Impact of the Stang Structure of Intensive Care Units and High Care Units on In-Hospital Mortality Among Patients with Sepsis: A Retrospective Analysis of Japanese Nationwide Claims Data

Background: Critical care in Japan is provided in intensive care units (ICUs) and high care units (HCUs), which are categorized based on their fulllment of different stang criteria. Under Japan’s medical fee reimbursement system, units with higher stang levels are eligible to receive higher reimbursements. However, the different stang structure of these units may affect the quality of care and patient outcomes. This study aimed to analyze the impact of ICU/HCU stang structure on in-hospital mortality among septic patients in Japan’s acute care hospitals using a nationwide claims database. Methods: We conducted a large-scale multicenter retrospective cohort study of adult septic patients (aged ≥ 18 years) who received critical care in acute care hospitals throughout Japan between April 2018 and March 2019. Patients were categorized into three groups according to the type of unit in which they received critical care: Type 1 ICUs (fullling stringent stang criteria such as experienced intensivists and high nurse-to-patient ratios), Type 2 ICUs (fullling less stringent criteria), and HCUs (fullling the least stringent criteria). A Cox proportional hazards regression model was constructed with in-hospital mortality as the dependent variable and the ICU/HCU groups as the main independent variable of interest. Other covariates included age, emergency or non-emergency admission, major diagnostic categories, mechanical ventilation, noninvasive positive airway pressure ventilation, oxygen therapy, and renal replacement therapy. Results: We analyzed 2411 patients (178 hospitals) in the Type 1 ICU group, 3653 patients (422 hospitals) in the Type 2 ICU group, and 4904 patients (521 hospitals) in the HCU group. When compared with the HCU group, the adjusted hazard ratios for in-hospital mortality were 0.74 (95% condence interval: 0.71–0.77; P<0.001) for the Type 1 ICU group and 0.83 (0.80–0.85; P<0.001) for the Type 2 ICU group. Emergency hospital admission had the highest hazard ratio for in-hospital mortality (hazard ratio: 4.78; P<0.001). Conclusions: ICUs that fulll more stringent stang criteria were associated with lower in-hospital mortality in septic patients than HCUs after adjusting for confounders. Optimizing the stang structure of these units may contribute to the improvement of patient outcomes. and Type 2 ICU group (3.9%) group (2.2%). to the majority of patients in the Type group and Type 2 ICU group (70.7%), but to less than half of all patients in the group


Introduction
Sepsis refers to a dysregulated host response to infection resulting in potentially fatal organ dysfunction [1], and is associated with heavy clinical and economic burdens throughout the world [2,3]. Due to the high risk of rapid deterioration, this syndrome requires prompt and intensive treatment (e.g., antibiotic therapy, uid resuscitation, and supplemental oxygen) [4]. Optimal sepsis care is therefore dependent on the availability of an effective health care provision system with adequate resources.
Donabedian's structure-process-outcome model is a well-established approach for assessing health care quality [5], and has been applied in the elds of critical care and emergency care [6][7][8][9][10]. The sta ng characteristics of intensive care units (ICUs) can be analyzed as part of the "structure" component of Donabedian's triad. Among Japan's acute care hospitals, critical care is provided in ICUs and high care units (HCUs). While HCUs share some similarities in organization and function with the high-dependency units of other countries, many Japanese hospitals that lack ICUs treat critically ill patients in HCUs. The de nitions of ICUs and HCUs are set by Japan's medical fee reimbursement system and are based on the units' sta ng structure, such as the availability and experience of medical staff (Table 1). Under this system, ICUs are divided into two types, with Type 1 ICUs ful lling more stringent sta ng criteria and receiving higher reimbursements than Type 2 ICUs. Furthermore, both ICU types are entitled to receive higher reimbursements than HCUs, which ful ll less restrictive criteria. Despite these differences in sta ng structure, studies have yet to explore the differences in the quality of care provided to septic patients among these units. This study aimed to analyze the impact of the sta ng structure of ICUs and HCUs on in-hospital mortality among septic patients in Japan's acute care hospitals.

Study design and data source
We conducted a multicenter retrospective observational study of adult patients with sepsis who were admitted to an ICU or HCU between April 1, 2018 and March 31, 2019. The patients were divided into three groups according to the unit in which they received critical care: Type 1 ICUs, Type 2 ICUs, and HCUs. In addition to sta ng criteria, these units are also categorized based on the monthly proportion of admitted patients who ful ll speci c evaluation criteria for medical and nursing care needs (Supplementary Table 1).
The data source was a DPC database extracted from the NDB. DPC data comprise clinical information and claims data, and include patient demographics (e.g., age, sex, height, and weight), primary and secondary diagnoses, dates of admission and discharge, comorbidities, treatments (e.g., mechanical ventilation, renal replacement therapy, and vasopressor administration), and discharge status. Details on ICU and HCU utilization are also included.

Patient selection
Septic patients were identi ed as those with the relevant International Classi cation of Diseases, 10th Revision codes upon admission or during hospitalization ( Table 2). The dates of ICU/HCU admission were determined based on Japanese treatment codes provided in the claims data. We excluded patients who were not yet discharged from hospital during the study period, patients aged below 18 years, and patients with missing age data.

Patient characteristics and treatments
We collected information on the following patient baseline characteristics: age, sex, hospital admission course (emergency or non-emergency), and major diagnostic category. Furthermore, the use of mechanical ventilation, noninvasive positive pressure ventilation, high-ow oxygen therapy, renal replacement therapy, endotoxin absorption, tracheotomy, adrenaline, noradrenaline, and vasopressin were identi ed from the corresponding Japanese procedural codes. Patients with acute respiratory distress syndrome (ARDS) were identi ed using the International Classi cation of Diseases, 10th Revision code J80.

Outcome measures
The study's primary outcome measure was in-hospital mortality, and the secondary outcome measures were ICU/HCU stay (days) and overall hospital stay (days).

Statistical analysis
Continuous variables were calculated as means and standard deviations, and categorical variables were calculated as numbers and percentages. One-way analysis of variance and the Chi-squared test were used to compare the continuous and categorical variables, respectively, among the three ICU/HCU groups (Type 1 ICUs, Type 2 ICUs, and HCUs). We plotted Kaplan-Meier survival curves to examine the differences in survival among the three groups.
Univariate analyses were performed to identify patient characteristics and treatments that were signi cantly associated (P < 0.05) with in-hospital mortality; these characteristics were included as covariates in a Cox proportional hazards regression model with in-hospital mortality as the dependent variable and the ICU/HCU groups as the main independent variable of interest. The hazard ratios (HRs) and 95% con dence intervals (CIs) were calculated for the independent variables. In addition, subgroup analyses were performed for patients with (a) sepsis-induced ARDS, (b) sepsis induced by methicillinresistant Staphylococcus aureus (MRSA), and (c) sepsis with blood, blood-forming organs, and immunological disorders. P values lower than 0.05 were considered to be statistically signi cant. All analyses were performed using SPSS Version 26.0 (IBM Japan, Ltd., Tokyo, Japan). Figure 1 shows the owchart of patient selection. From among 671,425 patients admitted to an ICU or HCU in 900 hospitals, we identi ed 32,690 patients with a recorded diagnosis of sepsis. We then excluded 19,956 patients who were not discharged during the study period, 161 patients aged below 18 years, and 1605 patients with missing age data. The nal analysis was conducted using 10,968 patients in 861 hospitals. Of these, 2411 patients (178 hospitals) were treated in a Type 1 ICU, 3653 patients (422 hospitals) were treated in a Type 2 ICU, and 4904 patients (521 hospitals) were treated in an HCU.

Results
The patient characteristics and treatments are summarized in Table 3. The mean ages of the patients in the Type 1 ICU group, Type 2 ICU group, and HCU group were 72.1 years, 73.6 years and 76.8 years, respectively (P < 0.001). There were also signi cant intergroup differences in sex and emergency admissions. In all groups, men accounted for the majority of patients, and emergency admissions comprised more than 80% of cases. Among the treatments, the use of mechanical ventilation was signi cantly higher (P < 0.001) in the Type 1 ICU group (58.4%) and Type 2 ICU group (55.0%) than in the HCU group (28.2%). However, there was no signi cant intergroup difference (P = 0.11) in the duration of mechanical ventilation. High-ow oxygen therapy was used more often than noninvasive positive pressure ventilation in all three groups. The use of tracheotomy was signi cantly higher (P < 0.001) in the Type 1 ICU group (5.1%) than in the HCU group (1.7%). Similarly, the use of renal replacement therapy was signi cantly higher (P < 0.001) in the Type 1 ICU group (36.3%) and Type 2 ICU group (31.7%) than in the HCU group (14.4%). Furthermore, the use of endotoxin adsorption was signi cantly higher (P < 0.001) in the Type 1 ICU group (5.2%) and Type 2 ICU group (3.9%) than in the HCU group (2.2%). Noradrenaline was administered to the majority of patients in the Type 1 ICU group (75.8%) and Type 2 ICU group (70.7%), but to less than half of all patients in the HCU group (46%) (P < 0.001).  Table 3 also presents the outcomes of each group. There was no signi cant difference (P = 0.05) in ICU/HCU stay among the groups (mean ± standard deviation: 4.5 ± 3.5 days in the Type 1 ICU group, 4.2 ± 3.4 days in the Type 2 ICU group, and 4.3 ± 3.9 days in the HCU group). There was also no signi cant difference (P = 0.12) in overall hospital stay among the groups (mean ± standard deviation: 23.1 ± 23.8 days in the Type 1 ICU group, 22.3 ± 21.9 days in the Type 2 ICU group, and 22.0 ± 21.3 days in the HCU group). However, there was a signi cant difference (P < 0.001) in unadjusted in-hospital mortality among the groups (46.3% in the Type 1 ICU group, 48.5% in the Type 2 ICU group, and 37.7% in the HCU group). Table 4 presents the major diagnostic categories of the patients. In all groups, the most prevalent category was "digestive system, hepatobiliary system, and pancreas". This was followed by "circulatory system", "respiratory system", and "blood, blood-forming organs, and immunological disorders". Before statistical adjustment, the HCU group had the highest survival rate. However, the two ICU groups had higher survival rates than the HCU group after adjusting for the covariates using the Cox proportional hazards model (Type 1 ICU group versus Type 2 ICU group, P < 0.001; Type 1 ICU group versus HCU group, P < 0.001; and Type 2 ICU group versus HCU group, P < 0.001) (Fig. 3). The results of the Cox proportional hazards analysis of in-hospital mortality are provided in Table 5. The ICU/HCU groups were signi cantly associated with in-hospital mortality after adjusting for the covariates (P < 0.001). When compared with the HCU group, the HRs for in-hospital mortality were 0.74 (95% CI: 0.71-0.77; P < 0.001) for the Type 1 ICU group and 0.83 (95% CI: 0.80-0.85; P < 0.001) for the Type 2 ICU group. Emergency hospital admission had the highest hazard ratio for in-hospital mortality (hazard ratio: 4.78; P < 0.001). The subgroup analysis results are provided in Table 6. When the samples were limited to sepsis-induced ARDS (n = 1395) or MRSA-induced sepsis (n = 760), the ICU/HCU groups were not signi cantly associated with in-hospital mortality (sepsis-induced ARDS: P = 0.12; MRSA-induced sepsis: P = 0.10). However, ICU/HCU groups remained a signi cant determinant of in-hospital mortality for cases of sepsis with blood, blood-forming organs, and immunological disorders (n = 896; P < 0.001).

Discussion
In this large-scale analysis of national-level claims data, we comparatively examined in-hospital mortality in septic patients among ICUs and HCUs designated by Japan's medical fee reimbursement system. Both ICU types were associated with signi cantly reduced hazards of in-hospitality mortality when compared to HCUs, with Type 1 ICUs (ful lling more stringent sta ng criteria) demonstrating a lower hazard than Type 2 ICUs.
In 2015, the American College of Critical Care Medicine Task Force on Models of Critical Care recognized that improvements in ICU structure can lead to better patient outcomes, and noted that a dedicated intensivist-led multidisciplinary team is integral to the effective delivery of critical care [12]. ICUs can be categorized as "open" or "closed", with the key difference being that only ICU intensivists can direct care and write medical orders in a closed ICU [13,14]. A US study reported that closed ICUs were associated with lower mortality in patients with acute lung injury [15]. Similarly, a Japanese study of septic patients found that closed ICUs were associated with increased survival and shorter ICU stays when compared with open ICUs [16]. A meta-analysis of open and closed ICUs also found that the former had signi cantly higher mortality rates than the latter for a variety of health conditions [17]. In our study, ICU/HCU sta ng structure was determined based on sta ng criteria. However, we could not ascertain the actual sta ng numbers or the authority of intensivists in each unit, and were therefore unable to determine if each unit operated in an open or closed format. Nevertheless, the medical fee reimbursement system provides objective criteria that enabled us to categorize the ICUs and HCUs according to sta ng factors. These criteria include the experience of intensivists and ICU nurses, as well as the availability of specialist staff. Our analysis detected signi cant differences in in-hospital mortality among the unit types, suggesting that the presence of dedicated intensivists, nurses, and medical technologists in critical care units can contribute to improved patient outcomes. These ndings are consistent with those of previous studies on the sta ng structure of critical care [12,[15][16][17].
Among our subjects, mortality was particularly high in septic patients with blood, blood-forming organs, and immunological disorders. This corroborates the results of a previous study where hematological malignancies were associated with an increased hazard for sepsis and one-year mortality [18]. Another study reported an association between hematological malignancies and higher 28-day mortality in septic patients requiring ICU admission [19]. Our present study found that treatment in Type 1 ICUs was associated with reduced in-hospital mortality for such patients, suggesting that higher sta ng levels with more experienced specialists can affect outcomes even in severe cases with blood and immunological disorders.
Previous studies have shown that ICU structural factors are also associated with other processes and outcomes of care. For example, sta ng characteristics (including the presence of expert intensivists and dedicated pharmacists) have been linked with shorter mechanical ventilation durations [20]. Furthermore, regular examinations by intensivists in ICUs were found to be associated with the achievement of lighter sedation goals [21]. Another study determined that nurse-driven weaning from mechanical ventilation signi cantly reduced ventilation durations and ICU stay without adverse effects [22]. In contrast to those previous studies, our analysis found no signi cant differences in mechanical ventilation duration among the ICU/HCU groups. This may be because our observational study was based on sta ng criteria, and did not account for the actual treatment strategies employed for each case. The presence and distribution of staff alone may not directly affect mechanical ventilation strategies in Japan's ICUs and HCUs, but further research is needed to explore this relationship.
This study has several limitations. First, there was a lack of information on each patient's blood examination results. Due to the lack of physiological data in the DPC database, we could not assess indicators such as leukocyte count, C-reactive protein levels, oxygenation levels, and blood pressure.
Second, we could not compare Sequential Organ Failure Assessment scores among the groups because This research did not receive any funding from agencies in the public, commercial, or not-for-pro t sectors.
Availability of data and materials The data set used in this study is available from the corresponding author on reasonable request.

Ethics approval and consent to participate
This study was conducted in accordance with the principles of the Declaration of Helsinki, and was approved by the institutional review board of Kansai Medical University Hospital (Approval Number: 2019078). The requirement for informed consent from patients was waived given the retrospective design of the study and the use of anonymized patient and hospital data.

Consent for publication
Not applicable.