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In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10 -9 ). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10 -10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.

The incidence of large disasters has been increasing worldwide. This has led to a growing interest in disaster medicine. In this review, we report current evidence related to disasters and coronavirus disease-2019 (COVID-19) pandemic, such as cardiovascular diseases during disasters, management of disaster hypertension, and cardiovascular diseases associated with COVID-19. This review summarizes the time course and mechanisms of disaster-related diseases. It also discusses the use of information and communication technology (ICT) as a cardiovascular risk management strategy to prevent cardiovascular events. During the 2011 Great East Japan Earthquake, we used the "Disaster Cardiovascular Prevention" system that was employed for blood pressure (BP) monitoring and risk management using ICT. We introduced an ICT-based BP monitoring device at evacuation centers and shared patients' BP values in the database to support BP management by remote monitoring, which led to improved BP control. Effective use of telemedicine using ICT is important for risk management of cardiovascular diseases during disasters and pandemics in the future., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Whether rapid transportation can benefit patients with trauma remains controversial. We determined the association between prehospital time and outcome to explore the concept of the "golden hour" for injured patients., Methods and Findings: We conducted a retrospective cohort study of trauma patients transported from the scene to hospitals by emergency medical service (EMS) from January 1, 2016, to November 30, 2018, using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital time intervals were categorized into response time (RT), scene to hospital time (SH), and total prehospital time (TPT). The outcomes were 30-day mortality and functional status at hospital discharge. Multivariable logistic regression was used to investigate the association of prehospital time and outcomes to adjust for factors including age, sex, mechanism and type of injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and prehospital interventions. Overall, 24,365 patients from 4 countries (645 patients from Japan, 16,476 patients from Korea, 5,358 patients from Malaysia, and 1,886 patients from Taiwan) were included in the analysis. Among included patients, the median age was 45 years (lower quartile [Q1]-upper quartile [Q3]: 25-62), and 15,498 (63.6%) patients were male. Median (Q1-Q3) RT, SH, and TPT were 20 (Q1-Q3: 12-39), 21 (Q1-Q3: 16-29), and 47 (Q1-Q3: 32-60) minutes, respectively. In all, 280 patients (1.1%) died within 30 days after injury. Prehospital time intervals were not associated with 30-day mortality. The adjusted odds ratios (aORs) per 10 minutes of RT, SH, and TPT were 0.99 (95% CI 0.92-1.06, p = 0.740), 1.08 (95% CI 1.00-1.17, p = 0.065), and 1.03 (95% CI 0.98-1.09, p = 0.236), respectively. However, long prehospital time was detrimental to functional survival. The aORs of RT, SH, and TPT per 10-minute delay were 1.06 (95% CI 1.04-1.08, p < 0.001), 1.05 (95% CI 1.01-1.08, p = 0.007), and 1.06 (95% CI 1.04-1.08, p < 0.001), respectively. The key limitation of our study is the missing data inherent to the retrospective design. Another major limitation is the aggregate nature of the data from different countries and unaccounted confounders such as in-hospital management., Conclusions: Longer prehospital time was not associated with an increased risk of 30-day mortality, but it may be associated with increased risk of poor functional outcomes in injured patients. This finding supports the concept of the "golden hour" for trauma patients during prehospital care in the countries studied., Competing Interests: The authors have declared that no competing interests exist.

Improvements in medical treatment have contributed to rising health spending. Yet there is relatively little evidence on whether the spending increase is "worth it" in the sense of producing better health outcomes of commensurate value-a critical question for understanding productivity in the health sector and, as that sector grows, for deriving an accurate quality-adjusted price index for an entire economy. We analyze individual-level panel data on medical spending and health outcomes for 123,548 patients with type 2 diabetes in four health systems: Japan, The Netherlands, Hong Kong and Taiwan. Using a "cost-of-living" method that measures value based on improved survival, we find a positive net value of diabetes care: the value of improved survival outweighs the added costs of care in each of the four health systems. This finding is robust to accounting for selective survival, end-of-life spending, and a range of values for a life-year or fraction of benefits attributable to medical care. Since the estimates do not include the value from improved quality of life, they are conservative. We, therefore, conclude that the increase in medical spending for management of diabetes is offset by an increase in quality.

Unlike other international guidelines but in accord with the earlier Japanese Society of Hypertension (JSH) guidelines, the 2019 JSH guidelines ("JSH 2019") continue to emphasize the importance of out-of-office blood pressure (BP) measurements obtained with a home BP device. Another unique characteristic of JSH 2019 is that it sets clinical questions about the management of hypertension that are based on systematic reviews of updated evidence. JSH 2019 states that individuals with office BP < 140/90 mm Hg do not have normal BP. The final decisions regarding the diagnosis and treatment of hypertension should be performed based on out-of-office BP values together with office BP measurements. For hypertensive adults with comorbidities, the office BP goal is usually <130/80 mm Hg and the home BP goal is <125/75 mm Hg. Recommendations of JSH 2019 would be valuable for not only Japanese hypertensive patients but also Asian hypertensive patients, who share the same features including higher incidence of stroke compared with that of myocardial infarction and a steeper blood pressure-vascular event relationship., (© 2019 Wiley Periodicals, Inc.)

Introduction: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB)., Methods: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases., Results: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77)., Discussion: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.

Objectives: To investigate the treatment pattern of non-muscle invasive bladder cancer patients among urologists in Japan, Korea and Taiwan, with emphasis on compliance with important treatment guidelines., Methods: A Web-based questionnaire survey was conceived by representative members of each country's urological oncology society and was open from June 2016 to February 2017 to each society's members. Descriptive statistics and multinomial logistic regression analysis were used., Results: A total of 2334 urologists were invited and 701 responded to the survey with a response rate of 30.0%. Instruments used during transurethral resection of bladder cancer varied significantly between countries and depended on their availability. The re-transurethral resection rate for pT1 or high-grade disease >50% of the time was significantly higher in Japan than in the other two countries, but the collective rate was just 49%. The frequency of intravesical therapy in intermediate- to high-risk disease was generally consistent across countries. However, the choice of agent between chemotherapy and bacillus Calmette-Guérin was significantly different between countries. Maintenance bacillus Calmette-Guérin was used <10% of the time by 45% of respondents, the most important reasons being fear of side-effects, followed by a lack of efficacy and shortage of drug supply., Conclusions: There are significant differences between Japan, Korea and Taiwan in the management of intermediate- to high-risk non-muscle invasive bladder cancer. The results of this survey can serve as the basis for joint efforts to develop common clinical guidelines., (© 2019 The Japanese Urological Association.)

Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n = 500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n = 1,254), were genotyped by TaqMan platform. Case-control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P = 6.04 × 10(-7)), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD., (© 2015 International Society for Autism Research, Wiley Periodicals, Inc.)

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk., (Published 2014. This article is a US Government work and, as such, is in the public domain of the United States of America.)