Buflomedil for acute ischaemic stroke.

BACKGROUND: Few strategies are effective for the treatment of acute ischaemic stroke. Buflomedil is a vasoactive agent that has been used for peripheral arterial diseases. Research studies have suggested that buflomedil may have beneficial effects in people with cerebral vascular diseases, including acute ischaemic stroke, however it has not been approved for treating stroke in clinical practice. OBJECTIVES: To assess the efficacy and safety of buflomedil for the treatment of acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 4), MEDLINE (1950 to February 2014), EMBASE (1980 to February 2014), ProQuest Dissertations and Theses Database (July 2014), Web of Science (including Conference Proceedings Citation Index Science (CPCI-S)) (July 2014), and four Chinese databases (February 2014). We also searched five ongoing trials registers and reference lists of the included trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the efficacy of buflomedil in people with acute ischaemic stroke. The primary outcome of this review was long-term death or disability/dependence. Other outcomes included short-term death, short-term disability, neurological deficits, and adverse events. We included trials comparing buflomedil versus a placebo control, trials comparing buflomedil plus usual medical care versus usual medical care alone, or those comparing buflomedil plus another intervention versus that intervention alone. We excluded trials comparing buflomedil alone with other potentially active intervention(s). DATA COLLECTION AND ANALYSIS: Two review authors independently scrutinised citations, selected studies, extracted data and assessed risk of bias in the included trials. We reported risk ratios (RRs) for dichotomous data and standardised mean differences (SMDs) for continuous data. We performed meta-analysis, using a random-effects model, for death and improvement of neurological deficits. Data for disability/dependence and adverse events were not suitable for meta-analysis thus we reported these narratively. We performed subgroup analyses for time of recruitment since stroke, delivery route, daily dose, and treatment duration. MAIN RESULTS: We included 26 trials (2756 participants), all conducted in China. All participants were inpatients within the first few days after stroke onset (mean age 58 to 75 years and male proportion 45% to 80%). Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days. The study quality was generally poor and many trials were poorly reported.Only one trial reported long-term death and disability, where stroke survivors in the buflomedil group had a lower risk of suffering 'death or disability' than those in the control group (200 participants, RR 0.71, 95% confidence interval (CI) 0.53 to 0.94). All 26 trials assessed outcomes by the end of treatment (eight trials with 1056 participants reported death, one trial with 85 participants reported disability, and 26 trials with 2756 participants reported neurological deficits), but there was no robust evidence for any of these short-term outcomes. Seventeen trials (1899 participants) investigated the presence of adverse events during the treatment, of which six trials (853 participants) reported "no significant adverse event in any participants" and the other 11 trials (1046 participants) reported a total of 38 adverse events in the buflomedil group and two events in the control group. In general, for each of these outcomes the quality of evidence was low according to the GRADE principles. AUTHORS' CONCLUSIONS: There is insufficient evidence on the efficacy or safety of buflomedil to support its use for the treatment of acute ischaemic stroke. Given these uncertainties, the data support the rationale for an adequately powered RCT of buflomedil in people with acute ischaemic stroke.

Detecting atheromatous plaques in the aortic arch or supra-aortic arteries for more accurate stroke subtype classification.

INTRODUCTION: To investigate the correlations of atheromatous plaques in the aortic arch or supra-aortic arteries with intracranial arterial stenosis and carotid plaques in stroke patients, and to determine whether taking these plaques into account will reduce the proportion of patients in the undetermined etiology group. METHODS: We prospectively enrolled 308 ischemic stroke patients, whose clinical characteristics and A-S-C-O classifications were compared with analyses of intracranial arteries, carotid arteries, aortic arch, and supra-aortic arteries. RESULTS: 125(40.6%) patients had plaques in the aortic arch or supra-aortic arteries, of which 106 (84.8%) had complex plaques. No correlations were observed between these plaques and carotid plaques ( p = 0.283) or intracranial arterial stenosis ( p = 0.097). After detecting the mobile thrombi in the aortic arch and supra-aortic arteries, the proportion of patients in the atherothrombosis group was increased from 33.8% to 55.5% ( p = 0.00), whereas the proportion of patients in stroke of undetermined etiology group was decreased from 19.2% to 11.0% ( p = 0.00). DISCUSSION: Examining only the carotid and intracranial arteries may not provide adequate information about large arteries in stroke patients. Therefore, it would be better to include a search for relevant plaques in the aortic arch or supra-aortic arteries in modern stroke workup, for it may lead to more accurate stroke subtype classification and guide secondary prevention.

Etiology and Risk Factors of Posterior Circulation Infarction Compared with Anterior Circulation Infarction.

BACKGROUND: Many clinicians regard posterior circulation infarction (PCI) as different from anterior circulation infarction (ACI), leading them to apply different treatments. Few studies have validated this practice by directly comparing the etiology and risk factors of PCI and ACI. METHODS: We compared the etiology and risk factors of 2245 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. Stroke etiology in each patient was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Our sample included 482 patients (21.5%) with PCI and 1763 (78.5%) with ACI. The most frequent etiology for both infarction types was small-artery occlusion, occurring in 37.6% of patients with PCI and 37.1% of those with ACI. Cardioembolism caused infarction in a significantly smaller proportion of patients with PCI (5.4%) than in patients with ACI (13.3%; odds ratio [OR] = .373; 95% confidence interval [CI], .245-.566). Frequencies of other stroke etiologies were similar between the 2 patient groups. Analysis of risk factor frequencies in the 2 groups showed hypertension to be the most common, occurring in 47.9% of patients in either group. Multivariable analysis identified 2 factors as conferring greater risk of PCI than ACI: male gender (OR = 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR = 1.667; 95% CI, 1.275-2.180). The same analysis identified 2 factors as conferring greater risk of ACI: atrial fibrillation (OR = .530; 95% CI, .295-.951) and heart valve disease (OR = .433; 95% CI, .203-.922). Frequencies of other possible risk factors were similar between the 2 groups. CONCLUSIONS: These findings suggest that PCI and ACI are more similar than different in their etiology and risk factors and that the 2 types of infarction should be treated based more on etiology and risk factors than on their posterior or anterior localization.

Efgartigimod for generalized myasthenia gravis: A multicenter real-world cohort study in China.

OBJECTIVE: Efgartigimod, a neonatal Fc receptor antagonist, facilitates antibody degradation including pathogenic IgGs. The ADAPT study demonstrated the tolerability and efficacy of efgartigimod in the treatment of generalized myasthenia gravis (gMG). However, very limited evidence is available for the Chinese population, and it remains inconclusive about which kind of patients are selected to preferentially receive efgartigimod in real-world settings. METHODS: This multicenter cohort study included gMG patients treated at 14 neuromuscular reference centers in China. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score, immunosuppressants, and the incidence of treatment-emergent adverse events (TEAEs) were prospectively collected. RESULTS: Of the 1640 gMG admitted between September and December 2023, 61 (3.7%) received efgartigimod for at least one treatment cycle. Among them, 56 cases (92%) were anti-AChR antibody-positive, 4 were anti-MuSK antibody-positive, and 1 was seronegative. Thymoma-associated myasthenia gravis accounted for most cases (44%, 27 out of 61). The principal causes of efgartigimod initiation included MG acute exacerbation (MGAE) (48%, 29 out of 61) and myasthenic crisis (MC) (15%, 9 out of 61). Clinically meaningful improvement was rapidly achieved in 97% (58 out of 61) of patients at 1.3 ± 0.7 weeks. By week 12, the MG-ADL score reduced to 3.8 ± 4.1 (baseline:10.5 ± 5.2) for all participants, while it reduced to 4.0 ± 4.7 for MGAE and 3.8 ± 4.2 for MC, respectively. All but one TMG patient required no additional rescue therapies after efgartigimod initiation. 11.5% (7 out of 61) reported ≥1 TEAEs. INTERPRETATION: This multicenter cohort study demonstrated the efficacy of efgartigimod in rapid control of gMG. Patients with MGAE or MC would benefit from efgartigimod treatment.

[Analysis of acute stroke trials conducted in mainland China in the past 17 years].

OBJECTIVE: To evaluate the current status and trend of acute stroke randomized controlled trials (RCTs) in Mainland China. METHODS: Acute stroke RCTs were retrieved from 8 databases published in Chinese or English language from January 1996 to May 2013. Those with transient ischemic attack (TIA) or traumatic hemorrhage were excluded. Methodological items were referred to the Cochrane Collaboration's tool for assessing risk of bias. The definitions of Wade were used to assess the outcome measures. The data were processed by SPSS 16.0. Data were summarized as frequency (and %) or median and interquartile range. Difference in proportions was assessed with χ(2) test. RESULTS: A total of 13 493 RCTs were identified. The number of acute stroke RCTs increased by years, but only 52 multi-center RCTs were published. There were 13 multi-center placebo controlled drug trials. Among them, only 3 had a sample size of over 500 cases. In multi-center non-drug trials, only 3 used allocation concealment. The studied types of stroke included ischemic stroke (63.9%, 8623/13 493), intracerebral hemorrhage (30.8%, 4157/13 493) and subarachnoid hemorrhage (5.3%, 713/13 495). There were 61.5% (32/52) multi-center drug trials, including 65.6% (21/32) in Western drug treatment and 34.4% (11/32) in traditional Chinese medicine. There were 38.5% (20/52) non-drug trials including 8 physical therapy, 7 surgery and 5 acupuncture treatment. There were 2 multi-center placebo controlled drug trials and 2 multi-center non-drug trials used mortality/disability for assessing outcome measures over a follow-up period of 90 days or more. CONCLUSION: In the past 17 years in mainland China, the number of acute stroke RCTs has increased dramatically, but the high-quality trials are scarce. The future acute stroke trials should pay more attention to true randomization, blinding and better patient outcome measures.

Posterior versus anterior circulation infarction: how different are the neurological deficits?

BACKGROUND AND PURPOSE: Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. METHODS: Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. RESULTS: Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P<0.001), central facial/lingual palsy (PCI, 40.7% versus ACI, 62.2%; P<0.001), and hemisensory deficits (PCI, 36.4% versus ACI, 34.2%; P=0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horner's syndrome (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), crossed sensory deficits (3.0% versus 0%; P<0.001; PPV=100.0%; OR=3.98), quadrantanopia (1.3% versus 0%; P<0.001; PPV=100.0%; OR=3.93), oculomotor nerve palsy (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), and crossed motor deficits (4.0% versus 0.1%; P<0.001; PPV=92.3%; OR=36.04); however, all had a very low sensitivity, ranging from 1.3% to 4.0%. CONCLUSIONS: This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction.

Pathogenesis and Subtype of Intracerebral Hemorrhage (ICH) and ICH Score Determines Prognosis.

CDATA[Whether original intracerebral hemorrhage (ICH) score can be used to predict clinical outcomes in patients with SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy, systemic disease, hypertension, or undetermined) classification remains an open question. This study obtained data related to consecutive acute patients with ICH from 21 tertiary hospitals in China during January 2012 to December 2014. Using the SMASH-U method, patients were classified into 6 subtypes. Favorable functional outcome and mortality was obtained after ICH at the 3 months. We used logistic regression to evaluate the effectiveness of each risk model in predicting clinical outcome and under the receiver operating characteristic curves (ROC) to assess performance. A total of 3475 patients were included, the most common cause was hypertensive angiopathy (n=1279, 36.81%), followed by undetermined (n=1168, 33.61%), cerebral amyloid angiopathy (CAA) (n=507, 14.59%), structural vascular lesions (n=368, 10.59%), medication (n=96, 2.76%), and systemic disease (n=57, 1.64%). For good clinical outcome (mRS≤2), the ROC values of original ICH score were 0.781, 0.701, 0.718, 0.722, 0.788, and 0.771, while for the mortality in 3-month, the ROC values of original ICH score were 0.840, 0.734, 0.836, 0.722, 0.785, 0.820, and 0.734 according to SMASH-U pathogenic classification, respectively. The ability of original ICH score may be well differentiated among the 6 ICH pathogeneses. Thus, physicians should select different risk score according to different etiological ICH.

Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients. METHODS: The electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6. RESULTS: Four RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82-1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, -1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65-2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92-1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95-1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93-1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47-1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27-1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03-1.30; P=0.01). CONCLUSIONS: Based on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.

Assessment of methodological quality and outcome measures of acute stroke randomized controlled trials in China in recent 15 years.

BACKGROUND: Randomized controlled trials (RCTs) are the most important evidence to guide clinical practice in the treatment of acute stroke. This study aims to evaluate the changes of quantity and methodological quality of acute stroke RCTs in Mainland China published in recent 15 years. METHOD: We included un-confounded RCTs on acute stroke from eight databases published in Chinese or English from 1996 to 2010. General characteristics, design methodology, and outcome measures of studies were assessed. RESULTS: Totally, 9061 RCTs were identified. The number of acute stroke RCTs had increased by years, the total of trials published in 2010 was 20 times of that published in 1996. Three thousand four hundred eighty-eight trials (38.5%) used western drugs in the treatment, 3026 (33.4%) trials used traditional Chinese medicine (TCM), and 1933 (22.0%) trials used physical therapy. Ischemic stroke was the most common research subject among all trials (65.1%, 5,989). There were 541 (6.0%) RCTs using adequate randomization methods, 34 (0.4%) RCTs using adequate allocation concealment, and 195 (2.2%) using adequate blinding methods. Thirty-three (0.4%) RCTs adopted both adequate randomization methods and allocation concealment. Only 23 (0.3%) trials used all three methods of adequate randomization methods, allocation concealment, and blinding. During the 15 years, only the number of trials using adequate randomized methods and reporting adverse events had significantly increased (both P < 0.001). As for these RCTs, only the number of trials using adequate blinding method in pharmaceutical intervention was statistical differences compared with that of nondrug intervention trials (P = 0.043). Outcomes were assessed blindly in 72 trials. Death was reported by 14.2% of trials, impairment by 85.1%, disability by 22.5%, and handicap or quality of life by 0.4%. 99.7% trials reported positive results. Larger trials were more likely to use adequate randomized methods, allocation concealment and blinding methods, as well as to measure disability. Only 14 large-sample high-quality RCTs were found. CONCLUSION: During 15 years, the number of acute stroke RCTs has increased dramatically, but the quality of trials improves slowly. Most acute stroke trials used inadequate outcome measures in terms of their content, reliability, validity, blinding assessment.