• anticoagulation
• antiplatelet
• intracranial dissection
• ischemic stroke
• subarachnoid hemorrhage

• Acute ischemic stroke
• Intravenous thrombolysis
• Mechanical thrombectomy
• Regional disparity
• Rural
• Rurality
• Social epidemiology
• Tissue plasminogen activator
• Urban

• Humans
• Female
• Male
• Ischemic Stroke/therapy
• Japan/epidemiology
• Retrospective Studies
• Aged
• Middle Aged
• Thrombolytic Therapy/methods
• Thrombolytic Therapy/statistics & numerical data
• Treatment Outcome
• Aged, 80 and over
• Rural Population/statistics & numerical data
• Thrombectomy/methods
• Thrombectomy/statistics & numerical data
• Healthcare Disparities
• Prognosis
• Follow-Up Studies

• Humans
• Arginine/analogs & derivatives
• Pipecolic Acids/therapeutic use
• Pipecolic Acids/administration & dosage
• Sulfonamides/therapeutic use
• Tissue Plasminogen Activator/therapeutic use
• Platelet Aggregation Inhibitors/therapeutic use
• Stroke/drug therapy
• Thrombolytic Therapy
• Fibrinolytic Agents/therapeutic use
• Fibrinolytic Agents/administration & dosage
• Drug Therapy, Combination

• Quzhou City Science and Technology Research Project in 2023

• Argatroban
• acute ischemic stroke
• early neurological deterioration
• meta-analysis
• stroke
• systematic review

• Activities of daily living
• Administrative data
• Disease modifying therapy
• Multiple sclerosis
• Neuromyelitis optica
• Real-world data

• Humans
• Multiple Sclerosis/epidemiology
• Multiple Sclerosis/therapy
• Neuromyelitis Optica/epidemiology
• Neuromyelitis Optica/therapy
• Retrospective Studies
• Patient Admission
• Japan/epidemiology

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.

• DPC
• National Hospital Organization in Japan
• big data
• database
• diagnosis procedure combination
• linkage
• real-world data
• validation

• is not funded by a specific project grant

Argatroban is a novel direct thrombin inhibitor that has been used for treatment of acute ischemic stroke (AIS). To our knowledge, no systematic analysis has assessed the efficacy and safety of argatroban for treatment of AIS.

To evaluate the efficacy and safety of argatroban for treatment of AIS.

Cochrane Library, Medline, PubMed, and Web of Science were searched to retrieve all studies associated with argatroban and AIS. Effective rate, adverse events rate, and 95% confidence intervals were calculated and pooled using meta-analysis methodology.

We only found four randomized controlled studies, comprising 354 cases with 213 in the argatroban group and 141 in the control group. Great heterogeneity was found in the four studies (c² = 11.44, I² = 74%, P = 0.01). Subgroup analysis could not be performed because of the absence of detailed data. The two most recent studies showed acceptable heterogeneity (c² = 1.56, I² = 36%, P = 0.21). Our analysis showed that argatroban was not more effective than the control therapy in the acute phase of ischemic stroke (Z = 0.01, P = 0.99). Argatroban did not increase the risk of bleeding compared with the control group (c² = 0.37, I² = 0%, P = 0.54, Z = 0.80, P = 0.42).

Patients with AIS might not benefit from argatroban and combination therapy with argatroban does not increase bleeding tendency.

• Argatroban
• Anticoagulation agents
• Acute ischemic stroke
• Thrombin
• Thrombolysis
• Meta-analysis

• Anticoagulation
• Argatroban
• Early neurological deterioration
• Intracranial atherosclerosis
• Single subcortical infarction

• Arginine/analogs & derivatives
• Drug Therapy, Combination
• Humans
• Intracranial Arteriosclerosis/diagnostic imaging
• Intracranial Arteriosclerosis/drug therapy
• Pipecolic Acids/therapeutic use
• Platelet Aggregation Inhibitors/therapeutic use
• Stroke, Lacunar/diagnostic imaging
• Stroke, Lacunar/drug therapy
• Sulfonamides/therapeutic use
• Treatment Outcome

• Examination
• Heart failure
• Hospital
• Medication
• Performance measure
• Secondary prevention

• Argatroban
• Bleeding
• Neurological functions
• Stroke

Chronic subdural hematoma (CSDH) is a frequently observed disease in neurosurgical practice. Although first snowfall has been considered to increase the onset of CSDH, few reports have assessed the relationship between snowfall and CSDH. In this study, we aimed to investigate the relationship between CSDH onset and first snowfall events.

This retrospective study was based on the Japanese Diagnosis Procedure Combination inpatient database from July 1, 2010, to March 31, 2016, and on the global observation of snowfall events in Japan obtained from the Japan Meteorological Agency. We used a binomial approximation to evaluate the average number of CSDH patients after first snowfall events compared with that before first snowfall events. We calculated the odds ratio of CSDH onset on the first snowfall.

We identified 8526 CSDH patients from the database. A total of 5573 (65.4%) were observed before first snowfall events, and 2953 (34.6%) after first snowfall events. The first snowfall of winter was significantly associated with a reduction in the occurrence of CSDH (odds ratio, 0.53; 95% confidence interval; 0.51–0.55). In subgroup analysis, only the first snowfall in October was not associated with reduction in the occurrence of CSDH.

First snowfall events did not affect the onset of CSDH in Japan.

• Chronic subdural hematoma
• Epidemiology
• Neurosurgery
• Snowfall
• Trauma

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antithrombins/therapeutic use
• Arginine/analogs & derivatives
• Drug Therapy, Combination
• Female
• Humans
• Intention to Treat Analysis
• Male
• Middle Aged
• Pipecolic Acids/therapeutic use
• Single-Blind Method
• Stroke/drug therapy
• Sulfonamides
• Tissue Plasminogen Activator/therapeutic use
• Young Adult
• Randomized Controlled Trials as Topic

• Endoscopic transsphenoidal surgery
• Epidemiology
• Microscopic transsphenoidal surgery
• Nationwide inpatient database
• Transcranial surgery

Recently, direct oral anticoagulants have been introduced for venous thromboembolism (VTE), which might change the management strategies of VTE. However, there have been limited data on the current real‐world practice pattern for VTE in Asian countries.

The JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases\xF6Diagnosis Procedure Combination) is a nationwide claim database from 1022 hospitals in Japan between April 2012 and March 2017. We identified 54 369 patients who were hospitalized with a diagnosis of VTE at admission based on the International Classification of Diseases, Tenth Revision (ICD‐10) code. The mean age was 69.1±15.6 years, 59% were women, and mean body mass index was 23.5±5.0 kg/m². The proportion of patients with deep vein thrombosis decreased over time from 72% in 2012 to 38% in 2017. After the release of direct oral anticoagulants, the proportion of patients receiving direct oral anticoagulants increased dramatically among patients with anticoagulation therapy at discharge with the use of edoxaban, rivaroxaban, and apixaban in 35%, 22%, and 27% of patients, respectively, in 2017. On the other hand, the proportion of patients receiving warfarin decreased from 94% in 2012 to 15% in 2017. The median length of a hospital stay decreased over time from 20 days in 2012 to 13 days in 2017 in patients with pulmonary embolism, and from 14 days in 2012 to 12 days in 2017 in patients with deep vein thrombosis. The median cost of hospitalization for pulmonary embolism moderately decreased over time, whereas that for deep vein thrombosis slightly decreased over time.

A nationwide claim‐based database provided the current practice pattern for VTE in Japan, which revealed dynamic changes after the release of direct oral anticoagulants.

URL: http://www.umin.ac.jp. Unique identifier: UMIN000037868.

• deep vein thrombosis
• direct oral anticoagulant
• pulmonary embolism
• venous thromboembolism

• AHA Scientific Statements
• critical care
• disease management
• emergency medical services
• secondary prevention
• stroke
• therapeutics

• Brain Ischemia/therapy
• Humans
• Practice Guidelines as Topic
• Stroke/therapy

The JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination) is a nationwide claims database comprised of the Japanese DPC/Per Diem Payment System. This study aimed to investigate the relationship between prescription rates of guideline‐directed medications in each hospital and in‐hospital mortality among patients with acute myocardial infarction.

A total of 61 838 Japanese patients from 741 hospitals with acute myocardial infarction between 2012 and 2013 were enrolled. The relationship between prescription rates of 4 guideline‐directed medications for acute myocardial infarction and in‐hospital mortality was analyzed. There were variations in the prescription ratio of β‐blockers on admission (median prescription rate 23% [interquartile range 11% to 38%]) and at discharge (51% [36% to 63%]), and of angiotensin converting enzyme/receptor blocker (60% [47% to 70%]). The highest prescription rate quartile of each medication was associated with a significantly lower mortality compared with the lowest prescription rate quartile (aspirin on admission, incidence rate ratio 0.67 [95% CI 0.61‐0.74], P<0.001; aspirin at discharge, incidence rate ratio 0.50 [95% CI 0.46‐0.55], P<0.001; β‐blocker on admission, 0.83 [0.76‐0.92], P<0.001; β‐blocker at discharge, 0.78 [0.71‐0.85], P<0.001; angiotensin converting enzyme/receptor blocker, 0.68 [0.62‐0.75], P<0.001; statin, 0.63 [0.57‐0.70], P<0.001). The composite prescription score was inversely associated with in‐hospital mortality (β coefficient=−0.48, P<0.001) and was closer to the plateau in the high‐score range (median mortality for composite prescription scores of 6, 15, and 24 were 10.6%, 6.8%, and 4.6%, respectively).

The prescription rates of guideline‐directed medications for treatment of Japanese acute myocardial infarction patients were inversely associated with in‐hospital mortality.

• acute myocardial infarction
• medication
• quality indicators

• Access site bleeding
• Acute coronary syndrome
• Instrumental variable
• Propensity score
• Trans-radial approach

Thrombin aggravates ischemic stroke and activated protein C (APC) has a neuroprotective effect. Both proteases interact with protease-activated receptor 1, which exhibits functional selectivity and leads to G-protein- and β-arrestin-mediated-biased signal transduction. We focused on the effect of β-arrestin in PAR-1-biased signaling on endothelial function after stroke or high-fat diet (HFD). Thrombin had a rapid disruptive effect on endothelial function, but APC had a slow protective effect. Paralleled by prolonged MAPK 42/44 signaling activation by APC via β-arrestin-2, a lower cleavage rate of PAR-1 for APC than thrombin was quantitatively visualized by bioluminescence video imaging. HFD-fed mice showed lower β-arrestin-2 levels and more severe ischemic injury. The expression of β-arrestin-2 in capillaries and PDGF-β secretion in HFD-fed mice were reduced in penumbra lesions. These results suggested that β-arrestin-2-MAPK-PDGF-β signaling enhanced protection of endothelial function and barrier integrity after stroke.

In patients with chronic kidney disease (CKD), low body mass index (BMI) is associated with high mortality. This relationship in emergently hospitalized CKD patients is unknown. We investigated the association between obesity and short-term mortality in emergently admitted patients with dialysis-independent CKD (DI-CKD) with and without infection. This retrospective cohort study examined Diagnosis Procedure Combination data of 26103 emergently hospitalized DI-CKD patients. Patients were divided into 8 groups according to their BMI and the presence of infectious diseases. The primary outcome was in-hospital death within 100 days. Cox proportional hazards models adjusted for baseline characteristics showed that low BMI was associated with the outcome both in infected and in non-infected patients (reference group as non-infected and medium BMI [24–26 kg/m²] group): infected and the lowest BMI (≤20 kg/m²) group, hazard ratio (HR) 1.82 (95% confidence interval 1.51, 2.19); non-infected and the lowest BMI group, 1.39 (1.16, 1.67). When patients were stratified according to presence of diabetes mellitus (DM), patients with DM showed that low BMI was associated with the outcome both in infected and in non-infected patients, whereas in non-DM patients, this relationship was attenuated in the non-infected group. For emergently hospitalized CKD patients with infection, high BMI was associated with lower mortality irrespective of the DM status. For non-infected patients, the effects of obesity for in-hospital mortality were modified by the DM status.

• Argatroban
• atherothrombotic infarction
• edaravone
• lacunar infarction
• noncardioembolic stroke
• ozagrel

• AHA Scientific Statements
• secondary prevention
• stroke
• therapeutics

• American Heart Association
• Brain Ischemia/diagnosis
• Brain Ischemia/therapy
• Emergency Medical Services/methods
• Emergency Medical Services/organization & administration
• Emergency Medical Services/standards
• Female
• Hospitalization
• Humans
• Male
• Stroke/diagnosis
• Stroke/therapy
• Time Factors
• United States

• Mechanical ventilation
• Mortality
• Tetanus
• Tracheostomy

• Acute stroke
• antiplatelet
• clopidogrel
• loading
• neurologic deterioration

• Aged
• Aged, 80 and over
• Brain/diagnostic imaging
• Brain/drug effects
• Brain Ischemia/blood
• Brain Ischemia/diagnostic imaging
• Brain Ischemia/drug therapy
• Clinical Decision-Making
• Clopidogrel
• Disease Progression
• Female
• Humans
• Japan
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Nerve Degeneration
• Neuroprotective Agents/administration & dosage
• Neuroprotective Agents/adverse effects
• Odds Ratio
• Patient Selection
• Platelet Aggregation Inhibitors/administration & dosage
• Platelet Aggregation Inhibitors/adverse effects
• Propensity Score
• Retrospective Studies
• Ticlopidine/administration & dosage
• Ticlopidine/adverse effects
• Ticlopidine/analogs & derivatives
• Time Factors
• Treatment Outcome

Validation of recorded data is a prerequisite for studies that utilize administrative databases. The present study evaluated the validity of diagnoses and procedure records in the Japanese Diagnosis Procedure Combination (DPC) data, along with laboratory test results in the newly-introduced Standardized Structured Medical Record Information Exchange (SS-MIX) data.

Between November 2015 and February 2016, we conducted chart reviews of 315 patients hospitalized between April 2014 and March 2015 in four middle-sized acute-care hospitals in Shizuoka, Kochi, Fukuoka, and Saga Prefectures and used them as reference standards. The sensitivity and specificity of DPC data in identifying 16 diseases and 10 common procedures were identified. The accuracy of SS-MIX data for 13 laboratory test results was also examined.

The specificity of diagnoses in the DPC data exceeded 96%, while the sensitivity was below 50% for seven diseases and variable across diseases. When limited to primary diagnoses, the sensitivity and specificity were 78.9% and 93.2%, respectively. The sensitivity of procedure records exceeded 90% for six procedures, and the specificity exceeded 90% for nine procedures. Agreement between the SS-MIX data and the chart reviews was above 95% for all 13 items.

The validity of diagnoses and procedure records in the DPC data and laboratory results in the SS-MIX data was high in general, supporting their use in future studies.

•

Validity of DPC and SS-MIX data was tested using chart review results as references.

• Administrative data
• Diagnosis
• Laboratory data
• Procedure
• Validation