Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Miyagi Medical and Welfare Information Network: A Backup System for Patient Clinical Information after the Great East Japan Earthquake and Tsunami.

On March 11, 2011, the Great East Japan Earthquake and ensuing tsunami that hit the northeastern coastal region of Japan caused about 18,000 casualties and destroyed numerous buildings. Additionally, many medical facilities were damaged and patient medical records lost. In order to maintain patient clinical information, a prefectural medical network system, the Miyagi Medical and Welfare Information Network (MMWIN), began providing backup data storage services in 2013 for hospitals, clinics, pharmacies, and other care facilities as a precaution for upcoming disasters. This system also facilitates the sharing of clinical information trans-institutionally as long as patients provide consent for this. In the present study, we examined the development of the MMWIN and its efficiency during the 5 years from its launch, and identified general problems to maintain such a backup system. At the end of 2018, the system contained backup data from more than 11 million patients with more than 420 million data items; more than 900 facilities were MMWIN users, and the number of patients consenting to sharing their clinical information reached 90,000. The use of the system has become widespread and the accumulating data should be utilized for research in the future. Maintaining a balance between income and cost is critical to make this project independent from local government subsidies.

Group analysis and classification of working memory task conditions using electroencephalogram cortical currents during an n-back task.

Electroencephalographic studies of working memory have demonstrated cortical activity and oscillatory representations without clarifying how the stored information is retained in the brain. To address this gap, we measured scalp electroencephalography data, while participants performed a modified n-back working memory task. We calculated the current intensities from the estimated cortical currents by introducing a statistical map generated using Neurosynth as prior information. Group analysis of the cortical current level revealed that the current amplitudes and power spectra were significantly different between the modified n-back and delayed match-to-sample conditions. Additionally, we classified information on the working memory task conditions using the amplitudes and power spectra of the currents during the encoding and retention periods. Our results indicate that the representation of executive control over memory retention may be mediated through both persistent neural activity and oscillatory representations in the beta and gamma bands over multiple cortical regions that contribute to visual working memory functions.

A cavernous sinus dural arteriovenous fistula treated by direct puncture of the superior ophthalmic vein with craniotomy: illustrative case.

BACKGROUND: The authors report a case of symptomatic cavernous sinus (CS) dural arteriovenous fistula (dAVF) that was successfully treated using direct puncture of the superior ophthalmic vein (SOV) with craniotomy. CS dAVF is commonly treated using transvenous embolization (TVE), with the most common access route via the inferior petrosal sinus (IPS). However, this route is sometimes unavailable because of an occluded, hypoplastic, aplastic, or tortuous IPS. The SOV is an alternative, albeit tortuous and long, route to the CS; therefore, direct SOV puncture is occasionally performed. Direct SOV puncture is mostly percutaneous; however, in this case, it was difficult because of subcutaneous SOV narrowing. OBSERVATIONS: As the patient experienced increased intraocular pressure, decreased vision, and eye movement disorders, CS embolization was performed via direct puncture with a craniotomy because of other access difficulties. LESSONS: Several reports have described CS dAVF in patients receiving endovascular treatment via direct SOV puncture using a transorbital approach. However, to the best of the authors' knowledge, this is the first reported case of a CS dAVF treated using TVE with craniotomy. This approach is useful when the SOV cannot be reached intravenously and its distance from the epidermis is long.

[Usefulness of dynamic MRA and CTA in diagnosis and postoperative evaluation in spinal dural arteriovenous fistula: a case report].

Here we report a case of spinal dural arteriovenous fistula that was diagnosed on MRA and CTA, and then treated by endovascular embolization. A 56-year-old male presented with slowly progressive intermittent claudication and numbness of the lower extremities. T2-weighted MR imaging showed the swelling of the spinal cord with an intramedullary high signal intensity area and dilated vessels with signal flow void at the dorsal aspect of spinal cord. Dynamic MRA demonstrated the feeding artery, shunt point and the overview of dilated veins as seen with a CTA. Endovascular embolization using liquid material was performed under local anesthesia. The injection of glue included the distal feeding artery, the shunt itself and the initial part of the draining vein. A complete cure was achieved. CTA after embolization demonstrated the glue cast and the disappearance of the AV shunt and dilated veins that were visible before embolization. It was suggested that dynamic MRA and CTA are useful for the final diagnosis and postoperative evaluation of spinal dural arteriovenous fistulas.

Hemodialysis Record Sharing: Solution for Work Burden Reduction and Disaster Preparedness.

BACKGROUND: After the Great East Japan Earthquake in 2011, backup systems for clinical information were launched in Japan. The system in Miyagi Prefecture called the Miyagi Medical and Welfare Information Network (MMWIN) is used as a health information exchange network to share clinical information among various medical facilities for patients who have opted in. Hospitals and clinics specializing in chronic renal failure require patients' data and records during hemodialysis to facilitate communication in daily clinical activity and preparedness for disasters. OBJECTIVE: This study aimed to facilitate the sharing of clinical data of patients undergoing hemodialysis among different hemodialysis facilities. METHODS: We introduced a document-sharing system to make hemodialysis reports available on the MMWIN. We also recruited hospitals and clinics to share the hemodialysis reports of their patients and promoted the development of a network between emergency and dialysis clinics. RESULTS: In addition to basic patient information as well as information on diagnosis, prescription, laboratory data, hospitalization, allergy, and image data from different facilities, specific information about hemodialysis is available, as well as a backup of indispensable information in preparation for disasters. As of June 1, 2021, 12 clinics and 10 hospitals of 68 dialysis facilities in Miyagi participated in the MMWIN. The number of patients who underwent hemodialysis in Miyagi increased by more than 40%. CONCLUSIONS: Our backup system successfully developed a network of hemodialysis facilities. We have accumulated data that are beneficial to prevent the fragmentation of patient information and would be helpful in transferring patients efficiently during unpredictable disasters.

Sideway Aspiration Technique for Thrombus in a Sharply Bifurcated Branch of a Large Vessel.

Objective: Standard thrombectomy techniques, including stent retrieval and a direct aspiration first pass technique, are not effective when the occluded vessel is narrow and sharply bifurcated from the main trunk. Here, we present a new and alternative method for patients with such anatomical features and describe two cases treated by this method. Case Presentations: Case 1 was a 66-year-old woman who presented with consciousness disturbance and left hemiparesis. MRA suggested a right middle cerebral artery occlusion. Case 2 was an 86-year-old man who presented with sudden onset of consciousness disturbance; MRA indicated occlusion of the basilar artery. Both cases were successfully treated by our new method. First, we navigated a microcatheter, microguidewire, and aspiration catheter into the patent and visible branch adjacent to the occluded branch. The aspiration catheter was then carefully pulled back with continuous mechanical aspiration. When reverse blood flow from the aspiration catheter was suspended, we slightly advanced the catheter and caught the thrombus. Complete recanalization was attained in the two cases treated with this technique, which was named as sideway aspiration technique (SAT). Conclusion: Although it warrants further study, SAT may be a potentially safe and effective method for thrombectomy in cases with thrombus in a sharply bifurcated branch.

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.

Protein Nanoparticles Modified with PDGF-B as a Novel Therapy After Acute Cerebral Infarction.

Treatment options for cerebral infarction beyond the time window of reperfusion therapy are limited, and novel approaches are needed. PDGF-B is considered neuroprotective; however, it is difficult to administer at effective concentrations to infarct areas. Nanoparticles (NPs) are small and stable; therefore, we modified PDGF-B to the surface of naturally occurring heat shock protein NPs (HSPNPs) to examine its therapeutic effect in cerebral infarction. PDGF-B modified HSPNPs (PDGF-B HSPNPs) were injected 1 d after transient middle cerebral artery occlusion (t-MCAO) in CB-17 model mice. We analyzed the infarct volume and motor functional recovery at 3 and 7 d. PDGF-B HSPNPs were specifically distributed in the infarct area, and compared with HSPNPs alone, they significantly reduced infarct volumes and improved neurologic function 3 and 7 d after administration. PDGF-B HSPNP administration was associated with strong phosphorylation of Akt in infarct areas and significantly increased neurotrophin (NT)-3 production as well as reduced cell apoptosis compared with HSPNPs alone. Moreover, astrogliosis in peri-infarct area was significantly upregulated with PDGF-B HSPNPs compared with HSPNPs alone. Treatment with PDGF-B HSPNPs might be a novel approach for treating cerebral infarction.

iCOD: an integrated clinical omics database based on the systems-pathology view of disease.

BACKGROUND: Variety of information relating between genome and the pathological findings in disease will yield a wealth of clues to discover new function, the role of genes and pathways, and future medicine. In addition to molecular information such as gene expression and genome copy number, detailed clinical information is essential for such systematic omics analysis. RESULTS: In order to provide a basic platform to realize a future medicine based on the integration of molecular and clinico-pathological information of disease, we have developed an integrated clinical omics database (iCOD) in which comprehensive disease information of the patients is collected, including not only molecular omics data such as CGH (Comparative Genomic Hybridization) and gene expression profiles but also comprehensive clinical information such as clinical manifestations, medical images (CT, X-ray, ultrasounds, etc), laboratory tests, drug histories, pathological findings and even life-style/environmental information. The iCOD is developed to combine the molecular and clinico-pathological information of the patients to provide the holistic understanding of the disease. Furthermore, we developed several kinds of integrated view maps of disease in the iCOD, which summarize the comprehensive patient data to provide the information for the interrelation between the molecular omics data and clinico-pathological findings as well as estimation for the disease pathways, such as three layer-linked disease map, disease pathway map, and pathome-genome map. CONCLUSIONS: With these utilities, our iCOD aims to contribute to provide the omics basis of the disease as well as to promote the pathway-directed disease view. The iCOD database is available online, containing 140 patient cases of hepatocellular carcinoma, with raw data of each case as supplemental data set to download. The iCOD and supplemental data can be accessed at http://omics.tmd.ac.jp/icod_pub_eng.

Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older.

OBJECTIVE: We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. METHODS: We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3-6 at discharge) and mortality using multivariable analysis. RESULTS: The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2-1.7) despite a lower proportion of poor outcomes (0.84, 0.75-0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17-0.24), statin (0.63, 0.50-0.79), ozagrel sodium (0.72, 0.60-0.86), and cilostazol (0.63, 0.51-0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51-0.68), statin (0.84, 0.75-0.94), and EPA (0.83, 0.72-0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. CONCLUSIONS: In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association.

Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated. We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population. As no evidence of the gene-gene interaction for any pair of the 11 loci was shown, we constructed a prediction model for the disease using the logistic regression analysis by incorporating the number of the risk alleles for the 11 genes, as well as age, sex and body mass index as independent variables. Cumulative risk assessment showed that the addition of one risk allele resulted in an average increase in the odds for the disease of 1.29 (95% CI=1.25-1.33, P=5.4 x 10(-53)). The area under the receiver operating characteristic curve, an estimate of the power of the prediction model, was 0.72, thereby indicating that our prediction model for type 2 diabetes may not be so useful but has some value. Incorporation of data from additional risk loci is most likely to increase the predictive power.

The Influence of Age on the Outcomes of Traumatic Brain Injury: Findings from a Japanese Nationwide Survey (J-ASPECT Study-Traumatic Brain Injury).

BACKGROUND: The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients. METHODS: Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients. RESULTS: Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P < 0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at >7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P < 0.001), and incidence of acute subdural hematoma (OR, 1.89; P < 0.001) were associated with in-hospital mortality in elderly patients with TBI. CONCLUSIONS: Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin.

OBJECTIVES: This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)-associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. METHODS: We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. RESULTS: DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). CONCLUSIONS: This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies.

Interface analysis between GSVML and HL7 version 3.

In order to realize gene-based medicine, a number of key challenges must be overcome. Construction of infrastructure capable of integrating genetic and clinical information is one of those challenges. The Genomic Sequence Variation Markup Language (GSVML) and the Health Level Seven Version 3 (HL7v3) are important electronic data exchange standards for clinical genome infrastructure, and compatibility between these two standards will promote the above integration. In this study, we analyzed the interface between GSVML and HL7v3, primarily for the Clinical Genomics Domain, from a view of the GSVML, and were able to create a blueprint for a functional interface between GSVML and HL7v3. We expect that these analytical results will help accelerate the realization of gene-based medicine.

Triple-balloon shunt placement for carotid endarterectomy: a novel intraluminal shunt designed to preserve the internal and external carotid blood flow.

OBJECTIVE: To report a newly developed intraluminal triple-balloon shunt designed to preserve the blood flow of both the internal carotid artery (ICA) and the external carotid artery (ECA) during carotid endarterectomy in patients with a previous ipsilateral extracranial-intracranial bypass, in whom hemodynamic cerebral ischemia might be caused by cross-clamping at the ICA as well as the ECA. METHODS: The novel device consists of 3 silicone tubes equipped with balloons at each end. The design facilitates insertion proximally to the common carotid artery and distally to both the ICA and the ECA. RESULTS: The new shunt tube was used in 3 patients, each of whom had previously undergone ipsilateral superficial temporal artery-middle cerebral artery bypass for proximal middle cerebral artery occlusion. The blood flow of the middle cerebral artery and anterior cerebral artery was supplied independently from the ECA via the bypass and from the ICA, respectively. There were no shunt-related complications. CONCLUSIONS: This novel shunt device can be used safely and effectively in cases requiring preservation of the blood supply to both the ICA and the ECA during carotid endarterectomy.

Genomic Sequence Variation Markup Language (GSVML).

OBJECTIVE: With the aim of making good use of internationally accumulated genomic sequence variation data, which is increasing rapidly due to the explosive amount of genomic research at present, the development of an interoperable data exchange format and its international standardization are necessary. Genomic Sequence Variation Markup Language (GSVML) will focus on genomic sequence variation data and human health applications, such as gene based medicine or pharmacogenomics. DESIGN AND METHOD: We developed GSVML through eight steps, based on case analysis and domain investigations. By focusing on the design scope to human health applications and genomic sequence variation, we attempted to eliminate ambiguity and to ensure practicability. We intended to satisfy the requirements derived from the use case analysis of human-based clinical genomic applications. Based on database investigations, we attempted to minimize the redundancy of the data format, while maximizing the data covering range. We also attempted to ensure communication and interface ability with other Markup Languages, for exchange of omics data among various omics researchers or facilities. The interface ability with developing clinical standards, such as the Health Level Seven Genotype Information model, was analyzed. RESULTS: We developed the human health-oriented GSVML comprising variation data, direct annotation, and indirect annotation categories; the variation data category is required, while the direct and indirect annotation categories are optional. The annotation categories contain omics and clinical information, and have internal relationships. For designing, we examined 6 cases for three criteria as human health application and 15 data elements for three criteria as data formats for genomic sequence variation data exchange. The data format of five international SNP databases and six Markup Languages and the interface ability to the Health Level Seven Genotype Model in terms of 317 items were investigated. CONCLUSION: GSVML was developed as a potential data exchanging format for genomic sequence variation data exchange focusing on human health applications. The international standardization of GSVML is necessary, and is currently underway. GSVML can be applied to enhance the utilization of genomic sequence variation data worldwide by providing a communicable platform between clinical and research applications.