Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies.

BACKGROUND: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown. METHODS: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database. RESULTS: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database. CONCLUSIONS: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079.

Influence of Time to Achieve Target Systolic Blood Pressure on Outcome After Intracerebral Hemorrhage: The Blood Pressure in Acute Stroke Collaboration.

OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage. METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect. RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events. CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

The gut microbiota and coronary artery calcification in Japanese men.

BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into 4 groups based on their CAC scores: CAC = 0, 0

Predictors of Early versus Delayed Neurological Deterioration after Thrombolysis for Ischemic Stroke.

INTRODUCTION: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death). RESULTS: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). CONCLUSION: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Statistical Analysis Plan for the INTEnsive Ambulance-Delivered Blood Pressure Reduction in Hyper-ACute Stroke Trial.

INTRODUCTION: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4), a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of prehospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock. METHODS: Patients were randomized (1:1) to intensive (target systolic BP 130-140 mm Hg within 30 min) or guideline-recommended BP management (BP lowering only considered if systolic BP >220 mm Hg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2,320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic. CONCLUSION: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis and to avoid potential bias in the evaluation of the trial intervention.

Intensive blood pressure lowering and renal function in ischemic stroke patients: secondary analysis of ENCHANTED trial.

BACKGROUND: Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is early change in renal function, defined by a difference in estimated glomerular filtration rate (∆eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation [SD]) and magnitude of reduction within 24 h. RESULTS: Of 2151 participants (mean age 66.9 years; 38% female) included with available baseline eGFR, there were significant differences in attained 144.3±10.2 vs 149.8±12.0 [5.5 mm Hg]; P<0.0001), variation (15.1±5.4 vs 14.0±5.6 mm Hg; P<0.0001) and magnitude of reduction (44.6±16.2 vs 38.7±17.6 mm Hg; P<0.0001) in SBP within 24 hours. 1718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in ∆eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; P=0.29) between the intensive and guideline groups, respectively. The neutral effect on ∆eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputation for missing follow-up eGFR. SBP variability was significantly associated with decreasing ∆eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95%CI -2.43 to -0.28; P for trend=0.01). CONCLUSIONS: Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR. CLINICAL TRIAL REGISTRATION: ENCHANTED is registered at ClinicalTrials.gov (NCT01422616).

Improvement of medication adherence for desmopressin by adjusting the prescription dosage in male patients with overactive bladder: A claims database analysis.

OBJECTIVES: Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence. METHODS: Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan-Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin. RESULTS: The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high-adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC. CONCLUSION: Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.

Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

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 <60 mL/min/1.73 m2 and/or proteinuria) at baseline. Breakfast skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the estimated glomerular filtration rate (eGFR) from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. RESULTS: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p = 0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI: 1.29-5.26) for the breakfast-skipping group (p = 0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR, and baseline proteinuria. CONCLUSION: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Effect of Pharmacotherapy for Overactive Bladder on the Incidence of and Factors Related to Urinary Tract Infection: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection. MATERIALS AND METHODS: A comprehensive search was performed in MEDLINE and the Cochrane Library using terms for overactive bladder, antimuscarinic agents, and beta 3-adrenoceptor agonists. The primary end point was the emergence of urinary tract infection after pharmacotherapy for overactive bladder. The secondary end point was the emergence of urinary retention, dysuria, and/or increased residual urine volume after overactive bladder treatment. Meta-analyses were conducted using random-effects models. RESULTS: A total of 35,939 patients in 33 trials (29 trials of antimuscarinic agents vs placebo, and 9 trials of beta 3-adrenoceptor agonists vs placebo) that included patients with overactive bladder were identified. At 1-3 months after treatment, the incidence of urinary tract infections was statistically significantly higher in the patients treated with antimuscarinic agents (RR: 1.23, 95% CI: 1.04, 1.45; P = .013) than in the placebo control group. The incidence of urinary tract infections was not increased in the patients treated with beta 3-adrenoceptor agonists (RR: 1.04, 95% CI: 0.76, 1.42; P = .796). Antimuscarinic agents also statistically significantly increased the risks of urinary retention, dysuria, and/or increased residual urine volume (RR: 2.88, 95% CI: 1.79, 4.63; P < .001), whereas beta 3-adrenoceptor agonists did not (RR: 1.26, 95% CI: 0.38, 4.14; P = .708). CONCLUSIONS: This meta-analysis showed that antimuscarinic agents statistically significantly increased the incidences of urinary tract infection and lower urinary tract symptoms and dysfunction, but beta 3-adrenoceptor agonists did not. To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents.

Early Enhancement with Contrast-Enhanced Ultrasonography Relates to the Number of Small-Diameter Neovessels in the Carotid Plaque.

BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) have been recognized as a major cause of intraplaque hemorrhage and subsequent vulnerability of the carotid plaque. However, the exact mechanisms by which INVs cause intraplaque hemorrhage remain unclear. Various sizes of INVs coexist in carotid plaques pathologically, and we hypothesized that the size of INVs would be associated with carotid plaque histology, particularly in terms of intraplaque hemorrhage. Detection method of INV is important when determining whether carotid plaques are vulnerable, and contrast-enhanced ultrasonography (CEUS) is one of the most useful methods to detect them. The purpose of this study was to examine the relationship between findings from CEUS and vascular pathology obtained by carotid endarterectomy (CEA). We focused on associations between small and large INVs evaluated by CEUS and histologically defined intraplaque hemorrhage. METHODS: Participants comprised 115 patients (mean age, 73.0 ± 7.2 years; 96 men) who underwent preoperative CEUS and underwent CEA. CEUS findings were evaluated as vascular grade at 0 min (Vas-G0) and 10 min (Vas-G10) after contrast injection. Plaques were histologically evaluated quantitatively for the total area of intraplaque hemorrhage, cholesterol, and calcification and the thinnest fibrous cap. Immunohistochemical studies were conducted using anti-CD-34 antibody as a marker for endothelial cells. INVs were divided into two groups depending on diameter: small INVs, <50 µm; and large INVs, ≥50 µm. The numbers of small and large blood vessels in the plaque were quantified histologically. Associations of small and large INVs with CEUS, plaque histology, and clinical findings were assessed by uni- and multivariable analyses. RESULTS: Multivariable analyses indicated that CEUS Vas-G0 was associated with the 4th quartile of the number of small INVs compared with other quartiles, and Vas-G10 was associated with the 4th quartile of the number of large INVs. Histologically, the presence and area of intraplaque hemorrhage were associated with the number of small INVs, while the increased number of large INVs was associated with infrequent plaque disruption and thicker fibrous cap. CONCLUSIONS: Our study showed that early phase enhancement in the CEUS can help identify plaque vulnerability by predicting a larger number of small INVs. This information can also help determine treatment strategies for carotid plaque.

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients: The Shiga Stroke and Heart Attack Registry.

BACKGROUND: The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke. METHODS: A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset. RESULTS: A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients. CONCLUSIONS: The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study.

INTRODUCTION: The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. METHODS: For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2-6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer's perspective. The equivalence margin for cost and effectiveness was set at USD 691 and -0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. RESULTS: While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: -1,000-1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415-509) and 410 (95% CI: 363-457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: -0.016-0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. CONCLUSIONS: This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.

Casual Serum Triglyceride Concentrations and New-Onset Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease Study.

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 checkup data of residents of Iki City, Nagasaki Prefecture, Japan. Between 2008 and 2019, participants without CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or proteinuria) at baseline were included. Casual serum TG concentrations were classified by sex as tertile 1 (men: <0.95 mmol/L; women: <0.86 mmol/L), tertile 2 (0.95-1.49 mmol/L; 0.86-1.25 mmol/L), and tertile 3 (≥1.50 mmol/L; ≥1.26 mmol/L). The outcome was incident CKD. Multivariable-adjusted hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model. RESULTS: 4,946 participants (2,236 [45%] men and 2,710 [55%] women; 3,666 [74%] fasting and 1,182 [24%] non-fasting) were included in the present analysis. During an average follow-up of 5.2 years, 934 participants (434 men and 509 women) developed CKD. In men, the incidence rate (per 1,000 person-years) of CKD increased with an elevation in TG concentrations (tertile 1: 29.4, tertile 2: 42.2, and tertile 3: 43.3). This association was significant, even after adjustment for other risk factors of age, current smoking habits, current alcohol intake, exercise habits, obesity, hypertension, diabetes mellitus, hyper-low-density-lipoprotein cholesterolemia, and use of lipid-lowering therapy (p = 0.003 for trend). In contrast, in women, TG concentrations were not associated with incident CKD (p = 0.547 for trend). CONCLUSION: Casual serum TG concentrations are significantly associated with new-onset CKD in Japanese men in the general population.

Real-World Evidence for Risk Factors of Bruises and Fractures from Falls in Patients with Overactive Bladder: A Medical Record Analysis.

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.

Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study.

BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

OBJECTIVE: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect. RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth. INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent. PROSPERO REGISTRATION NUMBER: CRD42019141136.

The 21-Year Trend of Stroke Incidence in a General Japanese Population: Results from the Takashima Stroke Registry, 1990-2010.

INTRODUCTION: Since the 1960s, the stroke morality rate in Japan has declined significantly. Although several risk factors for stroke have become more evident due to increasingly Westernized lifestyle, there have been no population-based registry data on recent time trends in stroke incidence in Japan. The purpose of this study is to determine these trends in stroke incidence using a population-based registry. METHODS: Data were obtained from the Takashima Stroke Registry, which covers approximately 50,000 residents in Takashima City, Japan. The age- and sex-standardized stroke incidence rate was estimated using the direct method. Average annual relative changes of stroke incidence were estimated using Poisson regression models. RESULTS: We identified a total of 2,371 patients with first-ever stroke during the period 1990-2010. Crude incidence rates of total stroke (per 100,000 person-years) were 225 in the early period (1990-2001) and 187 in the late period (2002-2010), and the mean age at onset of stroke increased from 71.9 years in the early period to 74.8 years in the late period. Age- and sex-standardized incidence rates of stroke (per 100,000 person-years) decreased from 327 in the early part of this study period and 206 in the later period. During the 21-year period, age- and sex-standardized average annual relative reduction in stroke incidence was statistically significant (-3.7% per year). When stratified into early and late periods, the adjusted annual relative reduction in stroke incidence was observed during the early period (-2.1% per year), and there were no significant changes during the late period. CONCLUSIONS: In this population-based registry, there was a significant reduction in incidence of stroke from 1990 to 2010. Although the speed of reduction in stroke incidence appears to have slowed down after 2000, continuous public health measures are required to provide further protection against stroke.

Seasonal Variation in Incidence of Stroke in a General Population of 1.4 Million Japanese: The Shiga Stroke Registry.

INTRODUCTION: The purpose of this study was to investigate seasonal variation in stroke incidence using data from a large-scale stroke registry of general population in current Japan. METHODS: Shiga Stroke Registry (SSR) is an ongoing population-based registry of stroke that occurred in the Shiga Prefecture in central Honshu, Japan. A total 6,688 cases of first-ever stroke, with onset dates ranging from 1 January 2011 to 31 December in 2013 were included in this study. Incidence rates of first-ever stroke in each season were estimated using the person-year approach and adjusted for age and sex using the Poisson regression models. RESULTS: From 2011 to 2013, we identified a total of 6,688 stroke cases (3,570 men, 3,118 women), of which 4,480 cases had ischemic stroke (2,518 men, 1,962 women), 1,588 had intracerebral hemorrhage (857 men, 731 women) and 563 had subarachnoid hemorrhage (166 men, 397 women). Age- and sex-adjusted incidence rates of total stroke were 151 (95% confidence interval [CI] 144-160, p = <0.001 vs. summer) in spring, 130 (95% CI 122-137) in summer, 141 (95% CI 133-149, p = 0.020 vs. summer) in autumn and 170 (95% CI 161-179, p = <0.001 vs. summer) in winter. Seasonal variation was more pronounced in intracerebral hemorrhage than in ischemic stroke. CONCLUSION: In the present large-scale stroke registry of general population, incidence rates of stroke were highest in winter and lowest in summer in current Japan.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men.

BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 µmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

Effects of intensive blood pressure control on cardiovascular and cognitive outcomes in patients with atrial fibrillation: insights from the SPRINT trial.

AIMS: Patients with atrial fibrillation (AF) have an increased risk of cardiovascular events and dementia, even if anticoagulated. Hypertension is highly prevalent in AF population; however, the optimal blood pressure (BP) target for AF patients remains unknown. METHODS AND RESULTS: We conducted subgroup analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) to examine whether AF modified the treatment effects of intensive BP control on cardiovascular and cognitive outcomes using Cox proportional hazards regression and likelihood ratio tests. Among 9361 randomized participants, 778 (8.3%) had baseline AF, and 695 (89.3%) completed at least one follow-up cognitive assessment. Intensive BP control reduced the similar relative risk of cardiovascular events irrespective of the presence of AF, with all interaction P-values > 0.05. Patients with AF experienced a greater absolute risk reduction in the composite primary cardiovascular outcome (12.3 vs. 5.6 events per 1000 person-years) with intensive treatment, compared with those without AF. However, intensive BP control increased the risk of probable dementia in patients with AF [hazard ratio (HR), 2.22; 95% confidence interval (CI), 1.03-4.80], while reducing the dementia risk in patients without AF (HR, 0.75; 95% CI, 0.60-0.95; P = 0.009 for interaction). There were no significant interactions between the presence of AF and intensive BP treatment for mild cognitive impairment. CONCLUSION: Patients with AF experienced greater absolute cardiovascular benefits with intensive BP treatment, but may need to be cautious of an increased risk of dementia. This post hoc analysis should be considered as hypothesis generating and merit further study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.