Early caffeine therapy on the prevention of severe hyperkalemia in preterm infants.

BACKGROUND: The aim of this study was to evaluate the effect of caffeine therapy in preventing severe hyperkalemia in preterm infants. METHODS: We performed a single-center, retrospective study of preterm infants of 25-29 weeks' gestation admitted in our neonatal intensive care unit from January 2019-August 2020. We divided the infants into two groups: the control group (January 2019-November 2019) and the early caffeine group (December 2019-August 2020). RESULTS: We identified 33 infants (early caffeine, 15; control, 18). Baseline potassium levels were 5.3 and 4.8 mEq/L, respectively (p = 0.274). Severe hyperkalemia (K > 6.5 mEq/L) was observed in 0 (0%) and 7 (39%) (p = 0.009), in the early caffeine group and control group. The linear mixed-effect model confirmed the correlation between caffeine therapy and time from birth for the prediction of potassium levels (p < 0.001). While the potassium levels increased from baseline potassium levels at birth by 0.869 mEq/L at 12 h of birth, 0.884 mEq/L at 18 h of birth, and 0.641 mEq/L at 24 h of birth in the control group, the potassium levels were similar to the baseline levels at 12, 18, and 24 h of life in the early caffeine group. Among the clinical features, only early caffeine therapy was negatively associated with the incidence of hyperkalemia within 72 h of life. CONCLUSION: Early caffeine therapy within a few hours of life effectively prevents the incidence of severe hyperkalemia within the first 72 h of life in preterm infants of 25-29 weeks' gestation. Prophylactic early caffeine therapy can, therefore, be considered in high-risk, preterm infants.

Clinical significance of microvessels detected by in vivo optical coherence tomography within human atherosclerotic coronary arterial intima: a study with multimodality intravascular imagings.

The significance of microvessels within atherosclerotic plaques is not yet fully clarified. Associated with plaque vulnerability. The aim of this study is to examine tissue characteristics of plaque with microvessels detected by optical coherence tomography (OCT) by use of a commercially available color-coded intravascular ultrasound (IVUS) and coronary angioscopy (CAS). The subjects examined comprised of 44 patients with stable angina pectoris who underwent percutaneous coronary intervention. Microvessels were defined as a tiny tubule with a diameter of 50-300 µm detected over three or more frames in OCT. We compared the total volume of microvessels with tissue component such as fibrotic, lipidic, necrotic, and calcified volume and the number of yellow plaque. In IVUS analysis, % necrotic volume and % lipidic volume were significantly correlated and % fibrotic volume was inversely significantly correlated with the total volume of microvessel (r = 0.485, p = 0.0009; r = 0.401, p = 0.007; r = - 0.432, p = 0.003, respectively). The number of plaque with an angioscopic yellow grade of two or more was significantly correlated with the total volume of microvessel (r = 0.461, p = 0.002). The greater the luminal volume of microvessels, the more the percent content of necrotic/lipidic tissue volume within plaque and the more the number of yellow plaques. These data suggested that microvessels within coronary plaque might be related to plaque vulnerability.

Validation of the Japanese Transition Readiness Assessment Questionnaire.

BACKGROUND: For patients with childhood-onset chronic illnesses, the transition to adult care requires an understanding of transition readiness and the effectiveness of evaluation methods. However, no such psychometrically verified scales exist in Japan. This study aimed to develop a Japanese version of the Transition Readiness Assessment Questionnaire (TRAQ) and verify its validity and reliability. METHODS: The Japanese TRAQ was developed in accordance with international guidelines, followed by a preliminary survey to verify face validity among six participants who fulfilled the inclusion criteria. For the main survey 107 patients who fulfilled the same inclusion criteria were asked to complete the questionnaire and provide basic information. After descriptive statistics analysis, the construct validity of the Japanese TRAQ was tested using the t-test and Pearson's correlation coefficients. Cronbach's alpha coefficients were calculated to assess reliability. RESULTS: In the main survey, 76 participants with no missing data were included in the complete data analysis (40 males 36 females; mean age, 17.8 and 18.2 years, respectively). The mean total Japanese TRAQ score was 3.9. Cronbach's alpha coefficients were 0.94 overall and 0.8-0.96 for each of the four domains. The known-groups analysis revealed that older participants (r = 0.23, P = 0.044), those having knowledge of the disease name (yes [4.0] vs no [3.4]; P < 0.001), and making unaccompanied hospital visits (with parent/others [3.7] vs alone [4.4]; P < 0.001) had significantly higher total TRAQ scores. CONCLUSION: We confirmed preliminarily the validity and reliability of the Japanese TRAQ.

Effect of drug-coated balloon angioplasty on in-stent restenotic coronary lesions analyzed with optical coherence tomography and serial coronary artery angioscopy.

Drug-coated balloon angioplasty (DCBA) has been recognized for its utility in preventing in-stent re-restenosis (ISR); however, imaging of the neointima immediately after treatment and during follow-up has only been described in a few case reports. This study aimed to determine the efficacy and mechanism of the DCBA using imaging studies both immediately after the DCBA and during the follow-up period. We enrolled 15 consecutive patients who underwent DCBA for in-stent restenosis (ISR). The in-stent neointimal volume was evaluated using optical coherence tomography (OCT), and the in-stent yellow grade was assessed using coronary angioscopy (CAS) immediately after DCBA and during the median follow-up period of 9 (8-15) months. The neointimal volume was significantly reduced from 77.1 ± 36.2 mm3 at baseline to 60.2 ± 23.9 mm3 immediately after DCBA (p = 0.0012 vs. baseline) and to 46.7 ± 21.9 mm3 during the follow-up (p = 0.0002 vs. post DCBA). The yellow grade of the residual plaques at the ISR lesion, which indicated plaque vulnerability, was significantly decreased in the follow-up CAG (from baseline: 1.79 ± 1.03, during the follow-up: 0.76 ± 0.82; p < 0.0001). These data suggest that DCBA may inhibit neointimal formation and provide angioscopic intimal stabilization for ISR lesions.

Oral anticoagulant use and clinical outcomes in elderly Japanese patients: findings from the SAKURA AF Registry.

Direct-acting oral anticoagulants (DOACs) are widely used in aged Japanese patients with atrial fibrillation (AF), but outcome data for such patients are limited. We compared outcomes between 1895 (58.5%) patients aged < 75 years (non-elderly), 1078 (33.3%) 75-84 years (elderly) and 264 (8.2%) ≥ 85 years (very elderly) enrolled in a prospective multicenter registry. Kaplan-Meier analysis (median follow-up: 39.3 months) revealed a significantly high incidence of stroke/systemic embolism (SE) among the very elderly relative to that among the non-elderly or elderly (3.2 vs. 1.2 and 1.5 events per 100 patient-years, p < 0.001). Major bleeding in the non-elderly group was significantly infrequent relative to that among the elderly or very elderly group (1.1 vs. 1.6 vs. 1.8 events, p = 0.033). After multivariate adjustment, the stroke/SE incidence was comparable between DOAC and warfarin users, regardless of age, but major bleeding decreased significantly among very elderly DOAC users (adjusted HR 0.220, 95% CI 0.042-0.920). The greater increasing incidence of stroke/SE than major bleeding as patients age suggests that stroke prevention should outweigh the bleeding risk when anticoagulants are being considered for aged patients. Our data indicated that DOACs can be a therapeutic option for stroke prevention in very elderly patients.

Assessing archetypes of organizational culture based on the Competing Values Framework: the experimental use of the framework in Japanese neonatal intensive care units.

OBJECTIVE: To assess organizational culture in neonatal intensive care units (NICUs) in Japan. DESIGN: Cross-sectional survey of organizational culture. SETTING: Forty NICUs across Japan. PARTICIPANTS: Physicians and nurses who worked in NICUs (n = 2006). MAIN OUTCOME MEASURES: The Competing Values Framework (CVF) was used to assess the organizational culture of the study population. The 20-item CVF was divided into four culture archetypes: Group, Developmental, Hierarchical and Rational. We calculated geometric means (gmean) and 95% bootstrap confidence intervals of the individual dimensions by unit and occupation. The median number of staff, beds, physicians' work hours and work engagement were also calculated to examine the differences by culture archetypes. RESULTS: Group (gmean = 34.6) and Hierarchical (gmean = 31.7) culture archetypes were higher than Developmental (gmean = 16.3) and Rational (gmean = 17.4) among physicians as a whole. Hierarchical (gmean = 36.3) was the highest followed by Group (gmean = 25.8), Developmental (gmean = 16.3) and Rational (gmean = 21.7) among nurses as a whole. Units with dominant Hierarchical culture had a slightly higher number of physicians (median = 7) than dominant Group culture (median = 6). Units with dominant Group culture had a higher number of beds (median = 12) than dominant Hierarchical culture (median = 9) among physicians. Nurses from units with a dominant Group culture (median = 2.8) had slightly higher work engagement compared with those in units with a dominant Hierarchical culture (median = 2.6). CONCLUSIONS: Our findings revealed that organizational culture in NICUs varies depending on occupation and group size. Group and Hierarchical cultures predominated in Japanese NICUs. Assessing organizational culture will provide insights into the perceptions of unit values to improve quality of care.

Impact of coronary plaque burden and composition on periprocedural myocardial infarction and coronary flow reserve after percutaneous coronary intervention.

Periprocedural myocardial infarction (PMI) is one of the major complications of percutaneous coronary intervention (PCI). We investigated the influence of coronary plaque burden and characteristics on PMI using intravascular ultrasound (IVUS) with radiofrequency-based tissue characterization technology (iMAP). The study population consisted of 33 consecutive patients with stable angina pectoris who underwent PCI. IVUS images were recorded before and after PCI for offline analysis, and coronary flow reserve (CFR) was measured after PCI. PMI was defined as a post-PCI cardiac troponin T elevation > 5 × 99(th) percentile of the upper reference limit (0.014 ng/mL). Plaque volume in patients with PMI (n = 12) was significantly greater than that in patients without PMI (n = 21) (240.4 ± 106.0 mm(3) versus 152.1 ± 76.9 mm(3), P = 0.0096). The iMAP-IVUS analysis demonstrated that the fibrotic, lipidic, and necrotic tissue volume within culprit lesions were also greater in patients with PMI than in patients without PMI (129.4 ± 52.2 mm(3) versus 94.6 ± 40.8 mm(3), P = 0.041; 26.8 ± 10.5 mm(3) versus 15.8 ± 11.5 mm(3), P = 0.011; and 81.3 ± 48.4 mm(3) versus 40.2 ± 33.6 mm(3), P = 0.0071, respectively). Multivariate logistic analysis demonstrated that necrotic tissue volume was the only independent predictor of PMI. Multiple regression analysis demonstrated that the post-PCI CFR values signifi cantly correlated with percent plaque burden, and there were no correlations with the percent tissue burden of each plaque component. In conclusion, the iMAP-IVUS analyses demonstrate that necrotic tissue volume is a potent predictor of PMI. Microcirculatory disturbance after PCI is significantly influenced by percent plaque burden, regardless of plaque compositions.

Impact of comprehensive quality improvement program on outcomes in very-low-birth-weight infants: A cluster-randomized controlled trial in Japan.

BACKGROUND: Differences in outcomes among neonatal intensive care units (NICUs) in Japan have been noted, prompting the need for quality improvement. AIM: To assess a comprehensive quality improvement program on outcomes in very-low-birth-weight (VLBW) infants. STUDY DESIGN: A cluster-randomized clinical trial. SUBJECTS: Forty hospitals and VLBW infants born in 2012-2014 and admitted to those hospitals were study subjects. OUTCOME MEASURES: The intervention group (IG) received a comprehensive quality improvement program involving clinical practice guidelines, educational outreach visits, workshops, opinion leader training, audits, and feedback. The control group (CG) was provided only with the guidelines. The primary outcome was survival without neurological impairment at three years of age. RESULTS: IG consisted of 19 hospitals and 1735 infants, while CG included 21 hospitals and 1700 infants. There were no significant differences in gestational weeks, 29.1(26.9-31.3) vs. 29.1(26.7-31.1) or birth weights (g), 1054(789-1298) vs. 1084(810-1309) between the two groups. Both groups showed survival rates without neurological impairment of 67.2 % (1166) and 66.9 % (1137), respectively, without a significant difference. There was no significant difference in mortalities at NICU discharge between the groups, with rates of 4.0 % (70) and 4.2 % (72) respectively. Several clinically relevant improvements were observed in IG, including reduced rates of sepsis, adrenal insufficiency, transfusion for anemia, and a shorter interval to achieve full enteral feeding. However, these did not lead to improvements in the primary outcome. CONCLUSION: The comprehensive quality improvement program to Japanese NICUs did not result in a significant improvement in survival without neurological impairment in VLBW infants.

12q14 microdeletion syndrome and short stature with or without relative macrocephaly.

Patients with 12q14 microdeletion can present with short stature with or without relative macrocephaly. When associated with relative macrocephaly, the phenotype resembles Silver-Russell syndrome (SRS). Short stature is attributable to haploinsufficiency of HMGA2, but a patient with a deletion at the HMGA2 locus only did not have macrocephaly. Hence, the presence of a separate locus for a relative macrocephaly phenotype was suggested. Herein, we present a girl with a 12q14 microdeletion involving the HMGA2 locus who had short stature but did not have macrocephaly. Inclusion and exclusion mappings based on a quantitative review of the degree of relative macrocephaly and the extent of the deletions in previously reported patients with a 12q14 microdeletion demonstrated a presumptive interval for relative macrocephaly spanning a few megabases. These results confirm that a deletion spanning both HMGA2 and this presumptive interval locus would cause an SRS-like phenotype.

Clinical Importance of the LDL-C/Apolipoprotein B Ratio for Neointimal Formation after Everolimus-Eluting Stent Implantations.

AIMS: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. METHODS: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B ＞1.2 group (high LDL-C/Apo B group, n=47). RESULTS: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group. CONCLUSIONS: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.

Three-Dimensional Fluid Dynamical Features of Coronary Plaque Rupture Provoking Acute Coronary Syndrome.

AIM: Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease. METHODS: In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis. RESULTS: There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR ( p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018). CONCLUSIONS: Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

Low alanine aminotransferase levels are independently associated with mortality risk in patients with atrial fibrillation.

Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 < ALT < 23 U/L, n = 1055), and third (ALT ≥ 23 U/L, n = 1003). The first tertile had an older age; lower body mass index (BMI); higher prevalence of heart failure; and lower hemoglobin, total cholesterol, and triglycerides (all P < 0.05). During median 39.2 months follow-up, the first tertile had significantly higher incidences of cardiovascular and all-cause mortality (log-rank P < 0.001). Lower ALT was significantly associated with the incidence of cardiovascular and all-cause mortality, even after adjusting for clinically relevant factors (P < 0.05). Low ALT may reflect aging, sarcopenia, and malnutrition and be independently associated with a high risk of all-cause mortality in patients with AF.

High Wall Shear Stress Is Related to Atherosclerotic Plaque Rupture in the Aortic Arch of Patients with Cardiovascular Disease: A Study with Computational Fluid Dynamics Model and Non-Obstructive General Angioscopy.

AIMS: Wall shear stress (WSS) has been considered a major determinant of aortic atherosclerosis. Recently, non-obstructive general angioscopy (NOGA) was developed to visualize various atherosclerotic pathologies, including in vivo ruptured plaque (RP) in the aorta. However, the relationship between aortic RP and WSS distribution within the aortic wall is unclear. This study aimed to investigate the relationship between aortic NOGA-derived RP and the stereographic distribution of WSS by computational fluid dynamics (CFD) modeling using three-dimensional computed tomography (3D-CT) angiography. METHODS: We investigated 45 consecutive patients who underwent 3D-CT before coronary angiography and NOGA during coronary angiography. WSS in the aortic arch was measured by CFD analysis based on the finite element method using uniform inlet and outlet flow conditions. Aortic RP was detected by NOGA. RESULTS: Patients with a distinct RP showed a significantly higher maximum WSS value in the aortic arch than those without aortic RP (56.2±30.6 Pa vs 36.2±19.8 Pa, p=0.017), no significant difference was noted in the mean WSS between those with and without aortic RP. In a multivariate logistic regression analysis, the presence of a maximum WSS value more than a specific value was a significant predictor of aortic RP (odds ratio 7.21, 95% confidence interval 1.78-37.1,p=0.005). CONCLUSIONS: Aortic RP detected by NOGA was strongly associated with a higher maximum WSS in the aortic arch derived by CFD using 3D-CT. The maximum WSS value may have an important role in the underlying mechanism of not only aortic atherosclerosis, but also aortic RP.

University hospitals, general hospitals, private clinics: Place-based differences in patient characteristics and outcomes of AF-A SAKURA AF Registry Substudy.

BACKGROUND: Relations between characteristics and outcomes of patients in Japan with atrial fibrillation (AF) and the type of medical facility providing their outpatient care are unclear. METHODS AND RESULTS: We compared patient characteristics and outcomes between 2 university hospitals (n=1178), 20 general hospitals (n=1308), and 41 private clinics (n=751) (follow-up: 39.3 months) in the prospective SAKURA AF Registry. Private clinic patients were significantly older than university hospital and general hospital patients (73.4±9.2 vs. 70.3±9.8 and 72.6±8.9 years; p<0.001), and these patients' CHADS2 scores were significantly lower than general hospital, but higher than university hospital patients (1.8±1.1 vs. 2.0±1.2 and 1.6±1.1; p<0.001). The Kaplan-Meier incidences of stroke/systemic embolism (SE) (1.72 vs. 1.58 vs. 0.84 events per 100 patient-years; p=0.120), a cardiovascular event (4.09 vs. 2.44 vs. 1.40; p<0.001), and death were higher (2.39 vs. 2.21 vs. 1.24; p=0.015) for university and general hospital patients than for private clinic patients; the incidences of major bleeding were equivalent (1.78 vs. 1.33 vs. 1.16; p=0.273). After multivariate adjustments, this trend persisted. CONCLUSIONS: Adverse clinical events at small to large hospitals appear to be higher than those at private clinics, suggesting that careful attention for preventing stroke/SE and cardiovascular events should be paid to patients at a university or general hospital.

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry.

BACKGROUND: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. METHODS: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). RESULTS: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31-2.25) and all-cause mortality (HR 1.43; 95% CI 1.06-1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). CONCLUSIONS: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.

Microphase separation in nanocomposite gels.

Microphase separation in poly(N-isopropylacrylamide)(PNIPA)-clay nanocomposite hydrogels (NC gels) is investigated by means of contrast-variation small-angle neutron scattering (CV-SANS) and dynamic light scattering (DLS). By using CV-SANS, it is revealed that microphase separation occurs in NC gels above the lower-critical solution temperature (LCST) of PNIPA aqueous solutions. The observed partial scattering functions show that only the spatial distribution of PNIPA chains is highly distorted by microphase separation and PNIPA chains are preferentially adsorbed on the clay surfaces, where the PNIPA-rich phase forms nanoscaled bicontinuous structure mediated by the clay particles. Additional DLS measurements for dilute solutions with PNIPA and/or the clay nanoparticles confirm that aggregation of PNIPA above the LCST is dramatically suppressed by addition of clay particles. Based on these observations, we conclude that strong affinity between the polymer and clay has a significant effect on the phase separation in NC gels and allows one to tune the length scale of the phase separation phenomenon by clay concentration.

Perspectives of value-based policy making in child health care in Japan.

In Japan, epidemiological transition has profoundly influenced the priorities of child healthcare. As pediatric care is shifting from a disease-driven curative approach to an integrated approach, the value of child health care now needs to be redefined with an integrated scope. With the trend to emphasize a rational judgement on the social value in terms of resource allocation and health policy, a value-based approach is necessary for child health care. This study aims to provide an overview and perspective of value-based policy making in child health care, under a context of epidemiological transition, health care system and social changes. The current methodology scheme of CEA and outcome evaluation has limitations, not meeting the urgent need of the application. The outcomes of child health care are no longer limited in clinical and health indicators such as survival rate, cure rate and health related quality of life, but also various aspects other than health, such as education, well-being of children and their primary caregivers, especially when treatment of diseases is no longer the dominant role of health care. Such the evaluation should reflect the impacts of the integrated approach in a long-term scope.

Adverse clinical events in Japanese atrial fibrillation patients with and without coronary artery disease-findings from the SAKURA AF Registry.

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD are limited.Methods: The SAKURA AF Registry is a prospective multi-center registry created to investigate outcomes of oral anticoagulant (OAC) use in Japanese AF patients. A study was conducted involving 3237 enrollees from 63 Tokyo-area institutions who were followed up for a median of 39.3 months. Clinical adverse events were compared between the patients accompanied with (n = 312) and without CAD (n = 2925).Results: The incidence of cardiovascular events and all-cause mortality rates were significantly higher among patients with CAD than among those without CAD (5.98 vs 2.52 events per 100 patient-years, respectively, p < 0.001; 3.27 vs 1.94 deaths per 100 patient-years, respectively, p = 0.012), but there was no difference in strokes/transient ischemic attacks or systemic embolisms (1.70 vs 1.34). After a multivariate adjustment, CAD remained a risk factor for cardiovascular events (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.08-2.25, p = 0.018). Among CAD patients, the propensity score-adjusted risk for major bleeding was significantly decreased among direct oral anticoagulant (DOAC) users in comparison to that among warfarin users (HR = 0.29, 95% CI = 0.07-0.94, p = 0.04), but other adverse clinical events did not differ significantly between these two groups.Conclusions: CAD did not appear to be a major determinant of strokes/TIAs, major bleeding, or all-cause mortality, but appeared to increase the risk of cardiovascular events in Japanese AF patients. The risk of major bleeding in CAD patients appeared to decrease when a DOAC rather than warfarin was administered. The data suggested that patients with AF and concomitant CAD require careful management and follow-up to reduce cardiovascular risks, and DOACs may be a better choice over warfarin when considering the risk of major bleeding.

Angioscopic differences of coronary intima between diffuse and focal coronary vasospasm: Comparison of optical coherence tomography findings.

BACKGROUND: Coronary artery vasospasm (CS) can be identified as either a diffuse type or focal type; however, the difference in endothelial characteristics between these spasm types remains unclear. The features of coronary intima associated with diffuse spasm and focal spasm using coronary angioscopy (CAS) were evaluated and the optical coherence tomography (OCT) findings were compared. METHODS: CAS and/or OCT observational analysis was performed in 55 patients (mean age: 61.4 years, 31 men) who had acetylcholine-provoked CS (diffuse CS, 31 patients; focal CS, 24 patients). The yellowness of the intima, presence of thrombus in CAS, and intimal characteristics based on the OCT results were evaluated. RESULTS: CAS showed more atherosclerotic yellow plaques at the focal spasm segment than at the diffuse spasm segment (p=0.032). Moreover, there were more thrombi at the focal spasm segment (p=0.039). In addition, OCT results revealed that the intima area, maximum intima thickness, and lipid content in the focal CS group were larger than the diffuse CS group (4.22±1.67mm2 vs. 3.45±2.36mm2; 0.71±0.29mm vs. 0.53±0.30mm; 55.9% vs. 32.0%, p<0.001, respectively). CONCLUSIONS: These results indicate that the presence of atherosclerotic plaques at the spasm site is likely to be related to the occurrence of a focal vasospasm. This may support the difference of features between focal CS and diffuse CS and contribute to precise treatment for each spasm type.