Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials

Background: The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation. Methods: In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023. We included clinical trials if they were registered, randomised, and included participants with spontaneous intracranial haemorrhage and atrial fibrillation who were assigned to either start long-term use of any oral anticoagulant agent or avoid oral anticoagulation (ie, placebo, open control, another antithrombotic agent, or another intervention for the prevention of major adverse cardiovascular events). We assessed eligible trials using the Cochrane Risk of Bias tool. We sought data for individual participants who had not opted out of data sharing from chief investigators of completed trials, pending completion of ongoing trials in 2028. The primary outcome was any stroke or cardiovascular death. We used individual participant data to construct a Cox regression model of the time to the first occurrence of outcome events during follow-up in the intention-to-treat dataset supplied by each trial, followed by meta-analysis using a fixed-effect inverse-variance model to generate a pooled estimate of the hazard ratio (HR) with 95% CI. This study is registered with PROSPERO, CRD42021246133. Findings: We identified four eligible trials; three were restricted to participants with atrial fibrillation and intracranial haemorrhage (SoSTART [NCT03153150], with 203 participants) or intracerebral haemorrhage (APACHE-AF [NCT02565693], with 101 participants, and NASPAF-ICH [NCT02998905], with 30 participants), and one included a subgroup of participants with previous intracranial haemorrhage (ELDERCARE-AF [NCT02801669], with 80 participants). After excluding two participants who opted out of data sharing, we included 412 participants (310 [75%] aged 75 years or older, 249 [60%] with CHA2DS2-VASc score ≤4, and 163 [40%] with CHA2DS2-VASc score >4). The intervention was a direct oral anticoagulant in 209 (99%) of 212 participants who were assigned to start oral anticoagulation, and the comparator was antiplatelet monotherapy in 67 (33%) of 200 participants assigned to avoid oral anticoagulation. The primary outcome of any stroke or cardiovascular death occurred in 29 (14%) of 212 participants who started oral anticoagulation versus 43 (22%) of 200 who avoided oral anticoagulation (pooled HR 0·68 [95% CI 0·42–1·10]; I2=0%). Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events (nine [4%] of 212 vs 38 [19%] of 200; pooled HR 0·27 [95% CI 0·13–0·56]; I2=0%). There was no significant increase in haemorrhagic major adverse cardiovascular events (15 [7%] of 212 vs nine [5%] of 200; pooled HR 1·80 [95% CI 0·77–4·21]; I2=0%), death from any cause (38 [18%] of 212 vs 29 [15%] of 200; 1·29 [0·78–2·11]; I2=50%), or death or dependence after 1 year (78 [53%] of 147 vs 74 [51%] of 145; pooled odds ratio 1·12 [95% CI 0·70–1·79]; I2=0%). Interpretation: For people with atrial fibrillation and intracranial haemorrhage, oral anticoagulation had uncertain effects on the risk of any stroke or cardiovascular death (both overall and in subgroups), haemorrhagic major adverse cardiovascular events, and functional outcome. Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events, which can inform clinical practice. These findings should encourage recruitment to, and completion of, ongoing trials. Funding: British Heart Foundation

Linguistic Factors Affecting Moraic Duration in Spontaneous Japanese

Japanese is often referred to as a mora-timed language (Ladefoged 1975): the mora has been described as the psychological prosodic unit in the spoken language, and it is the metric unit of traditional poetry (Bloch 1950). However, it is clear that mo- rae are not strictly isochronous units (Beckman 1982). Thus, experimental studies have focused on detecting compensation effects that make average mora durations more equal through the modulation of the inherent duration of the segments involved (Han 1962; Port, Al-Ani, Maeda 1980; Homma 1981; Hoequist 1983a; 1983b; Warner, Arai 2001). Kawahara (2017) used the Corpus of Spontaneous Japanese to verify whether the dura- tional compensation effect within a /CV/ mora occurs in natural speech, in addition to read speech in the lab. He observed a statistically significant compensation effect of /CV/ morae, in which vowel duration tends to vary in response to the duration of the preced- ing consonant. However, as the same author has pointed out, the compensation is not absolute because there are several linguistic factors that potentially affect segments’ duration profiles. This study will support the idea that moraic isochrony does not occur in spontaneous Japanese by presenting empirical data on how linguistic factors can considerably affect variation in the average duration of morae

A nationwide survey on unilateral moyamoya disease in Japan

Objective Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries; compensation for occlusion results in rich arterial collaterals at the base of the brain. The clinical features of unilateral MMD, confirmed by typical angiographic evidence of MMD unilaterally and normal or equivocal contralateral findings, are not well known. To identify the clinical features of unilateral MMD in Japan, a nationwide survey was conducted. Patients and methods The questionnaire was directly mailed to 241 departments that reported treating unilateral MMD patients in a primary survey. We ascertained the sex, age, family history, clinical manifestation, radiological findings, treatments, course of the disease, and daily activity of unilateral MMD patients. Results A total of 114 departments replied to the questionnaire. The data of 203 patients (118 female and 85 male; female to male ratio 1.4:1) were registered and analyzed. The mean age was 40.2 years old with a peak occurring in the fifties. Twenty-one patients (10.7%) exhibited familial MMD. The clinical symptoms are motor weakness 57 (26.8%), headache 37 (17.4%), transient ischemic attack 35 (16.4%), and no symptom 30 (14.1%). The MMD types determined by imaging included ischemic type in 64 patients (32.5%), bleeding type in 51 (25.9%), and normal in 82 (41.6%). The development of moyamoya vessels was mild in 78 patients (43.9%) and most patients (81.1%) were accompanied with cerebral hypoperfusion. Medical treatment or vascular reconstruction was employed for more than half of the patients. Conclusion The clinical feature of unilateral MMD was revealed in this nationwide study. Unilateral MMD was predominant in adults and the development of moyamoya vessel was relatively less prevalent

Cerebral Bypass Surgery: Level of Evidence and Grade of Recommendation

BACKGROUND AND AIMS Cerebral bypasses are categorized according to function (flow augmentation or flow preservation) and to characteristics: direct, indirect or combined bypass, extra-to-intracranial or intra-to-intracranial bypass, and high-, moderate- or low-capacity bypass. We critically summarize the current state of evidence and grades of recommendation for cerebral bypass surgery. METHODS The current indications for cerebral bypass are discussed depending on the function of the bypass (flow preservation or augmentation) and analyzed according to level of evidence criteria. RESULTS Flow-preservation bypass plays an important role in managing complex intracranial aneurysms (level of evidence 4; grade of recommendation C). Flow-preservation bypass is currently only very rarely indicated in the treatment of cerebral tumors involving major cerebral arteries (level of evidence 5; grade of recommendation D). The trend has evolved in favor of partial resection and radiotherapy. To preserve the flow, the bypass is always a direct bypass.Flow-augmentation bypass is currently recommended for Moyamoya patients with ischemic symptoms and compromised hemodynamics (level of evidence 4; grade of recommendation C) and patients with hemorrhagic onset (level of evidence 1B; grade of recommendation A). Flow-augmentation bypass is currently not recommended for patients with recently symptomatic carotid artery occlusion, even in the setting of compromised cerebral hemodynamics (level of evidence 1A; grade of recommendation A), but may be considered in patients with hemodynamic failure and recurrent medically refractory symptoms as a final resort (level of evidence 5; grade of recommendation D). CONCLUSIONS The results of recent randomized clinical trials narrow the indication for cerebral bypass in the setting of ischemic cerebrovascular disease. However, cerebral bypass is still very useful for managing complex intracranial aneurysms (not amenable to selective clipping or endovascular therapies) and is the only treatment option for managing symptomatic patients with Moyamoya vasculopathy and impaired brain hemodynamics