm, respectively.

Ten-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes of ischemic stroke in China: Analyses of a nationwide serial cross-sectional survey from 2005 to 2015.

BACKGROUND: Women with stroke differ from men in terms of risk factors, treatment, and outcomes. However, previous inconsistent results in China hampered the development of tailored sex-specific strategies for ischemic stroke management. We performed a nationwide serial cross-sectional survey to obtain national-level estimates to assess the 10-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes in China from 2005 to 2015. METHODS: We used a two-stage random sampling design, economic-geographical region-stratified random sampling for hospitals first and then systematic sampling for patients, to obtain a nationally representative sample of ischemic strokes in China in 2005, 2010, and 2015. We extracted data on clinical characteristics, management measures (diagnostic tests, interventions, and secondary prevention treatments), in-hospital outcomes (all-cause in-hospital mortality, discharge against medical advice [DAMA], and a composite outcome of in-hospital death and DAMA), and comorbidities. We applied weights proportional to the inverse sampling fraction of hospitals within each stratum and the inverse sampling fraction of patients within each hospital. RESULTS: A total of 26,900 ischemic stroke admissions were analyzed. Compared to men, women had a much lower prevalence of current smokers and a slightly higher prevalence of hypertension, diabetes, dyslipidemia, and atrial fibrillation at admission. Prevalence differences between sex in these cardiovascular risk factors were stable except for atrial fibrillation (decreased from 3.7% [95% CI: 1.8% to 5.7%] to 1.3% [95% CI: 0.5% to 2.0%]) and current smoker (increased from -18.0 [95% CI: -20.2% to -15.9%] to -25.6% [95% CI: -26.6% to -24.6%]). From 2005 to 2015, in-hospital management and outcomes were improved both for women and men, and sex differences in cerebrovascular assessment, cervical vessels assessment, and transthoracic echocardiography/transesophageal echocardiography were improved as well. However, women increased more slowly than men in the administration of clopidogrel (from 0.3% [95% CI: -0.9% to 1.4%) to -7.3% [95% CI: -8.7% to -6.0%]) and aspirin plus clopidogrel (0.3% [95% CI: -5.0% to 1.1%] to -5.0% [95% CI: -6.2% to -3.9%]). CONCLUSION: Compared to men, women patients with ischemic stroke had a steadily higher prevalence of cardiovascular risk factors, a slower increase rate in the administration of key secondary prevention drugs, and comparable in-hospital outcomes. More effort should be paid to the treatment and control of cardiovascular risk factors and also to the prescription of antiplatelets at discharge for women.

Clinical characteristics, in-hospital management, and outcomes of patients with in-hospital vs. community-onset ischaemic stroke: a hospital-based cohort study.

Background: Lack of high-quality national-level data on in-hospital ischaemic stroke hinders the development of tailored strategies for this subgroup's identification, treatment, and management. Methods: We analyzed and compared clinical characteristics, in-hospital management measures, and outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), disability at discharge, and in-hospital complications between in-hospital and community-onset ischaemic stroke enrolled in the Chinese Stroke Center Association registry from August 2015 to December 2022. Findings: The cohort comprised 14,948 in-hospital and 1,366,898 community-onset ischaemic stroke patients. In-hospital ischaemic stroke exhibited greater stroke severity, higher prevalence of comorbidities, more pre-admission medications, and had suboptimal management measures, for example, the onset-to-needle time within 4.5 h (83.3% vs. 93.1%; difference, -9.8% [-11.4% to -8.3%]), and antithrombotics at discharge (78.6% vs. 90.0%; difference, -11.4% [95% CI, -12.1% to -10.7%]). After adjusting for covariates, in-hospital ischaemic stroke remains associated with higher risks of unfavorable outcomes, including in-hospital death/DAMA (13.9% vs. 8.6%; adjusted risk difference [aRD], 2.2% [95% CI, 1.8%-2.7%]; adjusted odds ratio [aOR], 1.35 [95% CI, 1.25-1.45]), MACE (12.6% vs. 6.5%; aRD, 4.1% [95% CI, 3.5%-4.7%]; aOR, 1.68 [95% CI, 1.52-1.85]), and complications (23.7% vs. 12.1%; aRD, 6.5% [95% CI, 5.1%-7.9%]; aOR, 1.72 [95% CI, 1.64-1.80]), except for disability at discharge (41.1% vs. 33.1%; aRD, 0.4% [95% CI, -1.7% to 2.5%]; aOR, 0.99 [95% CI, 0.88-1.11]). Interpretation: In-hospital ischaemic stroke demonstrated more severe strokes, worse vascular risk profiles, suboptimal management measures, and worse outcomes compared to community-onset ischaemic stroke. This emphasizes the urgent need for improved hospital systems of care and targeted quality improvement initiatives for better outcomes in in-hospital ischaemic stroke. Funding: National Key R&D Programme of China and Beijing Hospitals Authority.

Short-term effect of PM2.5 on stroke in susceptible populations: A case-crossover study.

BACKGROUND: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia. METHODS: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities. RESULTS: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF (n = 15,430), hypertension (n = 138,220), diabetes (n = 43,737), or hyperlipidemia (n = 16,855) were assessed separately. A 10 µg/m3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively. CONCLUSION: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

U-shaped association between low-density lipoprotein cholesterol levels and risk of all-cause mortality mediated by post-stroke infection in acute ischemic stroke.

During the acute stage of ischemic stroke, it remains unclear how to interpret the low low-density lipoprotein cholesterol (LDL-C) level. We aimed to evaluate the association between LDL-C levels, post-stroke infection, and all-cause mortality. 804,855 ischemic stroke patients were included. Associations between LDL-C levels, infection, and mortality risk were estimated by multivariate logistic regression models and displayed by restricted cubic spline curves. Mediation analysis was performed under counterfactual framework to elucidate the mediation effect of post-stroke infection. The association between LDL-C and mortality risk was U-shaped. The nadir in LDL-C level with the lowest mortality risk was 2.67 mmol/L. Compared with the group with LDL-C = 2.50-2.99 mmol/L, the multivariable-adjusted odds ratio for mortality was 2.22 (95% confidence intervals (CI): 1.77-2.79) for LDL-C <1.0 mmol/L and 1.22 (95% CI: 0.98-1.50) for LDL-C ≥5.0 mmol/L. The association between LDL-C and all-cause mortality was 38.20% (95% CI: 5.96-70.45, P = 0.020) mediated by infection. After stepwise excluding patients with increasing numbers of cardiovascular risk factors, the U-shaped association between LDL-C and all-cause mortality and the mediation effects of infection remained consistent with the primary analysis, but the LDL-C interval with the lowest mortality risk increased progressively. The mediation effects of infection were largely consistent with the primary analysis in subgroups of age ≥65 years, female, body mass index <25 kg/m2, and National Institutes of Health Stroke Scale ≥16. During the acute stage of ischemic stroke, there is a U-shaped association between LDL-C level and all-cause mortality, where post-stroke infection is an important mediating mechanism.

Temporal trends and rural-urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey.

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Effectiveness of a Quality Improvement Intervention on Reperfusion Treatment for Patients With Acute Ischemic Stroke: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. Objective: To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China. Design, Setting, and Participants: In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020. Interventions: Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team. Main Outcomes and Measures: The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2. Results: All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals. Trial Registration: ClinicalTrials.gov Identifier: NCT03578107.

Dysphagia screening and pneumonia after subarachnoid hemorrhage: Findings from the Chinese stroke center alliance.

BACKGROUND AND PURPOSE: Dysphagia is common and is associated with aspiration pneumonia. However, little is known about the prevalence of and factors influencing dysphagia screening (DS) and pneumonia after subarachnoid hemorrhage (SAH). METHODS: We used data on SAH patients admitted to 1476 hospitals from the China Stroke Center Alliance (CSCA) from August 2015 to July 2019 to analyze the rates of DS and pneumonia. We then conducted univariate and multivariable analyses to examine the relationship between DS and pneumonia. RESULTS: Among 4877 SAH patients who were eligible for DS and had complete data on pneumonia status, 3527 (72.3%) underwent DS, and 1006 (20.6%) developed pneumonia. Compared with patients without pneumonia, patients with pneumonia were older (mean: 63.4 vs. 57.8 years of age), had lower Glasgow Coma Scale (GCS) scores at admission (mean: 13.5 vs. 14.3), were more likely to have dysphagia (15.2% vs. 3.3%), and were more likely to have undergone aneurysm isolation (19.1% vs. 10.0%). In multivariable analyses, factors independently associated with a higher risk of pneumonia were dysphagia [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.85-4.98], age (OR, 1.50 per 10-year increase; 95% CI, 1.40-1.60), male sex (OR, 1.23; 95% CI, 1.02-1.49), arrival at the hospital by emergency medical services (OR, 1.36; 95% CI, 1.16-1.58), nimodipine treatment (OR, 1.42; 95% CI, 1.11-1.81), endovascular embolization of aneurysms (OR, 1.23; 95% CI, 1.03-1.47), cerebral ventricular shunt placement (OR, 2.24; 95% CI, 1.41-3.54), and treatment at a higher grade hospital (OR, 1.44; 95% CI, 1.21-1.71). CONCLUSION: More than a quarter of patients with SAH did not have documented DS, while one-fifth developed pneumonia. DS performance was associated with a lower risk of pneumonia. Randomized controlled trials may be needed to determine the effectiveness of DS.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

External validation of ABCD series scores for predicting early stroke events following transient ischemic attack in a large nationwide registry.

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA). Patients and methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I. Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability.

Thrombolysis, time-to-treatment and in-hospital outcomes among young adults with ischaemic stroke in China: findings from a nationwide registry study in China.

BACKGROUND AND PURPOSE: We aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke. METHODS: We analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age). RESULTS: Of 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score. CONCLUSION: Young adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes.

China Stroke Statistics: an update on the 2019 report from the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations.

China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18-69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (<0.1%), 2604 (0.5%), 1250 (1.2%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 231 519 (36.1%)) of the stroke cases were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (891 103 (26.1%)) and new rural cooperative medical schema (543 108 (15.9%)). The leading risk factor was hypertension (57.3% for IS, 69.9% for ICH and 44.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.4% for IS, 34.6% for ICH and 29.7% for SAH). In-hospital death/discharge against medical advice rate was 8.5%, ranging from 6.0% for IS to 20.6% for SAH. The median and IQR of length of stay was 9.0 (6.0-13.0) days, ranging from 10.0 (7.0-13.0) in IS to 14.0 (8.0-22.0) in ICH. Similar data from 2847 secondary public hospitals or private hospitals in the HQMS were also reported. Data from HQMS showed that higher proportions of interprovincial admission to other provinces were seen in Inner Mongolia, Anhui, Tibet and Beijing. Higher proportions of interprovincial admission from other provinces were seen in Beijng, Tianjin, Shanghai and Ningxia. Data from 323 601 strokes from 1337 hospitals in the Chinese Stroke Center Alliance during 2019 demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.78±0.20, 0.69±0.27 and 0.60±0.31, respectively.