Factors Encouraging Internal Medicine Specialists in Japan to Move towards Certification as General Practitioners.

In Japan, a new medical specialist system started in 2018 and has established the "Comprehensive Medical Specialist" program. The Japan Medical Agency allows specially-appointed supervisors, such as specialists in particular branches of internal medicine, to transfer to the "general practitioner" program. These specialists are often considered as reserve general practitioners. In April 2016, we conducted a survey of 2,666 randomly selected specialists in 11 societies related to the Japanese Society of Internal Medicine. Of the 404 who responded (15.2% response rate), 142 (35.1%) were "certification-oriented." Logistic regression analysis with the outcome of desire for certification as a general practitioner (yes = 1) showed odds of 2.293 (95% confidence interval: 1.379-3.811) for "cannot take the necessary time to prepare" and 12.417 (95% confidence interval: 2.856-53.986) for "should be eligible to take the exam without leaving my current job." Creating an environment that allows specialists in internal medicine across various specialties to prepare for certification as a general practitioner, while continuing to work in their current positions, would help to increase the number of high-quality general practitioners to supply the need in Japan.

Point Prevalence Surveys of Antimicrobial Prescribing in a Non-Acute Care Hospital in Saitama Prefecture, Japan.

Background: The global point prevalence survey (Global-PPS) is the standard for the surveillance of prescribed antimicrobials among inpatients and provides data for the development of hospital antimicrobial stewardship programs. Aim: To evaluate the prevalence and quality of antimicrobial prescriptions using the universally standardized Global-PPS protocol in a non-acute care hospital in Saitama Prefecture, Japan. Methods: Antimicrobial prescriptions for inpatients, staying at the hospital overnight, were surveyed on three separate week days in November 2018, January 2019, and May 2019. Information on the prescribed antimicrobials on the survey target day was obtained from the in-hospital pharmacy. Survey data were collected by physicians, based on the extracted information. Patient information was anonymized and entered in the Global-PPS Web application by physicians. We report the antimicrobial use prevalence, the indication for prescription, diagnosis, the most prescribed antimicrobials, and a set of quality indicators related to antimicrobial prescribing. Results: In total, 6.7% of the surveyed inpatients (120/1796) were prescribed antimicrobials on the survey day. Sulfamethoxazole/trimethoprim was the most commonly prescribed, with 20.0% of systemic antibiotic prescriptions (ATC J01). Of all antibiotics for systemic use, up to 58.4% were Watch antibiotics, as defined by the World Health Organization AWaRe classification. The most prescribed group of systemic antibiotics was non-penicillin beta-lactam antibiotics (34.4%), followed by penicillin antibiotics in combination with beta-lactamase inhibitors (25.6%), and sulfonamides with trimethoprim (20.8%). Healthcare-associated infections and medical prophylaxis were the most common indications reported in 69.3% and 26.3% of prescriptions, respectively. The most common diagnosis for systemic antibiotic prescriptions was pneumonia (49.6%). Reasons for antimicrobial prescriptions were indicated in the medical records for 67.1% of prescriptions, and the stop/review date was documented to be 50.3%. Compliance with local guidelines reached 66.7%. Conclusions: This study highlights important challenges related to antimicrobial prescription in a highly specific, non-acute care patient population.

Blood Pressure Level and Variability During Long-Term Prasugrel or Clopidogrel Medication After Stroke: PRASTRO-I.

BACKGROUND AND PURPOSE: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. METHODS: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. RESULTS: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094-1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010-1.466]), hemorrhagic stroke (13 events, 3.247 [1.660-6.296]), ischemic events (142 events, 1.219 [1.020-1.466]), and bleeding events (47 events, 1.629 [1.172-2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220-4.225] per 10-mm Hg increase; 3.051 [2.179-4.262]; 3.276 [1.172-9.092]; 2.865 [2.042-4.011]; 2.764 [1.524-5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. CONCLUSIONS: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp; Unique identifier: JapicCTI-111582.

Significance of Nonfocal Symptoms in Patients With Transient Ischemic Attack.

Background and Purpose- Patients with transient ischemic attack (TIA) occasionally show nonfocal symptoms, such as unconsciousness, amnesia, and unsteadiness. The purpose of this study was to clarify the characteristics and prognosis of patients with TIA with nonfocal symptoms, using data from the PROMISE-TIA (Prospective Multicenter Registry to Identify Subsequent Cardiovascular Events After Transient Ischemic Attack). Methods- Patients with TIA within 7 days of onset were consecutively enrolled in the Japanese nationwide registry. Factors associated with nonfocal symptoms and 1-year risks of ischemic stroke and coronary artery diseases were assessed in multivariate-adjusted models. Results- We studied 1362 patients with TIA (879 men; mean age, 69±12 years), including 219 (16%) with nonfocal symptoms. Patients with TIA with nonfocal symptoms were more likely to show acute ischemic lesions in the posterior circulation on diffusion-weighted imaging (multivariate-adjusted odds ratio, 3.07; 95% confidence interval, 1.57-5.82) and arterial stenosis or occlusion in the posterior circulation on vascular examination (odds ratio, 1.94; 95% confidence interval, 1.19-3.09) than those without nonfocal symptoms. Although 1-year risk of ischemic stroke did not differ significantly between groups (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.37), risk of coronary artery disease was higher in patients with TIA with nonfocal symptoms (hazard ratio, 3.37; 95% confidence interval, 1.14-9.03). Conclusions- Both acute ischemic lesions and arterial stenosis and occlusion in the posterior circulation were more frequently observed in patients with TIA with nonfocal symptoms.

Selection of Oral Anticoagulants in Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Anticoagulant therapy is indicated for management of ischemic stroke patients with nonvalvular atrial fibrillation. We retrospectively investigated how oral anticoagulants were selected for ischemic stroke patients with nonvalvular atrial fibrillation. METHODS: This study included 297 stroke patients with nonvalvular atrial fibrillation admitted to our hospital between September 2014 and December 2017, and who were subsequently transferred to other institutions or discharged home. Baseline clinical characteristics were compared between patients prescribed warfarin and those prescribed direct-acting oral anticoagulants. RESULTS: In total, 280 of 297 (94.3%) patients received oral anticoagulant therapy, including 36 with warfarin, while 244 received direct oral anticoagulants. Age, percentage of heart failure, CHADS2 score before stroke onset, percentage of treatment with warfarin on admission, percentage of feeding tube at hospital discharge, and modified Rankin Scale at hospital discharge were significantly higher in the warfarin group versus the direct oral anticoagulants group, while creatinine clearance was significantly higher in the direct oral anticoagulant group. By multiple logistic regression, taking warfarin at admission and higher modified Rankin Scale at hospital discharge were associated with warfarin selection, while higher creatinine clearance was associated with direct oral anticoagulant selection (warfarin: odds ratio [OR] 7.10 [95% confidence interval {CI} 2.83-17.81]; modified Rankin Scale at hospital discharge: [OR] 1.47 [95% {CI} 1.06-2.04]; creatinine clearance: [OR] .97 [95% {CI} .95-.99]). CONCLUSIONS: Selection of oral anticoagulants in acute ischemic stroke patients with nonvalvular atrial fibrillation was influenced by warfarin use at admission, clinical severity at hospital discharge, and renal function.

Clinical Study of Intravenous, Low-Dose Recombinant Tissue Plasminogen Activator for Acute Cerebral Infarction: Comparison of Treatment within 3 Hours versus 3-4.5 Hours.

BACKGROUND: An intravenous recombinant tissue plasminogen activator (rt-PA, alteplase .6 mg/kg) for acute cerebral infarction within 3 hours of onset was approved in Japan in 2005. The treatment window was subsequently extended to within 4.5 hours of onset. However, few Japanese studies have compared the efficacy and safety of rt-PA therapy between patients treated within 3 hours and patients treated within 3-4.5 hours. METHODS: This study included 323 patients who received rt-PA for acute cerebral infarction within 3 hours or 3-4.5 hours between April 2007 and March 2017. Patients' characteristics, outcomes (modified Rankin Scale [mRS] score at 3 months), and symptomatic intracranial hemorrhage (sICH) were retrospectively investigated. RESULTS: Of the 323 patients, 219 were treated within 3 hours and 104 were treated at 3-4.5 hours. Among patients receiving rt-PA alone, 154 were treated within 3 hours (3-hour group), and 69 were treated at 3-4.5 hours (3-4.5-hour group). There was no difference in the sICH rate (3.9% versus 4.3%, respectively; P = 1.00) or mRS score of 0-1 (38.3% versus 40.6%, respectively; P = .76) between these groups. In patients receiving additional neuroendovascular therapy, 65 were in the 3-hour group and 35 were in the 3-4.5-hour group. There was no significant difference in the sICH rate (1.5% versus 0%, respectively; P = 1.00) or mRS score of 0-1 (30.8% versus 31.4%, respectively; P = 1.00) between these groups. CONCLUSIONS: Low-dose rt-PA treatment from either 3 or 3-4.5 hours after acute cerebral infarction has the same efficacy and safety.

Outcome of Acute Ischemic Stroke after the Treatment with Edaravone and 0.6 Mg/Kg Alteplase in Japanese Patients with Diabetes.

BACKGROUND: We investigated how diabetes mellitus (DM) affects the outcome of acute ischemic stroke (AIS), comparing with the outcomes in those who had hypertension (HT) and atrial fibrillation (AF). METHODS: This study was a sub-analysis of PROTECT4.5, which was previously performed as a large-scale, prospective observational study of edaravone with approximately 10,000 patients with AIS in Japan. The study patients treated with edaravone alone or edaravone + alteplase (recombinant tissue plasminogen activator [tPA]) were analyzed for their outcomes and explored for the risk factors of poor outcome, after being divided into 8 groups according to their affected complications of DM, HT, or AF in the groups treated with edaravone alone or edaravone + tPA. RESULTS: Among patients treated with edaravone alone and edaravone + tPA, the mean reduction in the National Institutes of Health Stroke Scale from baseline to 3 months after the onset was 2.0 and 4.4 in DM groups, respectively. The reduction was smaller in these groups compared with other groups (3.3-4.3 and 6.0-7.7, respectively). The logistic regression model revealed that DM was an independent risk factor for highly unfavorable outcome of modified Rankin Scale score 3-6 at 3 months after the onset, among both patients treated with edaravone alone and those treated with edaravone + tPA (odds ratio [OR]: 2.23, 95% confidential interval [CI]: 1.42-3.50 and OR: 2.05, 95% CI: 1.33-3.14, respectively). CONCLUSIONS: DM is suggested to adversely affect the outcome of AIS in Japanese patients.

The Dose of Direct Oral Anticoagulants and Stroke Severity in Patients with Acute Ischemic Stroke and Nonvalvular Atrial Fibrillation.

BACKGROUND: The severity and the functional outcome of patients with stroke occurring during off-label underdosing of direct-acting oral anticoagulants (DOACs) remain uncertain. METHODS: We studied 53 consecutive patients with acute ischemic stroke and nonvalvular atrial fibrillation who were treated with DOACs before the onset of stroke. Thirty patients were treated for primary prevention of stroke and 23 patients were treated for secondary prevention. DOAC treatments were categorized into 3 groups based on the following doses: (1) standard-dose group (n = 17), (2) low-dose group (n = 23), and (3) off-label underdose group (n = 13). RESULTS: Age was significantly older in the low-dose group than in the standard-dose group (P = .026). The standard-dose group and the low-dose group showed higher CHA2DS2-VASc scores (median, 4) compared with the off-label underdose group (median, 3). More than half of the patients had a National Institutes of Health Stroke Scale score of less than 8, and many patients had a good outcome (modified Rankin Scale score ≤1). There were no differences in stroke severity and outcome among the 3 groups. The ratio of being discharged home was the highest in the standard-dose group. CONCLUSIONS: This study shows that patients who have off-label underdosing of DOACs do not develop more severe stroke and a poorer outcome than those with the recommended dose. Careful attention to recommended doses is required for the full benefits from DOACs.

Drip-and-Ship Thrombolytic Therapy for Acute Ischemic Stroke.

BACKGROUND: Neuroendovascular therapy is a common treatment for patients with acute ischemic stroke of the anterior circulation who fail to respond to recombinant tissue plasminogen activator. However, although most hospitals can provide recombinant tissue plasminogen activator therapy, many cannot perform neuroendovascular therapy. Thus, use of a drip-and-ship treatment-liaison system allowing recombinant tissue plasminogen activator-treated patients to be transferred to facilities offering neuroendovascular therapy is important. METHODS: We retrospectively analyzed 16 drip-and-ship patients transferred to our hospital for additional neuroendovascular therapy after they received intravenous recombinant tissue plasminogen activator at prior hospitals between June 2009 and March 2017. RESULTS: The mean patient age was 68 ± 17 years. Ten patients had cardiogenic embolism and 6 had atherothrombosis. Additional neuroendovascular therapy was performed in 14 patients. Median National Institute of Health Stroke Scale and diffusion-weighted image-Alberta Stroke Program Early Computed Tomography Scores before recombinant tissue plasminogen activator therapy were 14 and 8, respectively. Occluded or stenotic lesions of the cerebral arteries were detected by magnetic resonance angiography in the internal carotid artery (n = 4), middle cerebral artery (n = 10), and basilar artery (n = 3) (1 patient had tandem lesions). Mean intervals from onset-to-recombinant tissue plasminogen activator, recombinant tissue plasminogen activator-to-our hospital (door), door-to-puncture, and onset-to-recanalization were 166, 65, 32, and 334 minutes, respectively. No patients showed symptomatic intracranial hemorrhage. CONCLUSIONS: Magnetic resonance imaging/angiography performed in previous hospitals allows initiation of reperfusion therapy immediately after transfer. Thus, drip-and-ship plus neuroendovascular therapy is a safe and useful system for treatment of patients with acute infarcts.

Comparison of Clinical Characteristics among Subtypes of Visual Symptoms in Patients with Transient Ischemic Attack: Analysis of the PROspective Multicenter registry to Identify Subsequent cardiovascular Events after TIA (PROMISE-TIA) Registry.

BACKGROUND: A transient visual symptom (TVS) is a clinical manifestation of transient ischemic attack (TIA). The aim of this study was to investigate differences in clinical characteristics among subtypes of TVS using multicenter TIA registry data. MATERIALS AND METHODS: Patients with TIA visiting within 7 days of onset were prospectively enrolled from 57 hospitals between June 2011 and December 2013. Clinical characteristics were compared between patients with 3 major subtypes of TVS (transient monocular blindness [TMB], homonymous lateral hemianopia [HLH], and diplopia). RESULTS: Of 1365 patients, 106 (7.8%) had TVS, including 40 TMB (38%), 34 HLH (32%), 17 diplopia (16%), and 15 others/unknown (14%). Ninety-one patients with 1 of the 3 major subtypes of TVS were included. Symptoms persisted on arrival in 12 (13%) patients. Isolated TVS was significantly more common in TMB than in HLH and diplopia (88%, 62%, and 0%, respectively; P < .001). Duration of symptoms was shorter in patients with TMB than those with HLH (P = .004). The ABCD2 score was significantly lower in patients with TMB compared with those with HLH and diplopia (median 2 [interquartile range 2-3] versus 3 [2-4] and 4 [2-5], respectively; P = .005). Symptomatic extracranial internal carotid artery stenosis or occlusion was seen in 14 (16%) patients, and was more frequent in TMB than in HLH and diplopia (28%, 9%, and 0%, respectively; P = .015). CONCLUSIONS: TVS was an uncommon symptom in our TIA multicenter cohort. Some differences in clinical characteristics were found among subtypes of TVS.

Bilateral carotid-anterior cerebral artery anastomoses associated with bilateral ophthalmic arteries arising from the anastomotic arteries diagnosed by magnetic resonance angiography: a case report.

Rarely, the anterior cerebral artery (ACA) arises from the ophthalmic segment of the internal carotid artery, a condition described as carotid-ACA anastomosis or infraoptic course of the ACA that generally demonstrates right-sided predominance. We diagnosed a case of bilateral anastomoses of the carotid and ACA vessels in which bilateral ophthalmic arteries arose from the origins of the anastomotic vessels using magnetic resonance (MR) angiography. Identification of rare arterial variations on MR angiography requires careful scrutiny of source images, and creation of partial volume-rendering images can aid visualization of detailed anatomic structures.

[Recombinant tissue plasminogen activator therapy for acute ischemic stroke in older patients].

AIM: As the number of aged stroke patients increases in Japan, the proportion of older patients who receive recombinant tissue plasminogen activator (rt-PA, 0.6 mg/kg) is also rising. However, the Japanese stroke guideline indicates that rt-PA therapy must be administered very carefully in older patients (i.e. ≥81 years of age) because of serious complications after the therapy. We retrospectively assessed the clinical outcomes of rt-PA therapy in older patients. METHODS: This study included 321 patients who received rt-PA therapy for acute cerebral infarction at our hospital between April 2007 and April 2017. The outcomes (modified Rankin Scale [mRS] score at 3 months after treatment) and symptomatic intracerebral hemorrhaging (sICH) were compared and analyzed between patients ≥81 years of age (group A) and those <81 years of age (group B). In addition, propensity score matching was performed for the factors shown to have significant differences by a univariate analysis in order to adjust for confounding factors, and the outcomes were compared. RESULTS: There were 58 patients in group A (18.1%) and 263 patients in group B (81.9%). The rate of favorable outcomes (mRS 0-1) was lower in group A (12.1%) than in group B (44.1%) (P<0.01). The mortality rate was higher in group A (17.2%) than in group B (4.6%) (P=0.002). No marked differences were observed between the 2 groups regarding the rate of sICH (group A, 3.4%; group B, 3.0%; P=1.00). After propensity score matching, the proportion of patients with favorable outcomes was significantly lower in group A (13.2%) than in group B (36.8%) (P=0.032). There were no marked differences in the mortality rates between the groups (group A, 17.2%; group B, 4.6%) (P=0.200), and no patients in either group had sICH. CONCLUSION: No marked differences in the incidence of ICH were observed between the older and younger groups receiving intravenous rt-PA therapy. However, in terms of efficacy, the proportion of patients with favorable outcomes was significantly lower in the older group than in the younger group.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

Timing of Treatment Initiation With Oral Anticoagulants for Acute Ischemic Stroke in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Only a few studies have addressed the optimal start time for oral anticoagulants (OACs) after acute ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). The aim of this retrospective study was to analyze the time of OAC administration after stroke onset.Methods and Results:This study included 300 patients with NVAF who had acute ischemic stroke and were treated with OACs between April 2012 and March 2016. We investigated the time at which OACs were started by anticoagulant type and the relationship between the time of OAC administration and stroke severity (the National Institutes of Health Stroke Scale [NIHSS] score on admission). Of the 300 patients, 114 and 186 patients received warfarin and direct-acting OACs (DOACs), respectively. Patients in the DOAC group had OAC initiated therapy significantly sooner (3 days) than in the warfarin group (7 days; P<0.001). With regard to stroke severity (NIHSS score <8, mild; 8-16, moderate; >16, severe), the median time for starting therapy was 2, 7, and 11 days for mild, moderate, and severe stroke, respectively. Hemorrhagic events occurred in 3 patients in the warfarin group; however, no hemorrhagic events occurred in the DOAC group. CONCLUSIONS: Our study revealed that neurologists began OACs earlier in patients with mild acute cerebral infarction. Even in patients with severe stroke, OACs were started earlier than expected.

De Novo Migraine With Aura After Surgical Repair of Aortic Coarctation.

Coarctation of the aorta (CoA) is reported to be associated with an increased risk for migraine. We describe here the case of a 13-year-old female patient who presented migraine with aura after surgical repair of CoA with a stent. As possible reasons for her condition, we postulate host responses to stent placement and/or disturbed cerebral autoregulation related to intracranial hypertension before the surgical repair and hypotension afterward, leading to hypoperfusion. This case demonstrates that de novo migraine with aura can occur after surgical repair of CoA and should be recognized as a potential complication.

Ischemic Stroke with Cardiac Pacemaker Implantation: Comparison of Physiological and Ventricular Pacing Modes.

BACKGROUND: The clinical characteristics of ischemic stroke in patients with a pacemaker (PM) are not well understood. METHODS: Forty-six ischemic stroke patients with a PM were investigated retrospectively, and the impact of different pacing modes was compared. RESULTS: The patients were divided into a physiological pacing group (n = 22) and a ventricular pacing group (n = 24). The prevalence of atrial fibrillation (AF) was significantly higher in the ventricular pacing group (36% versus 75%; P = .008). The mean left atrial dimension was relatively large in the ventricular pacing group than in the physiological pacing group (44.5 ± 6.7 mm versus 39.1 ± 8.5 mm, respectively; P = .071). Twenty-four percent of the patients were receiving anticoagulants, whereas 41% of the patients were receiving antiplatelet drugs. Cardioembolism was the most common stroke subtype in both groups. Although there was no statistically significant difference, neurological severity on admission was higher in the ventricular pacing group than in the physiological pacing group (P = .061). Functional outcomes, excluding patients with transient ischemic attack or prior stroke, significantly declined in the ventricular pacing group compared with the physiological pacing group (P = .044). CONCLUSIONS: The avoidance of the ventricular pacing mode may result in improved clinical outcomes. In patients without persistent AF, it may be important to select physiological pacing instead of ventricular pacing to decrease potential stroke severity.

Edaravone with and without .6 Mg/Kg Alteplase within 4.5 Hours after Ischemic Stroke: A Prospective Cohort Study (PROTECT4.5).

BACKGROUND: Edaravone is widely used to treat acute ischemic stroke (AIS) within 24 hours of onset. We aimed to evaluate current edaravone treatment practices and the efficacy and safety of edaravone used with recombinant tissue plasminogen activator (tPA) in AIS patients within 4.5 hours of onset. The results were compared with those of the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) study. METHODS: PROTECT4.5 was a prospective observational study conducted from April 2010 to March 2013 in Japan. The primary end points were favorable outcomes (modified Rankin Scale score [mRS] 0-1) at 3 months after onset and incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours of treatment. For comparison with SITS-ISTR, patients were categorized based on the time from onset to treatment (within 3 hours of and 3-4.5 hours after onset) and baseline National Institutes of Health Stroke Scale score (NIHSS). RESULTS: Among the 11,384 registered patients, 11,126 and 8274 patients were included in the safety and efficacy analysis populations, respectively. The proportions of patients with mRS 0-1 receiving edaravone alone and edaravone + tPA were 51.3% (95% confidence interval, 49.7%-52.8%) and 39.0% (37.6%-40.5%), respectively. The incidence of sICH within 36 hours after tPA treatment (edaravone + tPA group) was 1.6% (1.3%-2.0%). When compared with the SITS-ISTR results, those treated with edaravone + tPA appeared to show better outcomes in patients with NIHSS score ≥16. CONCLUSIONS: The efficacy and safety of edaravone combined with tPA and administered within 4.5 hours of AIS onset were demonstrated with numerically lower incidence of sICH and better outcomes.

Progressive Bilateral Vertebral Artery Dissection in a Case of Osteogenesis Imperfecta.

A 32-year-old woman with osteogenesis imperfecta (OI) was admitted to the hospital because of a right-sided occipital headache and facial paresthesia. She was diagnosed with lateral medullary syndrome due to right vertebral artery (VA) dissection. She was treated conservatively without antithrombotic therapy. She developed subarachnoid hemorrhage because of contralateral VA dissection 18 days later. This clinical course may reflect the underlying weakness of the vessel wall in OI. In patients with OI, occlusion of a unilateral VA could cause dissection and subsequent rupture of the contralateral VA. Early surgical treatment for lesions of the VA is required in such cases.

Differences in Clinical Characteristics between Patients with Transient Ischemic Attack Whose Symptoms Do and Do Not Persist on Arrival.

BACKGROUND: Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. METHODS: We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. RESULTS: Two hundred sixty-six patients (158 men, 68.0 ± 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long-duration TIA (≥60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00-3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). CONCLUSION: Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival.