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Abstract In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; P trend

Background/Aims Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. Methods The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. Results In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p

IntroductionIt remains unclear which therapy contributes to atopic dermatitis (AD) remission and to what extent. We aimed to clarify which therapy contributes to the treatment of AD by investigating the time-to-remission and remission hazard ratios for each therapy using real-world data.MethodsThis retrospective cohort study included 110 patients diagnosed with AD after their first visit to the Department of Dermatology at Fukuoka University Hospital between 2016 and 2022. The patients were categorized into six treatment groups: 1) topical treatment alone or topical treatment plus 2) ultraviolet light, 3) oral steroids, 4) oral cyclosporine, 5) dupilumab, and 6) oral Janus kinase inhibitors (JAKi). The topical therapy alone group served as the control, and the hazard ratios for remission (Investigator’s Global Assessment [IGA] 0/1) were calculated.ResultsForty patients achieved remission, while 70 did not (IGA ≥2) with the first treatment regimen. A multivariate Cox proportional hazards analysis adjusted for age, sex, and severity at the first visit (IGA) revealed that the hazard ratios for remission were 4.2 (95% confidence interval (C.I.): 1.28–13.83, p = 0.018) for the oral cyclosporine group, 5.05 (95% C.I.: 1.96–13, p = 0.001) for the dupilumab group, and 67.56 (95% C.I.: 12.28–371.68, p < .0001) for the oral JAKi group. The median time to remission was 3 months for JAKi, cyclosporine, and steroid was shorter than 6 months for dupilumab. No serious adverse events were observed.ConclusionOral therapy with small molecules requires a shorter duration to achieve remission. However, long-term safety and recurrence are important indicators.

Abstract Background and aims Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. Methods INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP]

Background: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40–79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006–2008). Among men who returned for follow-up (2009–2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. Results: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). Conclusion: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

Background Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46–76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and β-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.

Introduction: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome, and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. Methods: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate

Abstract To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03–1.62) for 3rd quartile group and 1.39 (1.10–1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.

The Miyako Islands (with a population of approximately 50,000) are located in southwestern Japan, with a subtropical oceanic climate. This isolated location permitted a retrospective population-based epidemiological study of subarachnoid hemorrhage. We retrospectively enrolled 110 consecutive patients from 2010 to 2019 using the subarachnoid hemorrhage database at Okinawa Miyako Hospital, which is the only local facility with neurosurgeons. We calculated the incidence of subarachnoid hemorrhage standardized to the entire Japanese population. The seasonal distribution of subarachnoid hemorrhage onset and patients' epidemiological characteristics were also investigated. The standardized annual incidence of subarachnoid hemorrhage was 21.4 per 100,000 population, as reported previously in Japan. The patients' mean age was 62.1 ± 15.4 years, and women constituted 60.9%. Anterior communicating artery aneurysms were most common. The endovascular treatment for ruptured aneurysms was increasing as standard levels in Japan. The rates of symptomatic vasospasm and secondary hydrocephalus requiring additional neurosurgical treatment were 2.7% and 19.1%, respectively. The mortality rate was 23.6%. The percentage of patients with a modified Rankin scale score of 0-2 at discharge was 55.5%. There were no differences in the frequency of subarachnoid hemorrhage associated with seasonal distribution or climatic factors. The incidence, baseline characteristics, and clinical outcomes of subarachnoid hemorrhage in the Miyako Islands were similar to those in other regions of Japan. There are preferable epidemiological backgrounds for further practical clinical research.

Background/Aims The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. Methods This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. Results For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p

Objective We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population.Setting Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan.Participants A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed.Primary and secondary outcome measures Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3–16 U/L in men and 3–13 U/L in women), group 2 (17–21 U/L in men and 14–16 U/L in women), group 3 (22–29 U/L in men and 17–22 U/L in women) and group 4 (30–428 U/L in men and 23–268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies).Results After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p

Aim. To identify the risk factors for bruises and fractures from falls in patients with overactive bladder (OAB). Methods. We evaluated 1136 patients with OAB and aged ≥50 years who visited our hospital. Age, sex, frequency of nocturnal urination, and urinary incontinence type were investigated in the 360 eligible patients. Patients were divided into three groups: those patients without falls (no-fall group), those with fall bruises (bruise group), and those with fall fractures (fracture group). The risk factors for bruises and fractures in patients with OAB were evaluated using the logistic regression analysis. In addition, association between the bruises or fractures from falls and the behavior around urination during the night was investigated. Results. The multivariate logistic regression analysis showed that female sex (odds ratio (OR) 2.888, p = 0.030) and nocturnal urination frequency ≥3 times/night (OR vs. ≤2 times/night, 2.940; p = 0.040) were significantly associated with bruises. Nocturnal urination frequency ≥3 times/night (OR vs. ≤2 times/night, 2.835; p = 0.026) and urge incontinence (OR 3.415, p = 0.016) were significantly associated with fractures. Behavior around urination during the night was significantly associated with fractures (p = 0.009). Conclusion. In the real-world clinical setting, increasing nocturnal urination frequency is a common risk factor for bruises and fractures. Also, female sex and urge incontinence were the risk factors for bruises and fractures, respectively. OAB patients with urge incontinence would especially require aggressive intervention to prevent fractures during night-time voiding.

Stay-at-home strategies taken during the COVID-19 pandemic changed our lifestyle drastically. Although marital status and household size are important social determinants of health that affect lifestyle, their impacts on lifestyle during the pandemic are still unclear. We aimed to evaluate the association between marital status, household size, and lifestyle changes during the first pandemic in Japan. Questionnaire surveys on lifestyle changes from before to during the first COVID-19 pandemic were conducted on October 2020 in Japan. Classified into age groups, multivariable logistic regression analysis was performed to examine the combined association of marital status and household size on lifestyle, adjusted for potential confounders including socioeconomic factors. In our prospective cohort study, 1928 participants were included. Among older participants, the singles living alone were likely to perceive more unhealthy lifestyle changes (45.8%), compared with the married (33.2%), and significantly associated with at least one unhealthy change [adjusted odds ratio (OR): 1.81, 95% confidence interval (CI): 1,18-2.78], mainly due to decreased physical activity and increased alcohol consumption. Meanwhile, the younger participants showed no significant association between marital status, household size, and unhealthy changes, while those living alone had 2.87 times higher odds of weight gain (≥ 3 kg) than the married (adjusted OR: 2.87, 95% CI: 0.96-8.54) during the pandemic. Our findings suggest that older singles living alone are potentially vulnerable subgroups to drastic social changes which warrant special attention to prevent adverse health outcomes and additional burden on health systems in the following future.

Abstract We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA‐CKD study, a population‐based retrospective cohort study that used annual health check‐up data of residents from Iki Island, Japan. After the exclusion of 1881 with l

Abstract The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR)

Abstract Background Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). Methods A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of

Abstract Elderly cancer patients requiring surgical treatment are increasing, and the deterioration of quality of life and shortening of healthy life expectancy due to postoperative complications represent major problems. This study investigated the current status of medical treatment, including perioperative evaluations, for elderly cancer patients requiring surgical treatment at cancer treatment facilities nationwide. A total of 436 cancer care facilities around Japan were invited to participate in this web-based survey regarding management of cancer patients ≥ 65 years old who had undergone surgical treatment in 2018. A total of 919 department heads from 245 facilities agreed to participate. Although most respondents answered that performance status, preoperative examinations, and comorbidities were important when deciding on a treatment plan, age, Geriatric Assessment (GA), and guidelines were "not important" for > 10% of all respondents. GA was familiar to 195 department heads (21%), and awareness of GA was significantly lower among respondents from medical education institutions than the other types of hospitals (18.5% vs 26.3%; P = 0.006). This large survey revealed that the use of GA is not widespread, and its awareness in medical education institutions remains low. We believe that accumulating evidence of geriatric oncology surgery is an urgent issue in Japan.

Objectives The COVID-19 pandemic has had an impact on people’s lifestyles such as causing body weight changes. This study examined associations among lifestyle changes and body weight during the COVID-19 pandemic among the Japanese population.Design A cross-sectional study.Setting A nationwide survey of the general Japanese population.Participants Total participants were 2244 men and women, of which 911 young/middle-aged (30–69 years old) and 899 older adults (70 years and older) were analysed separately.Outcome Changes in lifestyle (physical activity, dietary habits and alcohol intake) and body weight during the first wave of COVID-19 in spring 2020.Results Under the COVID-19 pandemic, 24.1% and 10.1% of Japanese respondents reported weight gain and reduction, respectively. Multivariable-adjusted stepwise logistic regression analyses revealed that the young/middle-aged respondents in the group increased body weight, weight gain was significantly associated with decrease in physical activity (OR 4.01, 95% CI 2.83 to 5.69) and both increase (OR 5.82, 95% CI 3.85 to 8.80) and decrease (OR 2.73, 95% CI 1.52 to 4.93) in eating between meals. In the group that decreased body weight, body weight reduction was significantly associated with increase in physical activity (OR 3.66, 95% CI 1.94 to 6.90), decrease in eating between meals (OR 5.97, 95% CI 3.11 to 11.48) and both increase and decrease in alcohol intake in the young/middle age. For the older adults, body weight gain was higher in women than in men, and significantly associated with higher quartile of regional COVID-19 infection, decrease in physical activity (OR 2.98, 95% CI 1.98 to 4.49), increase in home-cooked meals and increase in eating between meals (OR 4.22, 95% CI 2.55 to 6.99). On the other hand, body weight reduction was significantly associated with decreases in physical activity (OR 2.63, 95% CI 1.62 to 4.27), home-cooked meals and eating between meals (OR 1.95, 95% CI 1.05 to 3.61) in the older adults.Conclusion Changes in physical activity and eating between meals were associated with body weight change under the COVID-19 pandemic among Japanese.

Purpose The purpose of this study was to evaluate sequential patellar height changes as well as the factors leading to these changes after medial open-wedge high tibial osteotomy (MOWHTO). Methods The study cohort constituted 37 knees from 36 patients who underwent MOWHTO for varus knee. The Caton–Deschamps index (CDI) for patellar height was measured preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The factors related to sequential changes in patellar height were evaluated. Results Significant differences were observed between preoperative CDI and postoperative CDI at all time points ( p < .05). Two-week postoperative CDI and postoperative CDI at 3,6,12-months was also significantly different ( p < .05). The only significant factor for the change in patellar height between preoperative CDI and postoperative CDI at 2-weeks and 12-months was the change in the Δ medial proximal tibial angle (ΔMPTA) (postoperative MPTA–preoperative MPTA). We could not identify the factor that affected the change in patellar height change from 2-weeks postoperatively. Conclusion The change in patellar height continued sequentially until at least 3 months postoperatively. ΔMPTA was associated with the change in patellar height at 2 weeks postoperatively compared with preoperatively; however, no factors associated with the change in patellar height from 2 weeks postoperatively to 3, 6, and 12-months postoperatively were identified.

Introduction: Non-fasting triglyceride (TG) concentrations are useful for predicting various diseases, but most epidemiological studies investigated the association between fasting TG concentrations and chronic kidney disease (CKD). This study aimed to examine the association between casual (fasting or non-fasting) serum TG concentrations and new-onset CKD in the general Japanese population. Methods: We conducted a population-based, retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. Between 2008 and 2019, participants without CKD (estimated glomerular filtration rate

ObjectiveThis study aimed to investigate the incidence rates and predictors of lower limb fractures in a general Japanese population.MethodsNIPPON DATA is a nationwide, long-term, prospective cohort study of individuals who participated in the National Cardiovascular Survey Japan and the National Nutrition Survey in 1990. Overall, 3,134 individuals (1,827 women, 1,307 men) who participated in follow-up assessments in 1995, 2000, and/or 2006 were included in the present analysis. The outcomes of this study were lower limb fractures (including proximal femur fractures).ResultsThe mean age at baseline was 63.8 years in women and 63.1 years in men. The average body mass index (BMI) was 23.3 kg/m2 in women and 22.9 kg/m2 in men. During a mean follow-up of 12.1 years, 271 total lower limb fractures were observed. In women, older age, lower BMI, and less intake of vegetables were associated with increased risks of proximal femur fractures. With regard to the outcome of total lower limb fractures, less intake of vegetables and regular exercise were significant predictors in women. Calcium intake was not significantly associated with proximal femur or total lower limb fractures. There were no significant predictors of proximal femur or total lower limb fractures in men, except for age.ConclusionsAging was a significant risk factor for proximal femur and total lower limb fractures in both men and women. With regard to modifiable risk factors, low BMI and low intake of vegetables were associated with increased risks of proximal femur and/or total lower limb fractures in the general population of Japanese women.

Background and Purpose Although numerous measures for stroke exist, stroke remains one of the leading causes of death in Japan. In this study, we aimed to determine the long-term survival rate after first-ever stroke using data from a large-scale population-based stroke registry study in Japan. Methods Part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based registry study of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in Japan. A total 1,880 patients with non-fatal first-ever stroke (among 29-day survivors after stroke onset) registered in 2011 were followed up until December 2016. Five-year cumulative survival rates were estimated using the Kaplan-Meier method, according to subtype of the index stroke. Cox proportional hazards models were used to assess predictors of subsequent all-cause death. Results During an average 4.3-year follow-up period, 677 patients died. The 5-year cumulative survival rate after non-fatal first-ever stroke was 65.9%. Heterogeneity was present in 5-year cumulative survival according to stroke subtype: lacunar infarction, 75.1%; large-artery infarction, 61.5%; cardioembolic infarction, 44.9%; intracerebral hemorrhage, 69.1%; and subarachnoid hemorrhage, 77.9%. Age, male sex, Japan Coma Scale score on admission, and modified Rankin Scale score before stroke onset were associated with increased mortality during the chronic phase of ischemic and hemorrhagic stroke. Conclusions In this study conducted in a real-world setting of Japan, the 5-year survival rate after non-fatal first-ever stroke remained low, particularly among patients with cardioembolic infarction and large-artery infarction in the present population-based stroke registry.

Abstract Background For acute ischemic stroke (AIS) patient receiving mechanical thrombectomy (MT), renal dysfunction was an independent risk factor of contrast-induced nephropathy which may affect clinical outcomes. However, the influence of renal function on stroke outcomes is still controversial. Thus, we aim to investigate the association between renal function and outcomes of AIS patients receiving MT. Methods All consecutive stroke patients receiving MT were included in a prospective stroke registry in China from April 2015 to February 2019. Estimated glomerular filtration rate (eGFR) was measured on admission and categorized into G1 (≥ 90 ml/min/1.73 m2), G2 (60–89 ml/min/1.73 m2), G3a (45–59 ml/min/1.73 m2) and G3b-5 (≤44 ml/min/1.73 m2). Multivariable logistic regression analysis was performed to evaluate the association between eGFR and recanalization rate (thrombolysis in cerebral infarction scale 2b-3), symptomatic intracranial hemorrhage (sICH), death in hospital, death at 3 months and poor functional outcome (modified Rankin Scale 3–6 at 3 months). Results A total of 373 patients were included in the study. Of them, 130 (34.9%) patients were in the eGFR group G1, 170 (45.6%) in G2, 46 (12.3%) in G3a, 27 (7.2%) in G3b–5. In multivariable logistic regression analysis, reduced eGFR was associated with increased risk of sICH (G3a, p = 0.016) and 3-month death (G3b–5, p = 0.025). However, no significant effects were observed between reduced eGFR and the risk of recanalization rate (p = 0.855), death in hospital (p = 0.970), and poor functional outcome (p = 0.644). Conclusions For AIS patients underwent MT, reduced eGFR was associated with increased risk of sICH and 3-month death. However, there were no appreciable effects of reduced eGFR on recanalization rate, death in hospital and 3-month functional outcome.

Background and Purpose: Hematoma volume is a key determinant of outcome in acute intracerebral hemorrhage (ICH). We aimed to compare estimates of ICH volume between simple (ABC/2, length, width, and height) and gold standard planimetric software approaches. Methods: Data are from the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Multivariable linear regression was used to compare ICH volumes on baseline CT scans using the ABC/2, modified ABC/2 (mABC/2), and MIStar software. Other aspects of ICH morphology examined included location, irregularity, heterogeneity, intraventricular and subarachnoid hemorrhage extension (SAH) of hematoma, and associated white matter lesions and brain atrophy. Results: In 2,084 patients with manual and semiautomated measurements, median (IQR) ICH volumes for each approach were: ABC/2 11.1 (5.11–20.88 mL), mABC/2 7.8 (3.88–14.11 mL), and MIStar 10.7 (5.59–18.66 mL). Median differences between ABC/2 and MIStar, and mABC/2 and MIStar were 0.34 (–1.01 to 2.96) and –2.4 (–4.95 to –0.7416), respectively. Hematoma volumes differed significantly with irregular shape (ABC/2 and MIStar, p < 0.001; mABC/2 and MIStar, p = 0.007) and larger volumes (mABC/2 and MIStar, p < 0.001; ABC/2 and MIStar, p = 0.07). ICH with SAH showed a significant discrepancy between ABC/2 and MIStar (p < 0.001). Conclusions: Overall, ABC/2 performs better than mABC/2 in estimating ICH volume. The largest discrepancies were evidenced against automated software for irregular-shaped and large ICH with SAH, but the clinical significance of this is uncertain.

Abstract:: How do people change their healthcare behavior when a public health crisis occurs? Within a year of its emergence, coronavirus disease 2019 (COVID-19) has gradually infiltrated our lives and altered our lifestyles, including our healthcare behaviors. In Japan, which faces China across the East China Sea and accepted 924,800 Chinese tourists in January 2020, the emergence and spread of COVID-19 provides a unique opportunity to study people's reactions and adaptations to a pandemic.Patients with chronic illnesses who require regular doctor visits are particularly affected by such crises. We focused on diabetic patients whose delay in routine healthcare invites life-threatening complications and examined how their patterns of doctor visits changed and how demographic, socioeconomic, and vital factors disparately affected this process. We relied on the insurance claims data of a health insurance association in Tokyo. By using panel data of diabetic patients from April 2018 to September 2020, we performed visual investigations and conditional logistic regressions controlling for all time-invariant individual characteristics.Contrary to the general notion that the change in healthcare behavior correlates with the actual spread of the pandemic, the graphical and statistical results both showed that diabetic patients started reducing their doctor visits during the early stage of the pandemic. Furthermore, a substantial decrease in doctor visits was observed in women, and large to moderate reductions were seen in patients who take insulin and are of advanced age, who are at high risk of developing severe COVID-19. By contrast, no differentiated effect was found in terms of income status. We further investigated why a change in pattern occurred for each subgroup.The patterns of routine healthcare revealed by this study can contribute to the improvement of communication with the target population, the delivery of necessary healthcare resources, and the provision of appropriate responses to future pandemics. (299 words).

Background We investigated whether blood pressure lowering for secondary prevention is associated with a reduction in recurrent stroke risk and/or a higher risk of adverse events in very elderly compared with younger trial participants. Methods and Results This is a random effects meta‐analysis of randomized controlled trials of blood pressure lowering for secondary stroke prevention to evaluate age‐stratified (

Background: Pemetrexed is a key drug in chemotherapy for nonsquamous non-small-cell lung cancer (nonsq NSCLC). Several studies have reported thyroid transcription factor-1 (TTF-1) as a biomarker of the efficacy in chemotherapy regimens, including pemetrexed in non-Asian people. Objective: We aimed to examine the impact of the results of the TTF-1 immunostaining of tumor cells on the therapeutic effect of chemotherapy in Japanese patients with nonsq NSCLC. Methods: We examined the results of TTF-1 immunostaining and the clinical background of Japanese patients with nonsq NSCLC who received platinum-doublet chemotherapy at our hospital, from April 2009 to April 2021, and the correlation between regimens with or without pemetrexed in progression-free survival (PFS) and overall survival (OS). The efficacy of each regimen was then compared between TTF-1-positive and TTF-1-negative tumors. Results: TTF-1 immunostaining was performed in 145 patients during the study period: 92 were positive, and 53 were negative. A total of 24 patients presented with EGFR/ALK gene abnormality (16.6%). The PFS and OS of patients who were TTF-1-positive tended to be longer than those of the patients who were TTF-1-negative under either regimen. In other words, patients who were TTF-1-negative were frequently resistant to numerous chemotherapy drugs and experienced a poor prognosis under both regimens. The OS of patients who were TTF-1-positive and treated with the pemetrexed regimen was significantly longer than those on regimens without pemetrexed (963 vs. 412 days, HR = 0.73; 95% CI 0.55–0.96, p = 0.022), whereas there was no difference in PFS. Conclusions: The positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who have advanced nonsq NSCLC. Our analysis examined the possibility of a pemetrexed regimen leading to a longer prognosis in Asian patients who were TTF-1-positive for nonsq NSCLC, as shown in previous studies.

Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain.Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial of thrombolysis-eligible acute ischemic stroke (AIS) patients with elevated systolic BP (SBP >150 mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP

Abstract Aims/Introduction Sodium–glucose cotransporter 2 inhibitors reduce bodyweight (BW) by creating a negative energy balance. Previous reports have suggested that this BW reduction is mainly loss of body fat and that ~20% of the reduction is lean mass. However, the effects of sodium–glucose cotransporter 2 inhibitors on BW and body composition remain unclear. We examined these effects in Japanese patients with type 2 diabetes mellitus treated with insulin. Materials and Methods In this open‐label, randomized controlled trial, 49 overweight patients (body mass index ≥23 kg/m2) with inadequate glycemic control (hemoglobin A1c >7.0%) receiving insulin treatment were randomly assigned to receive add‐on ipragliflozin or no additional treatment (control group). Patients were followed for 24 weeks. The goal for all patients was to achieve glycated hemoglobin

Background: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. Methods: From 2006–2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1–160.9, 161–321.9, 322–482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend

Abstract Background The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. Methods Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. Results Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56–6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22–0.68) and higher in men who were not working and aged

Background/Purpose: Because atherosclerotic factors and antithrombotic agents sometimes induce cerebral microbleeds (CMBs), patients with cerebral large artery disease (CLAD) tend to have more CMBs than control subjects. On the other hand, VEGF contributes to the disruption of the blood-brain barrier, and it may induce parenchymal edema and bleeding. We conducted a study to evaluate the role of vascular endothelial growth factor (VEGF) in the occurrence of CMBs in patients with CLAD. Methods: CLAD is defined as stenosis or occlusion of either the carotid artery or the middle cerebral artery of 50% or more. We prospectively registered patients with CLAD who were hospitalized in our neurocenter. Biological backgrounds, atherosclerotic risk factors, administration of antithrombotics before hospitalization, and levels of cytokines and chemokines were evaluated. Susceptibility-weighted imaging or T2*-weighted MR angiography was used to evaluate CMBs. The Brain Observer MicroBleed Scale (BOMBS) was used for CMB assessments. Images were analyzed with regard to the presence or absence of CMBs. We also examined plasma VEGF concentrations using a commercial ELISA kit. Because more than half showed plasma VEGF levels below assay detection limits (3.2 pg/mL), the patients were dichotomized by plasma VEGF levels into two groups (above and below the detection limit). After univariate analyses, logistic regression analysis was conducted to determine the factors associated with the CMBs after adjustment for age, sex, the presence of hypertension, and administration of antithrombotic agents. A similar analysis with CMBs separated by location (cortex, subcortex, or posterior circulation) was also conducted. Results: Sixty-six patients (71.1 ± 8.9 years, 53 males and 13 females) were included in this study. Plasma VEGF levels were not correlated with age, sex, and atherosclerotic risk factors; however, patients with VEGF levels >3.2 pg/mL tended toward more frequent CMBs (60.0 vs. 32.6%, in the presence and absence of CMBs, p = 0.056). With regard to the location of CMBs, those in the cortex and/or at the gray-white junction were observed more frequently in the patients with VEGF levels >3.2 pg/mL after multivariable analyses (odds ratio: 3.80; 95% confidence interval: 1.07–13.5; p = 0.039). Conclusions: In patients with CLAD, elevated plasma VEGF might be associated with CMBs, especially those located in the cortex and/or at the gray-white junction.

The aim of this study was to investigate the contribution of gene polymorphisms, in combination with habitual caffeine consumption, to the effect of caffeine intake on hemodynamic and psychoactive parameters. A double-blind, prospective study was conducted with 201 healthy volunteers randomly allocated 2:1 to the caffeinated group (150 mL decaffeinated coffee with additional 200 mg caffeine) or decaffeinated group (150 mL decaffeinated coffee). We measured the changes in blood pressure (BP) and calculation speed upon coffee intake, stratifying with gene polymorphisms, e.g., those in adenosine A2A receptor (ADORA2A) and cytochrome P450 (CYP) 1A2, and daily caffeine consumption (≤90 mg/day and >90 mg/day). Overall, caffeine intake independently increased BP and calculation speed (p-values

Constipation is one of the most common non-motor symptoms in multiple system atrophy (MSA); however, it has not been evaluated according to the standard diagnostic criteria for constipation in patients with MSA. We evaluated the characteristics of constipation in patients with MSA by using Rome criteria (Rome III), which has been validated and the widely used for gastrointestinal disorders. Fifty-one patients with MSA (29 female) were enrolled in the study. Based on the Rome III criteria, constipation was diagnosed in 29 patients (56.9%); irritable bowel syndrome was not detected. Thirty-seven patients (72.5%) were aware of their constipation. The most common constipation symptom was the sensation of anorectal obstruction (68.6%). Patients’ self-awareness of constipation was most strongly correlated to the sensation of incomplete evacuation (odds ratio: 7.377, 95% confidence interval: 1.402–38.817). The number of constipation-related symptoms was correlated with the total levodopa equivalent dose (p < 0.05). Rome criteria, which can detect various constipation symptoms, are useful for evaluating constipation in MSA, and these findings may greatly impact personalized medicine.

ObjectivesThis study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population.MethodsWe conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (ResultDuring an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009).ConclusionThe WBC count was associated with future development of hypertension in the general Japanese population.

ObjectiveThe aim of this study was to investigate prevalence of idiopathic and secondary restless legs syndrome (RLS) according to pregnancy trimester, and its effects on delivery-related outcomes among pregnant women in Japan.MethodsThis was a single-center, prospective observational study. One hundred eighty-two consecutive pregnant women participated in the study from June 2014 to March 2016. Participants were interviewed and examined in the second and third trimesters of pregnancy and 1 month after delivery. At each term, RLS was identified by a research assistant and then specialist in sleep medicine based on the diagnostic criteria of the International Restless Legs Syndrome Study Group. Delivery-related data was collected from medical charts. RLS was classified as idiopathic RLS, which originally existed before the index pregnancy, or secondary RLS, which newly appeared during the index pregnancy.ResultsThe prevalence of RLS was 4.9% (idiopathic 3.3%, secondary 1.6%) in the second trimester, 5.0% (idiopathic 0.0%, secondary 5.0%) in the third trimester, and 0.6% (idiopathic 0.0%, secondary 0.6%) after delivery. Prolonged labor, emergency Cesarean section, and arrest of labor tended to be more frequent in idiopathic and/or second RLS (all pConclusionsThe prevalence of RLS during pregnancy was 4-5% and decreases after delivery in current Japan. The presence of RLS was associated with an increase in some delivery-related outcomes. Early detection and treatment of RLS during pregnancy may be beneficial to safe delivery for pregnant women.

BackgroundDialysis-related amyloidosis (DRA) commonly develops in patients undergoing long-term dialysis and can lead to a decline in activities of daily living and quality of life (QOL), mainly owing to orthopedic complications.MethodsFirst, we determined utility scores of the EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in 1,323 patients with DRA who had undergone dialysis for more than 10 years and compared the score between those with and without DRA. Second, a 2-year follow-up was also performed, in which patients were divided into three groups: those complicated by DRA from the beginning, those with newly developed DRA within the 2-year period, and those not complicated by DRA throughout the survey period; changes in the EQ-5D-3L utility score were compared. In the group already complicated by DRA at the survey baseline, changes in the EQ-5D-3L utility score were compared according to the dialysis treatment method.ResultsA total of 1,314 and 931 patients were included in the first and second studies, respectively. EQ-5D-3L utility scores among patients diagnosed with DRA were significantly lower than scores in those not diagnosed with DRA. The reduction in the EQ-5D-3L utility score over the 2-year follow-up was significantly greater in patients newly complicated by DRA during the follow-up period after enrollment but not in those complicated by DRA from the beginning, as compared with patients not complicated by DRA throughout the survey period. The reduction in utility score tended to be lower in patients routinely treated with a β2-microglobulin adsorption column than in untreated patients with DRA.ConclusionComplication by DRA in patients undergoing long-term hemodialysis was significantly associated with a decline in QOL.

Background This large‐scale observational study on negative events in a real‐world setting investigated Japanese patients with atrial fibrillation who were not on anticoagulants. This study aims to evaluate the incidence of ischemic stroke and bleeding events (intracranial hemorrhage, gastrointestinal bleeding, others) based on CHA2DS2‐VASc scores in Japanese patients with atrial fibrillation who were not anticoagulated. Methods and Results We used health checkups and insurance claim data from a Japanese insurance organization. Altogether, 9733 atrial fibrillation patients were not prescribed anticoagulation during their follow‐up periods. Patients’ risk levels were defined by their CHA2DS2‐VASc scores (range 0–≥3): Men with scores of 0, 1, or ≥2 and women with scores of 1, 2, or ≥3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA2DS2‐VASc‐determined risk and the incidence of ischemic stroke and intracranial, gastrointestinal, and other bleeding. The mean 2.5‐year follow‐up revealed 143 ischemic strokes and 332 bleeding events. Annual event rates were 0.58% for ischemic stroke and 1.17% for total bleeding events. Annual incidence of ischemic stroke increased with elevated predicted risks based on CHA2DS2‐VASc scores: 0.18% for low‐risk, 0.44% intermediate‐risk, and 1.29% high‐risk groups (P

Abstract Introduction To examine whether sex and polymorphisms of cytochrome P450 (CYP) 2B6 and UDP-glucuronosyltransferase (UGT) 1A9 affect the difference between predicted and measured plasma propofol concentration during continuous infusion by target-controlled infusion. Results Blood samples of 69 patients (48 men and 21 women) were obtained at 4 h after initial propofol infusion. Percentage performance error (PE) was calculated to assess the difference between measured and predicted propofol concentration. Regression coefficients (β) and 95% confidence intervals (CI) of sex and the polymorphisms of CYP2B6 and UGT1A9 for PE were, separately and mutually, estimated with linear regression. Covariates included age and body mass index in the minimal adjusted model, and additionally included clinical factors (mean blood pressure, heart rate, volume of intravenous fluid, surgical site, surgical position, and pneumoperitoneum) in the full adjusted model. PE was higher in men than in women (28.7% versus 10.5%, p = 0.015). Female sex was inversely associated with PE: the minimal adjusted β = − 8.84 (95% CI, − 16.26 to − 1.43); however, the fully adjusted β with clinical factors became not significant. The average of PE did not differ between polymorphisms of CYP2B6 and UGT1A9, and β of CYP2B6 516G>T polymorphisms mutually adjusted with female sex was not significant. Mean blood pressure, heart rate, and volume of intravenous fluid were independently associated with PE in the full adjusted model. Conclusions Under 4 h anesthesia with propofol target-controlled infusion in our population, sex differences appeared to exist in the propofol concentration, which might be largely mediated by clinical factors, such as hemodynamic status. Trial registration UMIN-CTR UMIN000009015, Registered 1 October 2012

Background: Obstructive sleep apnoea (OSA) is a common comorbidity in patients with cardiovascular (CV) disease. We aimed to identify specific OSA clinical phenotypes relating to risks of serious CV events and response to continuous positive airway pressure (CPAP) treatment. Methods: Post-hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) study in participants with moderate-to-severe OSA and coronary artery disease (CAD) and/or cerebrovascular disease (CeVD) randomised to CPAP plus usual care or usual care alone. Latent class analysis (LCA) was used to identify OSA clinical phenotypes among 2649 (out of 2687 total) patients with complete data on 19 patient-centered variables, supported by Bayesian information criteria and clinical interpretability. Cox regression models were used to evaluate risks of composite cardiac and stroke outcome events in phenotype groups. Preferential response to CPAP treatment was evaluated using interaction terms as well as the Chi-square test. Findings: LCA identified four OSA clinical phenotypes: CAD alone and with diabetes mellitus (CAD+DM), and CeVD alone and with DM (CeVD+DM), in 39%, 15%, 37% and 9% of participants, respectively. The rates of composite CV events were the highest in CAD+DM phenotype (HR 2.08, 95% CI 1.57–2.76) and for stroke were highest in CeVD+DM phenotype (HR 6.84, 95% CI 3.77–12.42). Adherence to CPAP treatment (nil or

Background/Aims: Angiotensin receptor blockers (ARBs) may be beneficial for clinical remission during conventional therapy with tonsillectomy and steroid pulse (TSP) for active IgA nephropathy. Methods: Seventy-seven patients with active IgA nephropathy were randomly assigned to the control arm with conventional regimen (TSP followed by oral prednisolone) (n = 37) or the ARB arm with conventional regimen plus ARB candesartan for the first 6 months (n = 40). Patients not achieving proteinuria remission at 12 months in either arm were administered candesartan, which was titrated until the 24-month follow-up. The primary endpoints were remission of proteinuria (< 0.3 g/gCr) and hematuria at 12 months. Results: Baseline proteinuria (g/g Cr) were comparable between the control and ARB arm (1.02 vs. 0.97, P = 0.97). Similarly, cumulative remission rates at 6, 12, and 24 months were comparable between the control and ARB arms (37.8% vs. 35% [P = 0.80], 48.7% vs. 38.5% [P = 0.37], 71.4% vs. 51.3% [P = 0.08]). Proteinuria, which was slightly worse in the control arm than in the ARB arm at 6 months, was comparable afterwards (0.20 vs. 0.23 g/g Cr at 12 months; 0.12 vs. 0.13 g/g Cr at 24 months). Significant reductions observed in urinary angiotensinogen were almost comparable between the two treatment arms at both 6 and 12 months. Conclusion: Early candesartan treatment combined with TSP may not benefit clinical remission regardless of the blood pressure. ARB titration later during the treatment might provide benefit for patients with active IgA nephropathy.

Background: Reducing the urinary sodium-to-potassium ratio is important for reducing both blood pressure and risk of cardiovascular disease. Among free-living Japanese individuals, we carried out a randomized trial to clarify the effect of lifestyle modification for lowering urinary sodium-to-potassium ratio using a self-monitoring device. Methods: This was an open, prospective, parallel randomized, controlled trial. Ninety-two individuals were recruited from Japanese volunteers. Participants were randomly allocated into intervention and control groups. A month-long dietary intervention on self-monitoring urinary sodium-to-potassium ratio was carried out using monitors (HEU-001F, OMRON Healthcare Co., Ltd., Kyoto, Japan). All participants had brief dietary education and received a leaflet as usual care. Monitors were handed out to the intervention group, but not to the control group. The intervention group was asked to measure at least one spot urine sodium-to-potassium ratio daily, and advised to lower their sodium-to-potassium ratio toward the target of less than 1. Outcomes included changes in 24-hour urinary sodium-to-potassium ratio, sodium excretion, potassium excretion, blood pressure, and body weight in both groups. Results: Mean measurement frequency of monitoring was 2.8 times/day during the intervention. Changes in urinary sodium-to-potassium ratio were −0.55 in the intervention group and −0.06 in the control group (P = 0.088); respective sodium excretion changes were −18.5 mmol/24 hours and −8.7 mmol/24 hours (P = 0.528); and corresponding potassium excretion was 2.6 mmol/24 hours and −1.5 mmol/24 hours (P = 0.300). No significant reductions were observed in either blood pressure or body weight after the intervention. Conclusions: Providing the device to self-monitor a sodium-to-potassium ratio did not achieve the targeted reduction of the ratio in “pure self-management” settings, indicating further needs to study an effective method to enhance the synergetic effect of dietary programs and self-monitoring practice to achieve the reduction. However, we cannot deny the possibility of reducing sodium-to-potassium ratio using a self-monitoring device.

Abstract Door-to-needle time (DNT) is a key performance indicator for efficient use of intravenous thrombolysis in acute ischemic stroke (AIS). We aimed to determine whether DNT improved over time in the Enhanced Control of Hypertension and Acute Stroke Study (ENCHANTED) and the clinical predictors of DNT. Temporal trends in DNT were assessed across fourths of time since activation of study centers using generalized linear model. Predictors of long DNT (>60 min) were determined in logistic regression models. Overall mean DNT (min) was 71.8 (95% confidence interval [CI] 70.4–73.2), but decreased significantly over time (fourths): 77.9 (74.9–80.9), 69.3 (66.7–72.0), 69.1 (66.5–71.8) and 71.4 (68.7–74.2) (P for trend, 0.003). The reduction in DNT was particularly marked in China (P for trend, 0.001), but was not significant across the other participating countries (P for trend, 0.065). Independent predictors of long DNT were recruitment from China, short onset-to-door time, lower numbers of patients treated per center, higher diastolic blood pressure, off-hour admission, and absence of proximal clot occlusion. DNT in ENCHANTED declined progressively during the trial, especially in China. However, DNT in China is still longer than the key performance parameter of ≤60 minutes recommended in guidelines. Effective national programs are needed to improve DNT in China.