This retrospective cohort study used the Diagnosis Procedure Combination database . All 82 academic hospitals were required to participate in the database. Data for approximately 8 million hospitalized patients of all ages are collected every year, equivalent to approximately 50% of the total number of acute-care hospitalizations in Japan. The database included the following information: unique identifiers of hospitals, patient baseline characteristics, diagnosis at admission, comorbidities at admission, and complications after admission recorded with text data in Japanese and International Classification of Diseases, Tenth Revision (ICD-10) codes. The database also contains information on medical procedures and treatments (including drug administration, device use, and surgical and nonsurgical procedures) based on the original Japanese codes, length of stay, discharge status, and medical costs during hospitalization. Attending physicians must confirm all diagnoses and comorbidities.
Furthermore, because accurate reporting is linked with the payment system in Japan, attending physicians and hospitals are required to accurately report diagnoses and comorbidities. This study was approved by the Institutional Review Board of the University of Tokyo (approval number: 3501-(3); December 25, 2017). The requirement for informed consent was waived because of the anonymity of the data.
We used this database to identify patients diagnosed with KD (ICD-10 code: M303) between July 2010 and March 2020. We included patients who received at least 2 g of intravenous immunoglobulin (IVIG). Atypical KD is generally defined as KD that does not meet the full criteria. Typically, patients with atypical KD have fever (even within 5 days) and only two or three major clinical manifestations. In the database, diagnoses were recorded using Japanese text and ICD-10 codes, and physicians described whether KD was the atypical type in the Japanese text. We excluded those with a weight < 3 kg, missing data, or "suspected" KD.
We identified AARF patients with a diagnosis of AARF (ICD-10 code: M4361) or the text data of "AARF" in Japanese. KD patients who were not diagnosed with AARF but were treated conservatively for AARF were also regarded as AARF patients.
We compared patient backgrounds between patients who had AARF and those who did not.
The patients’ backgrounds were investigated, including age, sex, weight, height, body mass index (BMI), hospital days at initial IVIG (i.e., the interval from the admission day to the day when the initial IVIG was administered), atypical KD or not , type of hospital (academic hospital or not), complex chronic conditions (classified based on the definitions reviewed in a previous study ), transportation by ambulance, Japan Coma Scale at admission, transportation from other hospitals, and hospital volume. The Japan Coma Scale score at admission was categorized into two groups: alert and not alert. The Japan Coma Scale assessment was previously shown to be associated with the Glasgow Coma Scale assessment . The hospital volume was defined as the number of patients with KD at each hospital every year. We separated the included patients into tertiles of hospital volume so that the number of patients in each group was almost equal.
Categorical variables are shown as numbers and percentages and were compared between groups with and without AARF using Fisher’s exact test. Continuous variables are shown as the mean and standard deviation (SD) or median and interquartile range (IQR). We used t-tests to compare normally distributed variables and the Mann–Whitney U test to compare non-normally distributed variables (body mass index and hospital days at initial IVIG) between the groups with and without AARF.
Univariate and multivariate logistic regression analyses were performed to identify the factors associated with AARF in patients with KD. Dependent variables in the multivariable analysis were age, sex, BMI, hospital days of illness at initial IVIG, atypical KD or not, type of hospital, complex chronic conditions, transportation by ambulance, Japan Coma Scale score at admission, transportation from other hospitals, and hospital volume. Results were presented as odds ratios (ORs) and 95% confidence intervals (CIs).
We compared the proportion of coronary artery abnormalities (CAAs), IVIG resistance, medical costs, and length of stay between patients with and without AARF. CAAs were identified with a recorded diagnosis of CAAs (ICD-10 code: I254) or text data of CAAs in Japanese. IVIG resistance was defined as IVIG use at a total dose of ≥ 4.0 g/kg or a combination of any steroid, infliximab, cyclosporine, or plasma exchange that was not performed simultaneously with the initial IVIG treatment. We also performed multivariable logistic regression analyses for CAA and IVIG resistance and multiple regression analyses for the length of hospital stay and medical cost. The adjusted variables were age, sex, BMI, hospital days at initial IVIG, atypical KD, type of hospital, complex chronic conditions, transportation by ambulance, Japan Coma Scale at admission, transportation from other hospitals, and hospital volume.
For AARF patients with acute KD, we also examined whether the following treatments were performed during hospitalization: surgery (open reduction of cervical spine dislocation [Japanese surgical code: K118], dynamic stabilization of the spine [K141-3], and spinal decompression with or without fusion [K142]). Conservative treatment (cervical collar [Japanese treatment codes: J200], cervical traction [J118], halo-vest orthosis [K144], and closed reduction of the cervical spine [K117-2]). The patients' backgrounds in the surgery and conservative treatment groups were compared.
A two-sided p < 0.05 was considered significant. All statistical analyses were conducted using the Stata software (version 17.0; StataCorp LP, College Station, TX, USA).