Risk factors for coronary artery abnormalities and resistance to immunoglobulin plus ciclosporin A therapy in severe Kawasaki disease: subanalysis of the KAICA trial, randomized trial for cicrosporin A as the first-line treatment.

Background: To investigate risk factors for coronary arterial abnormalities (CAAs) and resistance to treatment in patients with Kawasaki disease (KD) receiving intravenous immunoglobulin (IVIG) plus ciclosporin A (CsA) as the first-line treatment, we performed a subanalysis of baseline data of participants in the KAICA trial, a phase 3, randomized study (JMA-ILA00174). Methods: All data of the patients enrolled in the KAICA trial, who had a Gunma score ≥5 at diagnosis and had been randomly assigned to either IVIG (2 g/kg/24 h) plus CsA (5 mg/kg/day for 5 days) (n = 86) or IVIG alone (n = 87), were subjected to this study. CAA was defined by a Z score ≥2.5 observed within 4 weeks after treatment initiation. Baseline data including genotypes of KD susceptibility genes were compared between subgroups of patients for CAA or treatment response for each treatment group. Backword-forward stepwise logistic regression analyses were performed. Results: Pre-Z-max, defined as the maximum among Z scores on four coronary artery branches before treatment, was higher in patients with CAA in both treatment groups and was associated with CAA in IVIG plus CsA treatment group [odds ratio (OR) = 17.0]. High serum total bilirubin level was relevant to treatment resistance only in the IVIG plus CsA group (OR = 2.34). Conclusions: Coronary artery enlargement before treatment is a major determinant of CAA even in KD patients treated with initial IVIG treatment intensified by addition of CsA. Baseline serum total bilirubin level was a risk factor associated with resistance to IVIG plus CsA.

Analysis of Age, Sex, Lack of Response to Intravenous Immunoglobulin, and Development of Coronary Artery Abnormalities in Children With Kawasaki Disease in Japan.

Importance: Initial intravenous immunoglobulin (IVIG)-refractory status and prolonged fever are established risk factors for the development of coronary artery abnormalities (CAAs) among patients with acute-phase Kawasaki disease (KD). However, whether different risk factors exist for initial unresponsiveness to IVIG and CAA development remains unclear. Objective: To evaluate whether different risk factors exist for initial unresponsiveness to IVIG and CAA development among patients with KD (stratified by age at disease onset). Design, Setting, and Participants: This retrospective cohort study included a consecutive sample of 2414 patients from a database of patients with KD from October 1, 1999, to September 30, 2019. The data were based on annual surveys (response rate, 100%) using hospital medical records across Wakayama Prefecture, Japan. Data were analyzed from March 6 to March 26, 2022. Exposures: The patient's age and diagnosis of KD by board-certified pediatricians using the criteria established by the Japan KD Research Committee. Main Outcomes and Measures: Initial unresponsiveness to IVIG, defined as treatment with optional or advanced therapies, and development of CAAs. Echocardiograms performed 1 month after KD onset using the Japanese Ministry of Health criteria evaluated the presence or absence of CAAs. Odds ratios (ORs) with 95% CIs of patient age at KD onset for unresponsiveness to IVIG and developing CAAs were calculated using multivariable logistic regression models. Results: A total of 2414 patients (1403 male patients [58.1%]; median age at onset of KD, 25 months [range, 1-212 months]) were included in the study: 550 younger than 12 months, 1342 aged 12 to 47 months, and 522 older than 47 months. A total of 535 patients (22.2%) received optional or advanced treatment and 68 patients (2.8%) developed CAAs 1 month after disease onset. The sex-adjusted OR among patients younger than 12 months for unresponsiveness to IVIG was 0.77 (95% CI, 0.59-0.99) and for development of CAAs was 1.94 (95% CI, 1.07-3.52); among those older than 47 months, the OR for unresponsiveness to IVIG was 1.32 (95% CI, 1.05-1.67) and for development of CAAs was 2.47 (95% CI, 1.39-4.39). After adjusting for IVIG administration, ORs among boys older than 47 months for unresponsiveness to IVIG was 1.14 (95% CI, 0.84-1.56) and for development of CAAs was 2.15 (95% CI, 1.08-4.30); among girls younger than 12 months, the OR for unresponsiveness to IVIG was 1.02 (95% CI, 0.65-1.60) and for development of CAAs was 3.79 (95% CI, 1.21-11.90). Conclusions and Relevance: The results of this study suggest that risks of unresponsiveness to IVIG and the development of CAAs differ between infants with KD and older patients with KD. Residual risk factors for KD-related CAAs other than initial unresponsiveness to IVIG should be addressed, particularly in infants.

Drug offenses in the Tokyo Metropolitan Area: Trends for 2016-2018.

In Japan over the past few years, approximately 13,000 individuals were arrested for drug offenses each year. It is useful to know the trends in drug offenses, in order to devise the most effective countermeasures and addiction treatment programs. Herein, we have revealed the trends in drug offenses in the Tokyo Metropolitan Area. This report was researched the number of individuals arrested for drug offenses in Tokyo during the 3-year study period 2016-2018. The drugs are classified into the six categories: stimulants, narcotics, psychoactive drugs, opium, cannabis, and designated substances. We also calculated the percentages of individuals arrested for various drug offenses based on these six categories. Approximately 86% of the arrests for drug offenses in Tokyo during the 3-year period were for stimulants or cannabis. A higher percentage of individuals were arrested for stimulants, but the percentage of individuals arrested for cannabis increased each year. Given the percentage of individuals arrested for designated substances or narcotics, preventive measures for drug offenses involving stimulants and cannabis should be promptly implemented. Further campaigns to prevent drug offenses and public lectures are also needed. Public education must be provided to prevent drug offenses involving designated substances and narcotics.

Association between Depressive State and Lifestyle Factors among Residents in a Rural Area in Japan: A Cross-Sectional Study.

For the prevention of suicides, the early detection of depression symptoms and the implementation of suicide prevention measures based on the local community's conditions are critical. In rural or remote communities with poor access to urban areas, the medical care is often insufficient. We conducted the present study to investigate the relationship between depressive state and social-environmental factors in a depopulated inland rural area in central Japan, where the suicide rate is high and specialized psychiatric care is not available. Using a correspondence analysis, logistic regression analysis, and structural equation modeling (SEM), we examined the questionnaire responses of 912 residents (average 60.5 years old). Total Health Index-Depression (THI-D) scale scores were used to measure depressive state. The lifestyle-related factor with the strongest link to depressive state was 'concerns about interpersonal relationships' (OR = 2.7, 95% CI: 2.06-3.53, p < 0.0001), whereas financial concerns, number of friends, exercise habits, and perceived amount of sleep were also useful for predicting depressive state. The SEM showed that one's job and private life, particularly concerns about interpersonal relationships, are correlated with higher THI-D scores. Thus, social and lifestyle factors (e.g., concerns about interpersonal relationships and financial situation) can be used to predict depressive state in a depopulated rural area, and the newly revealed order in which depressive symptoms manifest is important. Our findings can be used to advance assessments of depressive symptoms and will be useful for mental health and suicide prevention.