To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Intracranial Hemorrhage, Hypertensive/drug therapy* ; Nonprescription Drugs ; Stroke

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Intracranial Hemorrhage, Hypertensive/drug therapy* ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic

Adult ; Aged ; Basal Ganglia ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Intracranial Hemorrhage, Hypertensive ; drug therapy ; etiology ; Male ; Middle Aged ; Phytotherapy

OBJECT: It is reported that spontaneous subcortical intracerebral hemorrhage consists about 10 to 44% of spontaneous intracerebral hemorrhage. Recently, spontaneous subcortical intracerebral hemorrhage due to the complication of the systemic disease has been increasing, and the selection of management strategy according to the cause of hemorrhage closely affected the management outcome. This study was designed to analyze the cause of spontaneous subcortical intracerebral hemorrhage and the outcome in order to establish the appropriate management strategy. SUBJECT: One hundred and seventy-nine cases of spontaneous subcortical intracerebral hemorrhage managed at Yonsei University Hospital from January 1998 to December 2000 were included in this study. Patients who suffered from subcortical intracerebral hemorrhage due to the ruptured intracranial aneurysm were excluded. The patient's sex, age, mental state on admission, neurologic condition, past history, systemic disease related to hemorrhage, location of hemorrhage, the diagnosis of intracranial or systemic disease, treatment methods, and clinical outcome were analyzed. Consciousness on admission was evaluated and scored based on Glasgow Coma Eye Motor Scale (GCEMS), which was the sum of eye response score and motor response score of the Glasgow Coma Scale. Patients were categorized into 4 groups according to GCEMS: Group 1 (10 points), Group 2 (8, 9 points), Group 3 (5-7 points), and Group 4 (2-4 points). The clinical outcome of the patient was evaluated based on Glasgow outcome scale (GOS). Differences in diagnostic procedure were present depending on the condition of the patients, thus the final diagnostic procedure was used to diagnose the reason behind bleeding. When accurate diagnosis was difficult to perform, the reasons with the highest likelihood were chosen. RESULTS: The patients corresponding to each group were as follow: 79 (44.1%) in Group 1, 35 (19.6%) in Group 2, 27 (15.1%) in Group 3, and 38 (21.2%) in Group 4. Fifty-five patients (30.7%) were hypertensive intracerebral hemorrhage, 45 patients (25.1%) had anticoagulant therapy and thrombocytopenia due to the systemic disease and bleeding diathesis after anticancer drug therapy, 23 patients (12.8%) had brain tumor including the metastatic tumor, 19 patients (10.6%) had arteriovenous malformation, 18 patients (10.1%) had postinfarct hemorrhages, 5 patients (2.8%) had infective endocarditis, 2 patients (1.1%) had cerebral vasculitis. Conservative treatment was done in 115 patients (64.2%), open craniotomy in 31 patients (17.3%), and catheter insertion in 33 patients (18.4%). Group 1 mainly had conservative treatment (58 patients, 73.4%), Group 2 and 3 had 12 patients (37.1%) and 16 patients (59.3%) each underwent open craniotomy respectively. In Group 4, conservative treatment was done for 24 patients (63.2%), and open craniotomy was done for only one patients among 14 patients treated surgically. Overall clinical outcome was: 77 patients (43.0%) in GOS 5, 21 (11.7%) in GOS 4, 14 (7.8%) in GOS 3, 11 (6.1%) in GOS 2, and 56 patients (31.3%) died. Poor neurological state (low GCEMS) on admission was closely related to mortality (Group 1, 7.6%; Group 2, 22.8%; Group 3, 45.0%; Group 4, 78.9%). CONCLUSION: The major causes of spontaneous subcortical intracerebral hemorrhage were hypertension, metastatic brain tumor, vascular malformation, and the bleeding tendency due to the systemic disease, complication of the anticancer drug, anticoagulant, and thrombolytics therapy. Conservative treatment could be considered for the patients with GCEMS 10, removal of hematoma by open craniotomy or catheter insertion for the patients with GCEMS 5-9, and the catheter insertion or deferring the active treatment could be considered for the patients with GCEMS 2-4.
Arteriovenous Malformations ; Brain Neoplasms ; Catheters ; Cerebral Hemorrhage* ; Coma ; Consciousness ; Craniotomy ; Diagnosis ; Disease Susceptibility ; Drug Therapy ; Endocarditis ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hematoma ; Hemorrhage ; Humans ; Hypertension ; Intracranial Aneurysm ; Intracranial Hemorrhage, Hypertensive ; Mortality ; Thrombocytopenia ; Vascular Malformations ; Vasculitis, Central Nervous System

OBJECTIVETo investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH).

METHODSThis was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded.

RESULTSAfter 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups (P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group (P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 (P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment (P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment (P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group.

CONCLUSIONThe integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.

Blood Circulation ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Hematoma ; blood ; complications ; drug therapy ; Humans ; Intracranial Hemorrhage, Hypertensive ; blood ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Stroke ; blood ; drug therapy ; Treatment Outcome