Hematocrit Predicts Poor Prognosis in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

This study aims to investigate the association between HCT (Hematocrit) levels and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA); 14,832 participants from the China National Stroke Registry-III with AIS or TIA were analyzed. Participants were categorized into quartiles based on baseline HCT levels. The primary outcome was poor functional outcomes (modified Rankin Scale ≥ 3) during three months, with secondary outcomes including all-cause death, stroke recurrence, and combined vascular events. Logistic regression or Cox regression models were used to assess the relationship between HCT and clinical outcomes. Compared to the third quartile, patients in the lowest quartile group showed increased risk of poor functional outcome (adjusted OR: 1.35, 95% CI: 1.15-1.58, p < 0.001), patients in the lowest quartile had a higher risk of all-cause death (adjusted HR: 1.68, 95% CI: 1.06-2.68, p = 0.028), as did those in the highest quartile (adjusted HR: 2.02, 95% CI: 1.26-3.25, p = 0.004). Sensitivity analysis shows that the association of HCT with all-cause death weakened, while the association with poor functional outcome was strengthened after excluding patients with recurrent stroke. Our results indicated that HCT level could be used as a short-term predictor for poor functional outcomes and all-cause death in patients with AIS or TIA.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5-24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study.

BACKGROUND AND PURPOSE: Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. METHODS: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5-24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0-1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). RESULTS: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46-2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0-2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. CONCLUSION: This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5-24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Indobufen versus aspirin in patients with acute ischaemic stroke in China (INSURE): a randomised, double-blind, double-dummy, active control, non-inferiority trial.

BACKGROUND: Aspirin is recommended for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke but can lead to gastrointestinal intolerance and bleeding. Indobufen is used as an alternative antiplatelet agent in some countries, despite an absence of large-scale clinical trials for this indication. We tested the hypothesis that indobufen is non-inferior to aspirin in reducing the risk of new stroke at 90 days in patients with moderate-to-severe ischaemic stroke. METHODS: We conducted a randomised, double-blind, double-dummy, active control, non-inferiority trial at 163 tertiary and district general hospitals in China. Eligible participants were aged 18-80 years with acute moderate-to-severe ischaemic stroke (National Institutes of Health Stroke Scale score 4-18). We randomly assigned (1:1) participants within 72 h of the onset of symptoms to receive either indobufen (100 mg tablet twice per day) or aspirin (100 mg tablet once per day) for 90 days. The randomisation sequence was computer generated centrally and stratified by local participating centres. Masked local investigators assigned the random code to patients in ascending order and provided a treatment kit corresponding to the random code. The primary efficacy outcome was new stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. This primary efficacy outcome was assessed in all randomly assigned and consenting patients and in a per-protocol group (ie, all patients finishing the treatment without major violation of the trial protocol). Safety analyses were done in the safety-analysis population (ie, all patients who received at least one dose of the study drug and had a safety assessment available). We assessed the non-inferiority of indobufen versus aspirin using the one-sided upper limit of the 95% CI of the hazard ratio (HR) with a prespecified non-inferiority margin of 1·25. This trial is registered with ClinicalTrials.gov (NCT03871517). FINDINGS: This trial took place between June 2, 2019, and Nov 28, 2021. Of 84 093 patients screened, 5438 patients were randomly assigned to receive either indobufen (n=2715) or aspirin (n=2723), all of whom were included in the primary analyses. Median age was 64·2 years (IQR 56·1-70·6); 1921 (35·3%) were women and 3517 (64·7%) were men. Stroke occurred within 90 days in 213 (7·9%) patients in the indobufen group versus 175 (6·4%) in the aspirin group (HR 1·23, 95% CI 1·01-1·50; pnon-inferiority=0·44). Moderate or severe bleeding occurred in 18 (0·7%) patients in the indobufen group and in 28 (1·0%) in the aspirin group (0·63, 95% CI 0·35 to 1·15; p=0·13). Adverse events within 90 days occurred in 666 (24·5%) patients in the indobufen group and 679 (24·9%) patients in the aspirin group (p=0·73). INTERPRETATION: In patients with acute moderate-to-severe ischaemic stroke, indobufen was not non-inferior to aspirin because the upper limit of the 95% CI was greater than 1·25. Furthermore, indobufen seemed to be inferior to aspirin in reducing the risk of recurrent stroke at 90 days because the lower limit of the 95% CI was greater than 1·00. Although moderate or severe bleeding did not differ between groups, these findings do not support the use of indobufen for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke. FUNDING: Hangzhou Zhongmei Huadong Pharmaceutical and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.

BACKGROUND: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

Associations of environment and lifestyle factors with suboptimal health status: a population-based cross-sectional study in urban China.

INTRODUCTION: Suboptimal health status (SHS), an intermediate state between chronic disease and health, is characterized by chronic fatigue, non-specific pain, headaches, dizziness, anxiety, depression, and functional system disorders with a high prevalence worldwide. Although some lifestyle factors (e.g. smoking, alcohol consumption, physical exercise) and environmental factors (e.g. air quality, noise, living conditions) have already been studied, few studies can comprehensively illustrate the associations of lifestyle and environment factors with general, physical, mental, and social SHS. METHODS: A cross-sectional study was conducted among 6750 urban residents aged 14 years or over in five random cities from September 2017 to September 2018 through face-to-face questionnaires. There were 5881 valid questionnaires with a response rate of 87%. A general linear model and structural equation model were developed to quantify the effects of lifestyle behaviors and environment factors on SHS. RESULTS: The detection rates of general, physical, mental, and social SHS were 66.7, 67.0, 65.5, and 70.0%, respectively. Good lifestyle behaviors and favorable environment factors positively affected SHS (P < 0.001). Lifestyle behaviors had the largest effect on physical SHS (ß = - 0.418), but the least on social SHS (ß = - 0.274). Environment factors had the largest effect on mental SHS (ß = 0.286), but the least on physical SHS (ß = 0.225). CONCLUSIONS: Lifestyle behaviors and environment factors were important influencing factors of SHS. Physical SHS was more associated with lifestyle. Lifestyle and environment were similarly associated with mental and social SHS.

Association analysis of Suboptimal health Status: a cross-sectional study in China.

BACKGROUND: Suboptimal health status (SHS) among urban residents is commonplace in China. However, factors influencing SHS have not been thoroughly explored, especially with regard to the effects of internal factors (e.g., personality and health awareness) on SHS. METHODS: A cross-sectional study was conducted with a nationally representative sample of 5460 Chinese urban residents..SHS was measured using the Suboptimal Health Mesurement Scale Version 1.0. Demographic information, and information pertaining to lifestyle behaviors, environmental factors, and internal factors were abtained through a questionnaire. The associations between demographic information, lifestyle behaviors, environmental factors, internal factors and SHS were assessed using logistic regression. RESULTS: Of the 5460 participants (with a mean age of 41.56 ±  16.14 years), 2640 (48.4 %) were men. Out of 36 variables, 23 were significantly associated with SHS: age (odds ratio [OR]: 1.014), an education level of high school/junior college (OR: 1.443) , marital status (OR: 1.899), area of registered permanent residence (OR: 0.767), monthly household income (p < 0.001) , exposure to second-hand smoke (p = 0.001), alcohol drinking (OR: 1.284), bad eating habits (OR: 1.717), not sleeping before 11 p.m. every day (p = 0.002), spending time online more than five hours a day (OR: 1.526), having a good relationship with parents during one's growth period (OR: 0.602), living with good quality air (OR:0.817), living in not crowded conditions (OR:0.636), having a harmonious neighborhood (OR:0.775), having adequate fitness facilities (OR:0.783), one's health being affected by two-child policy (OR: 1.468) and medical policies (OR: 1.265) , high adverse quotient (OR: 0.488), many (≥3 kinds) interests and hobbies (OR: 0.617), mature and steady personality traits (OR: 0.469) , a high attention to one's health (OR: 0.833), and effective health promotion induced by leading a leisurely lifestyle (OR: 0.466) were significantly associated with SHS. CONCLUSIONS: All these variables were included demographic information, lifestyle behaviors, environmental factors and internal factors. Our study supports the benefits of controlling both internal and external factors in preventing suboptimal health.

Mediating effect of health consciousness in the relationship of lifestyle and suboptimal health status: a cross-sectional study involving Chinese urban residents.

OBJECTIVE: Suboptimal health status (SHS), a third state between good health and disease, can easily develop into chronic diseases, and can be influenced by lifestyle and health consciousness. No study has surveyed the intermediation of health consciousness on the relationship between lifestyle and SHS. This study aimed to analyse the association of lifestyle and SHS, and intermediation of health consciousness in Chinese urban residents. DESIGN: A cross-sectional face-to-face survey using a four-stage stratified sampling method. PARTICIPANTS: We investigated 5803 Chinese urban residents aged 18 years and over. We measured SHS using the Sub-Health Measurement Scale V1.0. We adopted a structural equation model to analyse relationships among lifestyle, health consciousness and SHS. We applied a bootstrapping method to estimate the mediation effect of health consciousness. RESULTS: Lifestyle had stronger indirect associations with physical (ß -0.185, 95% CI -0.228 to -0.149), mental (ß -0.224, 95% CI -0.265 to -0.186) and social SHS (ß -0.216, 95% CI -0.257 to -0.179) via health consciousness than direct associations of physical (ß -0.144, 95% CI -0.209 to -0.081), mental (ß -0.146, 95% CI -0.201 to -0.094) and social SHS (ß -0.130, 95% CI -0.181 to -0.077). Health consciousness has a strong direct association with physical (ß 0.360, 95% CI 0.295 to 0.427), mental (ß 0.452, 95% CI 0.392 to 0.510) and social SHS (ß 0.434, 95% CI 0.376 to 0.490). Ratio of mediating effect of health consciousness to direct effect of lifestyle with physical, mental and social SHS was 1.28, 1.53 and 1.66, respectively. CONCLUSIONS: Health consciousness was more important in preventing physical, mental and social SHS than lifestyle. Therefore, it might be useful in changing unhealthy lifestyle and reducing the influence of poor lifestyle on physical, mental and social SHS.

[Association analysis between personality and sub-health among urban residents aged over 14 years in 4 Chinese provinces].

OBJECTIVE: To explore the direct relationship between personality (PN) and sub-health status (SHS) and their indirect association mediated by frustration quotient (FQ) and stress event (SE). METHODS: A multiple-stage stratified sampling method was used to choose the participants, and a total of 4517 eligible urban residents were selected.ANCOVA was used to analyze the independent association between personality and SHS after adjusting the demographic characteristics and lifestyle.A structural equation model was used to analyze the associations among personality, FQ, SE and SHS.Bootstrap method was used to test the direct and indirect association between personality and SHS. RESULTS: Personality was independently associated with total sub-health (F=75.913, P < 0.001), physical sub-health (F=23.618, P < 0.001), mental sub-health (F=101.993, P < 0.001) and social sub-health (F=48.757, P < 0.001).The urban residents with the personalities characterized by anger suppression, anxiety and irritability, and impatience and competitiveness had significantly lower health scores than those with a mature and steady personality (P < 0.05).Personality was associated with FQ and SE, and the indirect association between personality and physical sub-health was mainly mediated by FQ and SE (ß=-0.110).Personality showed more a direct association (ß=-0.172) with mental sub-health and a slightly less indirect association (ß=-0.126) with mental sub-health.Personality showed a more indirect association (ß=-0.113) with social SHS and slightly less direct association (ß=-0.082) with social sub-health. CONCLUSIONS: A mature and steady personality may help to promote the general health level, while the personalities of anger suppression, anxiety and irritability, impatience and competitiveness can be associated with the occurrence of sub-health.Building a mature and steady personality has positive effects on the health in general of an individual.

[Establishment of the norms of Sub-Health Measurement Scale Version 1.0 for Chinese urban residents].

OBJECTIVE: To establish the norms of Sub-Health Measurement Scale (SHMS V1.0) for Chinese urban residents. METHODS: Using a multistage stratified sampling method, we conducted a large-scale epidemiological investigation among 15 066 urban residents sampled from 6 regions in China, including Tianjin City (north China), Guangdong Province (south China), Anhui Province (central south China), Sichuan Province (southwest China), Lanzhou City (northwest China) and Harbin City (northeast China). The mean, percentile and threshold norms were established based on the characteristics of SHMS V1.0 scores for Chinese urban residents. RESULTS: The mean and percentile norms of total, physical, mental and social sub-health of Chinese urban residents were established according to gender and different age groups (14-19, 20-29, 30-49, 50-64 and ≥65 years). The threshold norms of SHMS V1.0 divided 5 health states, namely disease, severe sub-health, moderate subhealth, mild sub-health and healthy states according to the Mean±SD and Mean±0.5SD of the converted scores. CONCLUSIONS: The norms of Sub-Health Measurement Scale (SHMS V1.0) for Chinese urban residents were established, which provides a reference for rapid screening and diagnosis of sub-health status in Chinese urban residents and facilitates further study of the prevalence and contributing factors of sub-health.