BACKGROUND: Medical advances in intensive care units (ICUs) have resulted in the emergence of a new patient population-those who survive the initial acute phase of critical illness, but require prolonged ICU stays and develop chronic critical symptoms. This condition, often termed Persistent Critical Illness (PerCI) or Chronic Critical Illness (CCI), remains poorly understood and inconsistently reported across studies, resulting in a lack of clinical practice use. This scoping review aims to systematically review and synthesize the existing literature on PerCI/CCI, with a focus on definitions, epidemiology, and outcomes for its translation to clinical practice. METHODS: A scoping review was conducted using MEDLINE and Scopus, adhering to the PRISMA-ScR guidelines. Peer-reviewed original research articles published until May 31, 2024 that described adult PerCI/CCI in their definitions of patient populations, covariates, and outcomes were included. Data on definitions, epidemiology, and outcomes were extracted by a data charting process from eligible studies and synthesized. RESULTS: Ninety-nine studies met the inclusion criteria. Of these studies, 64 used the term CCI, 18 used PerCI, and 17 used other terms. CCI definitions showed greater variability, while PerCI definitions remained relatively consistent, with an ICU stay ≥ 14 days for CCI and ≥ 10 days for PerCI being the most common. A meta-analysis of the prevalence of PerCI/CCI among the denominators of "all ICU patients", "sepsis", "trauma", and "COVID-19" showed 11% (95% confidence interval 10-12%), 28% (22-34%), 24% (15-33%), and 35% (20-50%), respectively. A meta-analysis of in-hospital mortality was 27% (26-29%) and that of one-year mortality was 45% (32-58%). Meta-analyses of the prevalence of CCI and PerCI showed 17% (16-18%) and 18% (16-20%), respectively, and those for in-hospital mortality were 28% (26-30%) and 26% (24-29%), respectively. Functional outcomes were generally poor, with many survivors requiring long-term care. CONCLUSIONS: This scoping review synthesized many studies on PerCI/CCI, highlighting the serious impact of PerCI/CCI on patients' long-term outcomes. The results obtained underscore the need for consistent terminology with high-quality research for PerCI/CCI. The results obtained provide important information to be used in discussions with patients and families regarding prognosis and care options.

BACKGROUND: Hybrid emergency department (ED), which are equipped with fluoroscopy and computed tomography has been developed in Japan as a novel emergency care room. Although hybrid ED is effective in improving the outcomes of severe trauma, its influence on the management of out-of-hospital cardiac arrest (OHCA) requiring extracorporeal cardiopulmonary resuscitation (ECPR) remains unclear. OBJECTIVES: The aim of this study was to elucidate the impact of hybrid ED on ECPR procedures and outcome in OHCA patients focusing on time from hospital arrival to establishment of ECPR. METHODS: A retrospective single-center cohort study was conducted, including adult OHCA patients who underwent ECPR between April 2013 and March 2022. Patients treated in conventional ED were compared with those in hybrid ED. Primary outcome was time from hospital arrival to ECPR initiation. Secondary outcomes included favorable neurological outcome at 30 days and incidence of cannulation-related adverse events. RESULTS: Hybrid ED installation led to a significant decrease in time to ECPR initiation. In the interpreted time series analysis for the time from hospital arrival to establishment ECPR, there was statistically significant upward level change and downward trend change after the installation of hybrid ED. These results mean the time from hospital arrival to the establishment of ECPR was prolonged just after installation of hybrid ER, and the time from hospital arrival to the establishment of ECPR was shortened over time. There were no statistically significant differences between the conventional and hybrid ED groups on the favorable neurological outcome and cannulation-related adverse events. CONCLUSIONS: The installation of hybrid ED was associated with shortened time from hospital arrival to establishment of ECPR. Further evaluation is needed to elucidate the effects of hybrid ED on OHCA and determine an optimal strategy.

Background Nursing home residents with a high risk of multidrug-resistant organism infection pose a complex challenge to broad-spectrum empirical antimicrobial therapy, particularly those infected with extended-spectrum β-lactamase-producing Enterobacteriaceae. The present study compared the efficacy of piperacillin-tazobactam and carbapenems as empirical antimicrobial treatments for patients with sepsis from nursing homes. Patients and Methods Using a nationwide inpatient database in Japan, we identified patients diagnosed with sepsis within two days of admission from nursing homes between 2018 and 2021. We selected patients who received intravenous piperacillin-tazobactam or carbapenems within two days of admission. In-hospital mortality was compared between the piperacillin-tazobactam and carbapenem groups using inverse probability of treatment weighting. Result We identified 8,025 eligible patients. Of these, 3,391 (42%) received piperacillin-tazobactam, and 4,634 (58%) received carbapenems within 2 days of admission. The inverse probability of treatment weighting analysis showed no significant difference in in-hospital mortality between the groups (31.6% in the piperacillin-tazobactam group and 32.8% in the carbapenem group; risk difference, 1.2%; 95% confidence interval, -3.2% to 0.9%). Conclusions Carbapenems and piperacillin-tazobactam as empirical antimicrobial therapy in patients with sepsis from nursing homes were associated with comparable in-hospital mortality rates. These findings highlight the importance of making decisions regarding broad-spectrum empirical antimicrobial therapy.

OBJECTIVE: To elucidate the demographics, clinical characteristics, and outcomes of patients with postpartum hemorrhage (PPH) who underwent transcatheter arterial embolization (TAE). METHODS: We conducted a retrospective observational study using the Japanese Diagnosis Procedure Combination inpatient database, which covers roughly 90% of all tertiary emergency hospitals in Japan, between April 2012 to March 2020. We identified patients with PPH who underwent TAE using the Japanese medical procedure status and code, and the device or drug code. We examined the patient characteristics, interventions administered, and clinical outcomes. RESULTS: Among 64 893 patients diagnosed with PPH, we identified 2705 (4.2%) patients with PPH who underwent TAE. The most common cause of PPH was uterine atony (68.7%), followed by disseminated intravascular coagulation after labor (30.0%) and placenta accreta spectrum disorders (23.4%). The proportion of patients who underwent repeat TAE and a hysterectomy was 64 (2.4%) and 188 (7.0%), respectively. Among hysterectomies (n = 188), 26 (13.8%) had the procedure performed before TAE, 73 (38.8%) underwent hysterectomy on the same day as TAE, and 89 (47.4%) had the procedure conducted after TAE. Of those who underwent a hysterectomy after TAE (n = 89), 33 (37%) were performed more than 1-week after initial TAE. Overall in-hospital mortality was 14/2705 (0.5%). CONCLUSION: Even if hemostasis is achieved through TAE, one must be mindful that a hysterectomy may become necessary more than 1 week after the procedure. These results could be helpful in clinical decision making and providing patients with additional treatment options for PPH that preserve patient fertility.

Abstract Background There was no study to investigate the association between the national surge of Coronavirus disease 2019 (COVID-19) patients and the mortality of mechanically ventilated COVID-19 patients. The aim of this study was to assess the association between mortality in mechanically ventilated COVID-19 patients and two distinct national COVID-19 surge indices: (1) the daily number of newly confirmed COVID-19 cases, representing overall medical demands and (2) the total number of critically ill COVID-19 patients, reflecting critical care demands. Methods We analyzed the patient data registered in a national database of mechanically ventilated COVID-19 patients between February 6, 2020, and May 16, 2023, combined with the data officially published by the Japanese government. Multivariable logistic regression analysis was performed to evaluate the association of these two indices with COVID-19 mortality. A generalized linear mixed effect model was used to examine the relationships between the variation in the impact of critical care demands across hospitals and the variation in baseline risk across hospitals. Results The data of 8327 patients from 264 centers in Japan were analyzed. The overall mortality rate was 24% (1990/8327). The critical care demands, but not overall medical demands, were independently associated with the mortality (OR, 1.11; 95% CI 1.07–1.16; p < 0.001). This effect of critical care demands on the mortality was more pronounced in hospitals with higher baseline risk (r = 0.67). Conclusions The national critical care demands were independently associated with the mortality of COVID-19 patients requiring mechanical ventilation. This effect was more pronounced in hospitals with higher baseline risk.

OBJECTIVES: Polypharmacy is an important healthcare issue, especially in elderly patients with dementia. As an incentive to reduce polypharmacy, a health insurance reimbursement scheme was introduced in 2016 for medication review and the reduction of medications for inpatients in Japan. However, the effects of these incentive schemes were not evaluated. METHODS: We identified 1,465,881 inpatients aged ≥65 years with dementia. An interrupted time-series analysis was conducted by fitting a Prais-Winsten linear regression model. The outcome measure was the number of classes of medications prescribed during discharge. RESULTS: No significant changes were observed in the average number of medication classes at discharge immediately after the introduction of the scheme (coefficient: -0.022, 95% confidence interval [CI]: -0.17 to 0.13). The slope change, representing the effect of the intervention over time, was also not significant (coefficient: -0.00053, 95% confidence interval: -0.0012 to 0.00018). CONCLUSIONS: The incentive scheme was not associated with a reduction in the number of medication classes at discharge among older inpatients with dementia.

BACKGROUND: The micro-axial flow pump Impella, a new mechanical circulatory device for cardiogenic shock, is still only available in a limited number of hospitals, due to the facility certification requirements and insufficient evidence of the benefit of introducing Impella in hospitals. This study aimed to evaluate the impact of introducing Impella in hospitals on in-hospital mortality of patients treated with extracorporeal membrane oxygenation (ECMO). METHODS: Using a nationwide Japanese inpatient database, we identified patients who received ECMO during hospitalization between 1 April 2014 and 31 March 2021. A hospital-level propensity score-matched cohort was created matching hospitals that introduced Impella (exposure group) to those that did not introduce Impella (control group). The inclusion period in each hospital was divided into two time periods according to the time of Impella introduction in the exposure group and the corresponding hospital in the control group (before and after exposure). The primary outcome was in-hospital mortality. Uncontrolled and controlled interrupted time-series analyses involved before-after exposure comparison and exposure-control comparison. RESULTS: Out of 34,379 eligible patients, we created a matched cohort of 8351 patients from 86 hospitals with Impella introduction (exposure group) and 7230 patients from 86 hospitals without Impella introduction (control group). In-hospital mortality before and after exposure was 62.5% and 59.3, respectively, in the exposure group; and 66.8% and 63.7%, respectively, in the control group. Uncontrolled interrupted time-series analysis showed no significant level change or trend change in the before-after exposure comparison in both the exposure and the control groups. Controlled interrupted time-series analysis also showed no significant level change (-0.01%; 95% confidence intervals -5.36% to + 5.33%) or trend change (+ 0.10%, -0.30% to + 0.40%) after exposure in the exposure-control comparison. CONCLUSIONS: This nationwide inpatient database study showed no association between Impella introduction in hospitals and in-hospital mortality of patients who underwent ECMO. Because this study confined itself to analze of the impact of the introduction of Impella solely at the hospital level, further detailed studies are warranted to assess its efficacy at the patient level.

BACKGROUND: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time and outcomes in accidental hypothermia (AH) patients compared to those of patients without AH has not been fully investigated. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. We enrolled patients aged ≥ 18 years who had been admitted to the emergency department for OHCA and had undergone ECPR between January, 2013 and December, 2018. AH was defined as an arrival body temperature below 32 °C. The primary outcome was survival to discharge. Cubic spline analyses were performed to assess the non-linear associations between low-flow time and outcomes stratified by the presence of AH. We also analyzed the interaction between low-flow time and the presence of AH. RESULTS: Of 1252 eligible patients, 105 (8.4%) and 1147 (91.6%) were in the AH and non-AH groups, respectively. Median low-flow time was 60 (47-79) min in the AH group and 51 (42-62) min in the non-AH group. The survival discharge rates in the AH and non-AH groups were 44.8% and 25.4%, respectively. The cubic spline analyses showed that survival discharge rate remained constant regardless of low-flow time in the AH group. Conversely, a decreasing trend was identified in the survival discharge rate with longer low-flow time in the non-AH group. The interaction analysis revealed a significant interaction between low-flow time and AH in survival discharge rate (p for interaction = 0.048). CONCLUSIONS: OHCA patients with arrival body temperature < 32 °C who had received ECPR had relatively good survival outcomes regardless of low-flow time, in contrast to those of patients without AH.

BACKGROUND: Patients who receive invasive mechanical ventilation (IMV) in the intensive care unit (ICU) have exhibited lower in-hospital mortality rates than those who are treated outside. However, the patient-, hospital-, and regional factors influencing the ICU admission of patients with IMV have not been quantitatively examined. METHODS: This retrospective cohort study used data from the nationwide Japanese inpatient administrative database and medical facility statistics. We included patients aged ≥ 15 years who underwent IMV between April 2018 and March 2019. The primary outcome was ICU admission on the day of IMV initiation. Multilevel logistic regression analyses incorporating patient-, hospital-, or regional-level variables were used to assess cluster effects by calculating the intraclass correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV). RESULTS: Among 83,346 eligible patients from 546 hospitals across 140 areas, 40.4% were treated in ICUs on their IMV start day. ICU admission rates varied widely between hospitals (median 0.7%, interquartile range 0-44.5%) and regions (median 28.7%, interquartile range 0.9-46.2%). Multilevel analyses revealed significant effects of hospital cluster (ICC 82.2% and MOR 41.4) and regional cluster (ICC 67.3% and MOR 12.0). Including patient-level variables did not change these ICCs and MORs, with a PCV of 2.3% and - 1.0%, respectively. Further adjustment for hospital- and regional-level variables decreased the ICC and MOR, with a PCV of 95.2% and 85.6%, respectively. Among the hospital- and regional-level variables, hospitals with ICU beds and regions with ICU beds had a statistically significant and strong association with ICU admission. CONCLUSIONS: Our results revealed that primarily hospital and regional factors, rather than patient-related ones, opposed ICU admissions for patients with IMV. This has important implications for healthcare policymakers planning interventions for optimal ICU resource allocation.

OBJECTIVE: Previous studies show that the COVID-19 pandemic affected the number of surgeries performed. However, data on the association between the COVID-19 pandemic and otolaryngologic surgeries according to subspecialties are lacking. This study was performed to evaluate the impact of the COVID-19 pandemic on various types of otolaryngologic surgeries. METHODS: We retrospectively identified patients who underwent otolaryngologic surgeries from April 2018 to February 2021 using a Japanese national inpatient database. We performed interrupted time-series analyses before and after April 2020 to evaluate the number of otolaryngologic surgeries performed. The Japanese government declared its first state of emergency during the COVID-19 pandemic in April 2020. RESULTS: We obtained data on 348,351 otolaryngologic surgeries. Interrupted time-series analysis showed a significant decrease in the number of overall otolaryngologic surgeries in April 2020 (-3619 surgeries per month; 95% confidence interval, -5555 to -1683; p < 0.001). Removal of foreign bodies and head and neck cancer surgery were not affected by the COVID-19 pandemic. In the post-COVID-19 period, the number of otolaryngologic surgeries, except for ear and upper airway surgeries, increased significantly. The number of tracheostomies and peritonsillar abscess incisions did not significantly decrease during the COVID-19 pandemic. CONCLUSION: The COVID-19 pandemic was associated with a decrease in the overall number of otolaryngologic surgeries, but the trend differed among subspecialties.

INTRODUCTION: The clinical benefit of hemostasis molecular indicators such as thrombin-antithrombin complex (TAT), soluble fibrin (SF), and prothrombin fragment 1 + 2 (F1+2) for the diagnosis of disseminated intravascular coagulation (DIC) is reported. Recently, novel DIC diagnostic criteria that adopt them were proposed in Japan. Despite the theoretical understanding of their function, the practical use of these markers remains unclear. The present study aimed to provide a descriptive overview of current clinical practice regarding the measurement of hemostasis markers in sepsis management in Japan. METHODS: This retrospective observational analysis used the Japanese Diagnosis Procedure Combination inpatient database containing data from more than 1500 acute-care hospitals in Japan. We identified adult patients hospitalized for sepsis between April 2018 and March 2021. Descriptive statistics for measuring several hemostasis laboratory markers were summarized using patient disease characteristics, hospital characteristic, and geographical location. RESULTS: This study included 153,474 adult sepsis patients. Crude in-hospital mortality was 30.0%. Frequency of measurement of fibrinogen, fibrin degradation products (FDP), and D-dimer in sepsis patients on admission was 43.2%, 36.1%, and 46.4%, respectively. Novel and specific hemostasis molecular markers such as TAT, SF, and F1+2 were seldom measured (1.9%, 1.7%, and 0.02%, respectively). Hemostasis molecular markers were more frequently measured with progression of thrombocytopenia. Measurement of these clinically favorite hemostasis markers was influenced not only by disease characteristics but also hospital characteristic or geographical location. CONCLUSIONS: Hemostasis molecular markers such as TAT, SF, and F1+2 were rarely measured in clinical settings. Although adopted by several DIC scoring systems, neither fibrinogen, FDP, nor D-dimer was routinely measured.

BACKGROUND: Tick-borne infections, including tsutsugamushi disease, Japanese spotted fever, and severe fever with thrombocytopenia syndrome (SFTS), are prevalent in East Asia with varying geographic distribution and seasonality. This study aimed to investigate the differences in the characteristics among endemic areas for contracting each infection. METHODS: We conducted an ecologic study in Japan, using data from a nationwide inpatient database and publicly available geospatial data. We identified 4493 patients who were hospitalized for tick-borne infections between July 2010 and March 2021. Mixed-effects modified Poisson regression analysis was used to identify factors associated with a higher risk of contracting each tick-borne disease (Tsutsugamushi, Japanese spotted fever, and SFTS). RESULTS: Mixed-effects modified Poisson regression analysis revealed that environmental factors, such as temperature, sunlight duration, elevation, precipitation, and vegetation, were associated with the risk of contracting these diseases. Tsutsugamushi disease was positively associated with higher temperatures, farms, and forests, whereas Japanese spotted fever and SFTS were positively associated with higher solar radiation and forests. CONCLUSIONS: Our findings from this ecologic study indicate that different environmental factors play a significant role in the risk of transmission of tick-borne infections. Understanding the differences can aid in identifying high-risk areas and developing public health strategies for infection prevention. Further research is needed to address causal relationships.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals. METHODS: This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures. RESULTS: Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99-8.76), 7.27 (1.61-12.9), and 13.12 (3.48-22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality. CONCLUSIONS: The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities. Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450.

BACKGROUND: Although several clinical guidelines recommend vasodilator therapy for non-occlusive mesenteric ischemia (NOMI) and immediate surgery when bowel necrosis is suspected, these recommendations are based on limited evidence. METHODS: In this retrospective nationwide observational study, we used information from the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018 to identify patients with NOMI who underwent abdominal surgeries on the day of admission. We compared patients who received postoperative vasodilator therapy (vasodilator group) with those who did not (control group). Vasodilator therapy was defined as venous and/or arterial administration of papaverine and/or prostaglandin E1 within 2 days of admission. The primary outcome was in-hospital mortality. Secondary outcomes included the prevalence of additional abdominal surgery performed ≥3 days after admission and short bowel syndrome. RESULTS: We identified 928 eligible patients (149 in the vasodilator group and 779 in the control group). One-to-four propensity score matching yielded 149 and 596 patients for the vasodilator and control groups, respectively. There was no significant difference in in-hospital mortality between the groups (control vs. vasodilator, 27.5% vs. 30.9%; risk difference, 3.4%; 95% confidence interval, -4.9 to 11.6; p=0.42) and no significant difference in the prevalences of abdominal surgery, bowel resection ≥3 days after admission, and short bowel syndrome. CONCLUSIONS: Postoperative vasodilator use was not significantly associated with a reduction in in-hospital mortality or additional abdominal surgery performed ≥3 days after admission in surgically treated NOMI patients.

BACKGROUND: Ischemic heart disease is a leading cause of death worldwide, and coronary artery bypass grafting (CABG) is a major treatment. Landiolol is an ultra-short-acting beta-antagonist known to prevent postoperative atrial fibrillation. However, the effectiveness of intraoperative landiolol on mortality remains unknown. This study aimed to evaluate the association between intraoperative landiolol use and the in-hospital mortality in patients undergoing CABG. METHODS: To conduct this retrospective cohort study, we used data from the Japanese Diagnosis Procedure Combination inpatient database. All patients who underwent CABG during hospitalization between July 1, 2010, and March 31, 2020, were included. Patients who received intraoperative landiolol were defined as the landiolol group, whereas the other patients were defined as the control group. The primary outcome was in-hospital mortality. Propensity score matching was used to compare the landiolol and control groups. RESULTS: In total, 118,506 patients were eligible for this study, including 25,219 (21%) in the landiolol group and 93,287 (79%) in the control group. One-to-one propensity score matching created 24,893 pairs. After propensity score matching, the in-hospital mortality was significantly lower in the landiolol group than that in the control group (3.7% vs 4.3%; odds ratio 0.85; 95% confidence interval 0.78 to 0.94; P = .010). CONCLUSIONS: Intraoperative landiolol use was associated with decreased in-hospital mortality in patients undergoing CABG. Further randomized controlled trials are required to confirm these findings.

BACKGROUND: Perioperative discontinuation of oral anti-parkinsonian medication can negatively impact the prognosis of abdominal surgery in patients with Parkinson's disease. Although intravenous levodopa may be an alternative, its efficacy has not yet been investigated. OBJECTIVES: To determine the efficacy of intravenous levodopa as an alternative to oral anti-Parkinsonian drugs during gastric or colorectal cancer surgery. METHODS: We identified patients with Parkinson's disease who underwent surgery for gastric or colorectal cancer between April 2010 and March 2020, using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. Patients were divided into two groups: those who received intravenous levodopa during the perioperative period and those who did not. We compared in-hospital mortalities, major complications, and postoperative length of stay between the groups after adjusting for background characteristics with overlap weights based on propensity scores. RESULTS: We identified 648 patients who received intravenous levodopa and 1207 who did not receive levodopa during the perioperative period. In the adjusted cohort, the mean postoperative length of stay was 24.7 and 29.0 days (percent difference, -7.7%; 95% confidence interval, -13.1 to -1.5); in-hospital death was 3.2% and 3.3% (adjusted odds ratio, 0.95; 95% CI: 0.54-1.67); and incidence of major complications were 21.4% and 19.3% (adjusted odds ratio, 0.89; 95% confidence interval, 0.70-1.13) in those with and without intravenous levodopa, respectively. CONCLUSIONS: Intravenous levodopa was associated with a shorter postoperative length of stay, but not with mortality or morbidity. Intravenous levodopa may improve perioperative care in patients with Parkinson's disease.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

BACKGROUND: Ischemic heart disease is a leading cause of death worldwide, and coronary artery bypass grafting (CABG) is a major treatment. Landiolol is an ultra-short-acting beta-antagonist known to prevent postoperative atrial fibrillation. However, the effectiveness of intraoperative landiolol on mortality remains unknown. This study aimed to evaluate the association between intraoperative landiolol use and the in-hospital mortality in patients undergoing CABG. METHODS: To conduct this retrospective cohort study, we used data from the Japanese Diagnosis Procedure Combination inpatient database. All patients who underwent CABG during hospitalization between July 1, 2010, and March 31, 2020, were included. Patients who received intraoperative landiolol were defined as the landiolol group, whereas the other patients were defined as the control group. The primary outcome was in-hospital mortality. Propensity score matching was used to compare the landiolol and control groups. RESULTS: In total, 118,506 patients were eligible for this study, including 25,219 (21%) in the landiolol group and 93,287 (79%) in the control group. One-to-one propensity score matching created 24,893 pairs. After propensity score matching, the in-hospital mortality was significantly lower in the landiolol group than that in the control group (3.7% vs 4.3%; odds ratio 0.85; 95% confidence interval 0.78 to 0.94; P = .010). CONCLUSIONS: Intraoperative landiolol use was associated with decreased in-hospital mortality in patients undergoing CABG. Further randomized controlled trials are required to confirm these findings.

BACKGROUND: Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database. METHOD: We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested. RESULTS: A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend < 0.001). The FFP-to-RBC ratio rose significantly from 0.77 in 2011 to 1.08 in 2020 (P for trend < 0.001), while the platelet-to-RBC ratio remained virtually unchanged from 0.71 in 2011 to 0.78 in 2020 (P for trend 0.060). Massive transfusion with lower FFP-to-RBC (< 0.75) and platelets-to-RBC ratio (< 1.00) were associated with increased in-hospital mortality compared with those ≥ 1.00, while there were linear increases in adverse events with increasing FFP and platelets ratios. CONCLUSIONS: This study demonstrated a declining trend in the incidence and a rise in higher FFP-to-RBC ratios in massive transfusion in association with patient outcomes for trauma from 2011 to 2020 in Japan.

INTRODUCTION: Days of antibiotic spectrum coverage (DASC), a novel metric for both antimicrobial volume and spectrum, was proposed to measure inpatient antimicrobial consumption in 2022. The DASC may better reflect efforts toward antimicrobial stewardship; however, no previous study has described the distribution of trends in DASC in hospitals or the association between the trend in DASC and days of therapy (DOT). This study assessed trends in antimicrobial consumption for inpatients at acute care hospitals in Japan using the DOT and DASC. METHODS: This retrospective observational study used the nationwide administrative inpatient claims database of Japanese acute care hospitals between 2014 and 2018. The prescriptions of all antibiotics were identified to calculate DOT/1000 patient-days, DASC/1000 patient-days, and DASC/DOT. We described the five-year trend in these metrics and examined the association between the trends in DOT and DASC. RESULTS: In total, 26,301,685 admissions from 634 hospitals were included. The DOT/1000 patient-days and DASC/1000 patient-days increased significantly by 6.1% and 5.6%, respectively. The DASC/DOT ratio did not change significantly (P = 0.35). Moreover, there was little correlation between DOT/1000 patient-days and DASC/DOT (R2 = 0.01). There was also little correlation between the five-year changes in DOT/1000 patient-days and those in DASC/DOT (R2 = 0.02). CONCLUSIONS: It may be difficult to assess trends in the antibiotic spectrum using DASC alone. However, the combination of DOT as a quantity indicator and DASC/DOT as a spectrum indicator may allow for a more appropriate evaluation of stewardship efforts.

BACKGROUND: Palliative care provided to patients with heart failure (HF) are reported to be inadequate. Herein, we examined the impact of the recently introduced financial incentive scheme for team-based palliative care for patients with HF in acute care hospitals in Japan. METHODS: Using a nationwide inpatient database, we identified patients aged ≥65 years with HF who had died between April 2015 and March 2021. Interrupted time-series analyses were used to compare practice patterns in end-of-life care (symptom management and invasive medical procedures within one week before death) before and after the financial incentive scheme issuance in April 2018. RESULTS: Overall, 53,857 patients in 835 hospitals were eligible. The adoption of the financial incentive was 1.10 to 1.22% after the introduction. There were upward pre-trends in opioid use (+0.11% per month; 95% confidence interval [CI], 0.06 to 0.15) and antidepressant use (+0.06% per month; 95% CI, 0.04 to 0.09). Opioid use showed a downward slope change during the post-period (-0.07% change in trend; 95% CI, -0.13 to -0.01). Intensive care unit stay showed a downward pre-trend (-0.09% per month; 95% CI, -0.14 to -0.04) and upward slope changes during the post-period (+0.12% change in trend; 95% CI, 0.04 to 0.19). Invasive mechanical ventilation showed downward slope changes during the post-period (-0.11% change in trend; 95% CI, -0.18 to -0.04). CONCLUSIONS: The financial incentive scheme for team-based palliative care was rarely adopted and not associated with changes in end-of-life care. Further multifaceted strategies to promote palliative care for HF are warranted.

Little is known about the impact of the downgrade of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella in Japan, where IABPs have been predominantly used. This study aimed to describe the annual trends in the mechanical circulatory support (MCS) use and outcomes in patients with cardiogenic shock (CS) requiring MCS. Using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2021, we identified inpatients with CS requiring MCS. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella alone, and (3) extracorporeal membrane oxygenation (ECMO), regardless of IABP or Impella use. The patient characteristics and outcomes were reported by the fiscal year. Of the 160,559 eligible patients, 117,599 (73.2%) used IABP alone, 1,465 (0.9%) Impella alone, and 41,495 (25.8%) ECMO. The prevalence of the use of an IABP alone significantly decreased from 80.5% in 2010 to 65.3% in 2020 (p for trend <0.001), whereas the prevalence of the use of an Impella alone significantly increased from 0.0% to 5.0% and ECMO from 19.5% to 29.6% (p for trend <0.001 for both). In-hospital mortality significantly increased from 29.3% in 2010 to 32.6% in 2020 in the overall patients with CS requiring MCS but significantly decreased in those requiring ECMO from 73.7% to 64.1% (p for trend <0.001 for both). In conclusion, there were significant annual changes in the patterns of MCS use and clinical outcomes in patients with CS requiring MCS.

OBJECTIVES: To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC). METHODS: This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within two days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or hemodialysis dependence at discharge. RESULTS: Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs. 49.0%; odds ratio, 0.69; 95% confidence interval, 0.48-1.00; P= 0.049). CONCLUSIONS: The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or hemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings.

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high-risk PE were defined as those admitted for out-of-hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non-high-risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high-risk PE, and the remaining 80 850 (90.9%) had non-high-risk PE. Between 2010 and 2020, in patients with high-risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 51.0% to 43.7% (P for trend=0.04). In patients with non-high-risk PE, the annual proportion of direct oral anticoagulant use increased from 0.0% to 38.3%, whereas that of thrombolysis use significantly decreased from 13.7% to 3.4% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 7.9% to 5.4% (P for trend <0.001). Conclusions Substantial changes in the PE practice and outcomes occurred in patients with high-risk and non-high-risk PE.

BACKGROUND: Preoperative stoma site marking reduces the incidence of complications from elective surgery. However, the impact of stoma site marking in emergency patients with colorectal perforation remains unclear. This study aimed to assess the impact of stoma site marking on morbidity and mortality in patients with colorectal perforation who underwent emergency surgery. METHODS: This retrospective cohort study used the Japanese Diagnosis Procedure Combination inpatient database from April 1, 2012, to March 31, 2020. We identified patients who underwent emergency surgery for colorectal perforation. We compared outcomes between those with and without stoma site marking using propensity score matching to adjust for confounding factors. The primary outcome was the overall complication rate, and the secondary outcomes were stoma-related, surgical, and medical complications and 30-day mortality. RESULTS: We identified 21,153 patients (682 with stoma site marking and 20,471 without stoma site marking) and grouped them into 682 pairs using propensity score matching. The overall complication rates were 23.5% and 21.4% in the groups with and without stoma site marking, respectively (p = 0.40). Stoma site marking was not associated with a decrease in stoma-related, surgical, or medical complications. The 30-day mortality did not differ significantly between the groups with and without stoma site marking (7.9% vs. 8.4%, p = 0.843). CONCLUSIONS: Preoperative stoma site marking was not associated with a reduction in morbidity and mortality in patients with colorectal perforation who underwent emergency surgery.

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) is a serious condition after critical care. We examined the efficacy of antithrombin, which may attenuate coagulopathy with the control of inflammation, for PICS among patients with sepsis-induced disseminated intravascular coagulation (DIC). The present study used the inpatient claims database with laboratory findings to identify patients admitted to intensive care units and diagnosed with sepsis and DIC. A composite of the incidence of PICS on day 14 or 14-day mortality as the primary outcome was compared between the antithrombin and control groups using a propensity-score-matched analysis. Secondary outcomes were the incidence of PICS on day 28, 28-day mortality, and in-hospital mortality. A total of 324 well-balanced matched pairs were generated from 1622 patients. The primary outcome did not differ between the antithrombin and control groups (63.9% vs. 68.2%, respectively, p = 0.245). However, the incidences of 28-day and in-hospital mortality were significantly lower in the antithrombin group (16.0% vs. 23.5% and 24.4% vs. 35.8%, respectively). Similar results were obtained in a sensitivity analysis using overlap weighting. Antithrombin did not reduce the occurrence of PICS on day 14 in patients with sepsis-induced DIC; however, it was associated with a better mid-term (day 28) prognosis.

OBJECTIVE: To investigate the 1-year functional outcomes after cardiopulmonary resuscitation (CPR) in adults aged ≥65 years with pre-existing long-term care needs. METHODS: This population-based cohort study was conducted in Tochigi Prefecture, one of 47 prefectures in Japan. We used medical and long-term care administrative databases, which included data on functional and cognitive impairment that were assessed with the nationally standardised care-needs certification system. Among individuals aged ≥65 years registered between June 2014 and February 2018, patients who underwent CPR were identified. The primary outcome was mortality and care needs at 1 year after CPR. The outcome was stratified by pre-existing care needs before CPR based on the total daily estimated care minutes: no care needs, support levels 1 and 2 and care-needs level 1 (estimated care time 25-49 min), care-needs levels 2 and 3 (50-89 min) and care-needs levels 4 and 5 (≥90 min). RESULTS: Among 594,092 eligible individuals, 5,086 (0.9%) underwent CPR. The 1-year mortalities after CPR in patients with no care needs, support levels 1 and 2 and care-needs level 1, care-needs levels 2 and 3 and care-needs levels 4 and 5 were 94.6% (n = 2,207/2,332), 96.1% (n = 736/766), 94.5% (n = 930/984) and 95.9% (n = 963/1,004), respectively. Among survivors, most patients had no change in care needs before and at 1 year after CPR. There was no significant association between pre-existing functional and cognitive impairment and 1-year mortality and care needs after adjusting for potential confounders. CONCLUSION: Healthcare providers need to discuss poor survival outcomes after CPR with all older adults and their families in shared decision making.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus. Effective treatment for SFTS has not been established, but steroid pulse therapy is often used. This study aimed to verify whether steroid pulse therapy for SFTS improves prognosis or not. METHODS: Data of SFTS patients were obtained from the Japanese Diagnosis Procedure Combination Database from April 2013 to March 2021. Patients treated with steroid pulse therapy were compared with untreated patients, using overlap weighting and traditional multivariable regression analysis to evaluate the impact of steroid pulse therapy on prognosis. RESULTS: 412 SFTS patients were included in this study, and 66 (16%) underwent steroid pulse therapy within 3 days of admission and were allocated to the steroid pulse therapy group. After overlap weighting, patients in the steroid pulse therapy group had a significantly higher in-hospital mortality rate than patients in the control group (31.1% vs. 20.5%; difference: +10.6%; 95% confidence interval: +2.2% to +19.0%). There were no statistically significant differences in hospitalization cost and length of hospital stay between the two groups. The results of the sensitivity analysis using traditional multivariable regression were similar to those of the main analysis. CONCLUSION: In the analysis of SFTS patients using the Japanese Diagnosis Procedure Combination inpatient data, steroid pulse therapy did not improve patient prognosis. The evidence does not support the universal use of steroid pulse therapy in patients with severe SFTS.

The present study aimed to investigate the appropriate timing of excision or skin grafting of burn wounds in patients with severe burns. We retrospectively analyzed data from the Diagnosis Procedure Combination Database, a nationwide inpatient database in Japan. Patients with severe burns (burn index ≥10) who underwent excision or skin grafting within 7 days from September 2010 to March 2019 were included. We defined the early surgery group as patients who underwent excision or skin grafting within 2 days of admission and the delayed surgery group as those who underwent surgery within 3-7 days of admission. Propensity score matching was used to compare the in-hospital mortality between the two groups, yielding a cohort of 389 pairs. A total of 2362 eligible patients were categorized into the early surgery group (n = 626) and delayed surgery group (n = 1736). The overall in-hospital mortality was 19.6%. In-hospital mortality did not differ significantly between the early surgery (15.9%) and the delayed surgery groups (17.2%; p = 0.70). These results suggest that excision or skin grafting within 2 days of admission was not associated with improved in-hospital mortality compared with surgery thereafter for patients with severe burns.

OBJECTIVES: To assess the association between levels of intensive care and in-hospital mortality in patients hospitalized for sepsis, stratified by Sequential Organ Failure Assessment (SOFA) score at admission. DESIGN: A nationwide, propensity score-matched, retrospective cohort study. SETTING: A Japanese national inpatient database with data on 70-75% of all ICU and high-dependency care unit (HDU) beds in Japan. PATIENTS: Adult patients hospitalized for sepsis with SOFA scores greater than or equal to 2 on their day of admission between April 1, 2018, and March 31, 2021, were recruited. Propensity score matching was performed to compare in-hospital mortality, and patients were stratified into 10 groups according eto SOFA scores. INTERVENTIONS: Two exposure and control groups according to treatment unit on day of admission: 1) ICU + HDU versus general ward and 2) ICU versus HDU. MEASUREMENTS AND MAIN RESULTS: Of 97,070 patients, 19,770 (20.4%), 23,066 (23.8%), and 54,234 (55.9%) were treated in ICU, HDU, and general ward, respectively. After propensity score matching, the ICU + HDU group had significantly lower in-hospital mortality than the general ward group, among cohorts with SOFA scores greater than or equal to 6. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 3-5. The ICU + HDU group had significantly higher in-hospital mortality than the general ward among cohorts with SOFA scores of 2. The ICU group had lower in-hospital mortality than the HDU group among cohorts with SOFA scores greater than or equal to 12. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 5-11. The ICU group had significantly higher in-hospital mortality than the general ward group among cohorts with SOFA scores less than or equal to 4. CONCLUSIONS: Patients hospitalized for sepsis with SOFA scores greater than or equal to 6 in the ICU or HDU had lower in-hospital mortality than those in the general ward, as did those with SOFA scores greater than or equal to 12 in the ICU versus HDU.

BACKGROUND: This study aimed to evaluate the effects of medical fee revisions aimed to reduce psychotropic polypharmacy in Japan on the proportion of psychotropic polypharmacy in discharge prescriptions for patients with major depressive disorder (MDD) or bipolar disorder (BD) using a nationwide inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database to identify patients with MDD or BD discharged between April 2012 and March 2021. We targeted medical fee revisions in October 2014, April 2016, and April 2018. The major outcome was the monthly proportion of psychotropic polypharmacy in prescription at discharge using the criteria following the April 2018 revision (antidepressants ≥3, antipsychotics ≥3, anxiolytics ≥3, hypnotics ≥3, or sum of anxiolytics and hypnotics ≥4). We performed interrupted time series analyses to evaluate the changes in level and trend between pre- and post-revisions. RESULTS: We identified 63,289 and 33,780 patients with MDD and BD respectively in the entire study period. In both the patient groups, there were significant decreases in the proportion of psychotropic polypharmacy at revision in October 2014, and no significant trend and level change at revision were observed in April 2016 and April 2018, with a few exceptions. CONCLUSIONS: The medical fee revisions aimed to reduce psychotropic polypharmacy in Japan might have had a limited impact on discharge prescriptions for patients with MDD and BD.

BACKGROUND: The optimal surgical procedure to reduce the recurrence rate of chronic subdural hematoma (CSDH) after burr-hole surgery remains to be established. This study aimed to investigate the association between artificial cerebrospinal fluid (ACF) use during burr-hole surgery and reoperation rate in patients with CSDH. METHOD: In this retrospective cohort study, we used the Japanese Diagnostic Procedure Combination inpatient database. We identified patients aged 40-90 years who were hospitalized for CSDH and had undergone burr-hole surgery within 2 days of admission, between July 1, 2010 and March 31, 2019. We performed a one-to-one propensity score-matched analysis to compare the outcomes between patients with and without ACF irrigation during burr-hole surgery. The primary outcome was reoperation within 1 year of surgery. The secondary outcome was the total hospitalization costs. RESULTS: Of the 149,543 patients with CSDH from 1100 hospitals, ACF was used in 32,748 patients (21.9%). Propensity score matching created highly balanced 13,894 matched pairs. In the matched patients, the reoperation rate was significantly lower in the ACF users than that in the non-users group (6.3% vs. 7.0%, P = 0.015), with a risk difference of -0.8% (95% confidence interval, -1.5 to -0.2). There was no significant difference in the total hospitalization costs between the two groups (5079 vs. 5042 US dollars, P = 0.330). CONCLUSIONS: ACF use during burr-hole surgery may be associated with lower reoperation rate in patients with CSDH.

IMPORTANCE: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse reactions, and patients with SJS/TEN frequently require intensive care. However, there is limited evidence on the clinical outcomes of immunomodulating therapy, including plasmapheresis and intravenous immunoglobulin (IVIG) in patients with SJS/TEN. OBJECTIVE: To compare clinical outcomes of patients with SJS/TEN who were treated with plasmapheresis first vs IVIG first after ineffective systemic corticosteroid therapy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from a national administrative claims database in Japan that included more than 1200 hospitals and was conducted from July 2010 to March 2019. Inpatients with SJS/TEN who received plasmapheresis and/or IVIG therapy after initiation of at least 1000 mg/d of methylprednisolone equivalent systemic corticosteroid therapy within 3 days of hospitalization were included. Data were analyzed from October 2020 to May 2021. EXPOSURES: Patients who received IVIG or plasmapheresis therapy within 5 days after initiation of systemic corticosteroid therapy were included in the IVIG- and plasmapheresis-first groups, respectively. MAIN OUTCOMES AND MEASURES: In-hospital mortality, length of hospital stay, and medical costs. RESULTS: Of 1215 patients with SJS/TEN who had received at least 1000 mg/d of methylprednisolone equivalent within 3 days of hospitalization, 53 and 213 patients (mean [SD] age, 56.7 [20.2] years; 152 [57.1%] women) were included in the plasmapheresis- and IVIG-first groups, respectively. Propensity-score overlap weighting showed no significant difference in inpatient mortality rates between the plasmapheresis- and IVIG-first groups (18.3% vs 19.5%; odds ratio, 0.93; 95% CI, 0.38-2.23; P = .86). Compared with the IVIG-first group, the plasmapheresis-first group had a longer hospital stay (45.3 vs 32.8 days; difference, 12.5 days; 95% CI, 0.4-24.5 d; P = .04) and higher medical costs (US $34 262 vs $23 054; difference, US $11 207; 95% CI, $2789-$19 626; P = .009). CONCLUSIONS AND RELEVANCE: This nationwide retrospective cohort study found no significant benefit to administering plasmapheresis therapy first instead of IVIG first after ineffective systemic corticosteroid treatment in patients with SJS/TEN. However, medical costs and length of hospital stay were greater for the plasmapheresis-first group.

OBJECTIVES: To examine 1-year functional outcomes after invasive mechanical ventilation for adults greater than or equal to 65 years with preexisting long-term care-needs. DESIGN: We used medical and long-term care administrative databases. The database included data on functional and cognitive impairments that were assessed with the national standardized care-needs certification system and were categorized into seven care-needs levels based on the total daily estimated care minutes. Primary outcome was mortality and care-needs at 1 year after invasive mechanical ventilation. Outcome was stratified by preexisting care-needs at the time of invasive mechanical ventilation: no care-needs, support level 1-2 and care-needs level 1 (estimated care time 25-49 min), care-needs level 2-3 (50-89 min), and care-needs level 4-5 (≥90 min). SETTING: A population-based cohort study in Tochigi Prefecture, one of 47 prefectures in Japan. PATIENTS: Among people greater than or equal to 65 years old registered between June 2014 and February 2018, patients who received invasive mechanical ventilation were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 593,990 eligible people, 4,198 (0.7%) received invasive mechanical ventilation. The mean age was 81.2 years, and 55.5% were male. The 1-year mortality rates after invasive mechanical ventilation in patients with no care-needs, support level 1-2 and care-needs level 1, care-needs level 2-3, and care-needs level 4-5 at the time of invasive mechanical ventilation were 43.4%, 54.9%, 67.8%, and 74.1%, respectively. Similarly, those with worsened care-needs were 22.8%, 24.2%, 11.4%, and 1.9%, respectively. CONCLUSIONS: Among patients in preexisting care-needs levels 2-5 who received invasive mechanical ventilation, 76.0-79.2% died or had worsened care-needs within 1 year. These findings may aid shared decision-making among patients, their families, and heath care professionals on the appropriateness of starting invasive mechanical ventilation for people with poor functional and cognitive status at baseline.

BACKGROUND: Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present with cardiogenic shock but do not require venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring VA-ECMO. We aimed to evaluate whether systemic thrombolysis improved high-risk PE patients' outcomes who received VA-ECMO. METHODS: This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. We identified patients who were diagnosed with PE and received VA-ECMO on the day of admission. Patients who received systemic thrombolysis with monteplase or urokinase within two days of initiating VA-ECMO were defined as the thrombolysis group and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favorable neurological outcomes, length of hospital stay, VA-ECMO duration, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups. RESULTS: Of 1220 eligible patients, 432 (35%) received systemic thrombolysis within two days of initiating VA-ECMO. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 61% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: - 3.0%, 95% confidence interval: - 9.6% to 3.5%). There were also no significant differences in the secondary outcomes. Sensitivity analyses showed a significant difference in major bleeding between the monteplase and control groups (risk difference: 6.9%, 95% confidence interval: 1.7% to 12.1%), excluding patients who received urokinase. There were no significant differences in the other sensitivity and subgroup analyses except for the total hospitalization cost. CONCLUSIONS: Systemic thrombolysis was not associated with reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving VA-ECMO. However, systemic thrombolysis with monteplase was associated with increased major bleeding.

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD.

OBJECTIVE: Adjuvant medical treatment to reduce the recurrence rate after burr hole surgery for chronic subdural hematoma (CSDH) has not yet been established. This study aimed to investigate the association between tranexamic acid (TXA) use after burr hole surgery and the reoperation rate in patients with CSDH. METHODS: This observational study used the Japanese Diagnostic Procedure Combination inpatient database, a nationwide inpatient database in Japan, from July 1, 2010, to March 31, 2019. The authors identified patients who were hospitalized for CSDH and underwent burr hole surgery within 2 days of admission. The primary outcome measure was reoperation within 1 year after surgery. One-to-one propensity score-matched analysis was performed to compare the outcomes between patients who started oral TXA within 2 days after surgery (TXA users) and those who did not (TXA nonusers). Robustness of the analyses was assessed using the instrumental variable analysis. RESULTS: Of the 149,543 patients with CSDH treated at 1100 hospitals, 7366 (4.9%) were TXA users. Propensity score matching created 6564 matched pairs with highly balanced baseline characteristics. The reoperation rate was significantly lower in TXA users than in nonusers (1.9% vs 6.1%, p < 0.001) with a risk difference of -4.1% (95% CI -4.8% to -3.4%). There was no significant difference in composite adverse events (0.6% vs 0.5%, p = 0.817). Total hospitalization costs were also significantly lower in TXA users than in nonusers ($5229 vs $5344 [USD], p < 0.001). The results of the instrumental variable analysis were consistent with those of the propensity score-matched analysis. CONCLUSIONS: Findings of this study, using a nationwide inpatient database, suggest that adjuvant TXA use after burr hole surgery was associated with a reduced reoperation rate in patients with CSDH.

BACKGROUND: The acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has cytokine adsorption capacity and is used for treating sepsis. This study aimed to compare the effects of continuous renal replacement therapy (CRRT) using the AN69ST membrane with those of CRRT using other membranes for patients with pneumonia-associated sepsis. METHODS: This retrospective, propensity score-matched, cohort study was based on a nationwide Japanese inpatient database. We included data from adults hospitalized with a primary diagnosis of pneumonia, who received CRRT using either the AN69ST membrane or another membrane within 2 days of admission, and who were discharged from the hospitals between September 2014, and March 2017. Propensity score matching was used to compare in-hospital mortality between the two groups. RESULTS: Eligible patients (N = 2393) were categorized into an AN69ST group (N = 631) and a non-AN69ST group (N = 1762). The overall in-hospital mortality rate was 38.9%. Among the 545 propensity-matched patient pairs, the in-hospital mortality rate was significantly lower in the AN69ST group than in the non-AN69ST group (35.8 vs. 41.8%, p = 0.046). CONCLUSIONS: Among patients with pneumonia-associated sepsis treated with CRRT, CRRT with the AN69ST membrane was associated with a significantly lower in-hospital mortality than CRRT with standard membranes.

PURPOSE: This study aimed to develop an ancestry-specific polygenic risk scores (PRSs) for the prediction of breast cancer events in Japanese females and validate it in a longitudinal cohort study. METHODS: Using publicly available summary statistics of female breast cancer genome-wide association study (GWAS) of Japanese and European ancestries, we, respectively, developed 31 candidate genome-wide PRSs using pruning and thresholding (P + T) and LDpred methods with varying parameters. Among the candidate PRS models, the best model was selected using a case-cohort dataset (63 breast cancer cases and 2213 sub-cohorts of Japanese females during a median follow-up of 11.9 years) according to the maximal predictive ability by Harrell's C-statistics. The best-performing PRS for each derivation GWAS was evaluated in another independent case-cohort dataset (260 breast cancer cases and 7845 sub-cohorts of Japanese females during a median follow-up of 16.9 years). RESULTS: For the best PRS model involving 46,861 single nucleotide polymorphisms (SNPs; P + T method with PT = 0.05 and R2 = 0.2) derived from Japanese-ancestry GWAS, the Harrell's C-statistic was 0.598 ± 0.018 in the evaluation dataset. The age-adjusted hazard ratio for breast cancer in females with the highest PRS quintile compared with those in the lowest PRS quintile was 2.47 (95% confidence intervals, 1.64-3.70). The PRS constructed using Japanese-ancestry GWAS demonstrated better predictive performance for breast cancer in Japanese females than that using European-ancestry GWAS (Harrell's C-statistics 0.598 versus 0.586). CONCLUSION: This study developed a breast cancer PRS for Japanese females and demonstrated the usefulness of the PRS for breast cancer risk stratification.

AIM: Hypoglycemia at admission is associated with high mortality in sepsis patients. However, the influence of body mass index (BMI) on this association remains unknown. Therefore, this study assesses the association of hypoglycemia at admission with mortality in patients with sepsis according to BMI. METHODS: This was a secondary analysis of a multicenter, prospective cohort study of 59 intensive care units in Japan. We included 1184 patients (age ≥16 years) with severe sepsis and excluded those with missing data on glucose level, BMI, or survival at discharge. The initial blood glucose level of <70 mg/dL was defined as hypoglycemia. Patients were assigned to the hypoglycemia or non-hypoglycemia group as per BMI category (<18.5 [low], 18.5-24.9 [normal], and ≥25 [high] kg/m2). The main outcome was in-hospital mortality. Multivariate logistic regression models were used to evaluate BMI category-by-hypoglycemia interactions. RESULTS: Overall, 1103 patients, including 65 with hypoglycemia, were analyzed. In the normal BMI group, patients with hypoglycemia had a higher in-hospital mortality rate (18/38, 47.4%) than those without (119/584, 20.4%). There was a significant interaction between normal BMI and hypoglycemia affecting in-hospital mortality; however, this effect was not observed for other BMI categories (odds ratio, 2.32; 95% confidence interval, 1.05-5.07; p-value for interaction = 0.0476). CONCLUSION: The relationship between patients with sepsis and hypoglycemia on admission may differ according to BMI. Hypoglycemia on admission may be associated with high mortality in patients with normal BMI, but not in those with low or high BMI.

Rationale: High-dependency care units (HDUs), also termed "intermediate care units", "step-down units", or "respiratory HDUs", are areas in which degrees of patient care and costs are between those of the intensive care unit (ICU) and the general ward. In general, patients requiring mechanical ventilation are treated in the ICU rather than in the HDU, except for the use of HDU beds as surge capacity beds during a massive strain; however, the HDU, as well as ICU, are used as the standard care units for mechanically ventilated patients with coronavirus disease (COVID-19) in Japan. Objectives: To assess the outcomes of patients with COVID-19 with invasive mechanical ventilation treated in the HDU versus those treated in the ICU. Methods: In this retrospective cohort study, we used a multicenter inpatient database in Japan to identify mechanically ventilated patients with COVID-19 in the ICU or HDU on the start day of invasive mechanical ventilation from February 10, 2020, to November 30, 2021. The primary outcome was in-hospital mortality within 30 days from the start of the first invasive mechanical ventilation. Propensity score matching was performed to compare the outcomes of patients treated in the ICU with those treated in the HDU. Results: Of 1,985 eligible patients with COVID-19 with invasive mechanical ventilation, 1,303 (66%) were treated in the ICU, and 682 (34%) were treated in the HDU on the start day of invasive mechanical ventilation. After propensity score matching, patients treated in the ICU had significantly lower in-hospital mortality within 30 days than those treated in the HDU (18.3% vs. 24.2%; risk difference, -5.8%; 95% confidence interval, -10.9% to -0.8%). Conclusions: This multicenter observational study in Japan suggests that care for mechanically ventilated patients with COVID-19 in the ICU may significantly reduce in-hospital mortality within 30 days compared with care in the HDU. Establishing a critical care system that would allow patients with COVID-19 requiring ventilators to be treated in the ICU is desirable. Because this study was an observational study, our finding represents an association, not causation. Further studies of different critical care systems are warranted to confirm our findings.

BACKGROUND: The optimal timing of antibiotic administration in patients with a liver abscess undergoing liver aspiration or drainage is unknown. METHODS: This was a retrospective cohort study using the Diagnosis Procedure Combination database, a national inpatient database in Japan. RESULTS: A total of 34,424 patients who were emergently hospitalized due to liver abscess between July 2010 and March 2020 were included. Of these, 31,248 (90.8%) received antibiotics on the day of admission (early antibiotics group), and 3176 (9.2%) did not (delayed antibiotics group). Multivariable logistic regression analyses showed that in-hospital mortality of patients in the early antibiotics group was significantly lower than that in the delayed antibiotics group (odds ratio, 0.61; 95% confidence interval, 0.52-0.72; p <0.001). Patients in the early antibiotics group had a significantly lower proportion of clinical deterioration (odds ratio, 0.73; 95% confidence interval, 0.63-0.84; p <0.001) and shorter length of stay (adjusted difference, -5.2 days; 95% confidence interval, -6.2 to -4.1 days; p <0.001) than those in the delayed antibiotics group. CONCLUSIONS: Starting antibiotic treatment on the day of admission was associated with lower mortality, a lower proportion of clinical deterioration, and a shorter length of hospital stay.

BACKGROUND: Detailed data on intensive care unit (ICU) occupancy in Japan are lacking. Using a nationwide inpatient database in Japan, we aimed to assess ICU bed occupancy to guide critical care utilization planning. METHODS: We identified all ICU patients admitted from January 1, 2015 to December 31, 2018 to ICU-equipped hospitals participating in the Japanese Diagnosis Procedure Combination inpatient database. We assessed the trends in daily occupancy by counting the total number of occupied ICU beds on a given day divided by the total number of licensed ICU beds in the participating hospitals. We also assessed ICU occupancy for patients with mechanical ventilation, patients with extracorporeal membrane oxygenation, and patients without life-supportive therapies. RESULTS: Over the 4 study years, 1,379,618 ICU patients were admitted to 495 hospitals equipped with 5,341 ICU beds, accounting for 75% of all ICU beds in Japan. Mean ICU occupancy on any given day was 60%, with a range of 45.0% to 72.5%. Mean ICU occupancy did not change over the 4 years. Mean ICU occupancy was about 9% higher on weekdays than on weekends and about 5% higher in the coldest season than in the warmest season. For patients with mechanical ventilation, patients with extracorporeal membrane oxygenation, and patients without life-supportive therapies, mean ICU occupancy was 24%, 0.5%, and 30%, respectively. CONCLUSION: Only one-fourth of ICU beds were occupied by mechanically ventilated patients, suggesting that the critical care system in Japan has substantial surge capacity under normal temporal variation to care for critically ill patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted critical care services worldwide. Examining how critical care systems responded to the COVID-19 pandemic on a national level will be useful in setting future critical care plans. The present study aimed to describe the utilization of critical care services before and during the COVID-19 pandemic using a nationwide Japanese inpatient administrative database. METHODS: All patients admitted to an intensive care unit (ICU) or a high-dependency care unit (HDU) from February 9, 2019, to February 8, 2021, in the Japanese Diagnosis Procedure Combination inpatient database were included. February 9, 2020, was used as the breakpoint separating the periods before and during COVID-19 pandemic. Hospital and patient characteristics were compared before and during the COVID-19 pandemic. Change in ICU and HDU bed occupancy before and during the COVID-19 pandemic was evaluated using interrupted time-series analysis. RESULTS: The number of ICU patients before and during the COVID-19 pandemic was 297,679 and 277,799, respectively, and the number of HDU patients was 408,005 and 384,647, respectively. In the participating hospitals (383 ICU-equipped hospitals and 460 HDU-equipped hospitals), the number of hospitals which increased the ICU and HDU beds capacity were 14 (3.7%) and 33 (7.2%), respectively. Patient characteristics and outcomes in ICU and HDU were similar before and during the COVID-19 pandemic except main etiology for admission of COVID-19. The mean ICU bed occupancy before and during the COVID-19 pandemic was 51.5% and 47.5%, respectively. The interrupted time-series analysis showed a downward level change in ICU bed occupancy during the COVID-19 pandemic (- 4.29%, 95% confidence intervals - 5.69 to - 2.88%), and HDU bed occupancy showed similar trends. Of 383 hospitals with ICUs, 232 (60.6%) treated COVID-19 patients in their ICUs. Their annual hospital case volume of COVID-19 ICU patients varied greatly, with a median of 10 (interquartile range 3-25, min 1, max 444). CONCLUSIONS: The ICU and HDU bed capacity did not increase while their bed occupancy decreased during the COVID-19 pandemic in Japan. There was no change in clinicians' decision-making to forego ICU/HDU care for selected patients, and there was no progress in the centralization of critically ill COVID-19 patients.

AIM: Several studies have reported that corticosteroid administration for cardiac arrest patients may improve outcomes. However, these previous studies have not examined the effect of corticosteroid use in out-of-hospital cardiac arrest (OHCA) patients administered extracorporeal cardiopulmonary resuscitation (ECPR). Therefore, we aimed to examine the effectiveness of corticosteroids in OHCA patients administered ECPR. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we included OHCA patients who were administered ECPR on the day of admission between July 2010 and March 2019. The patients were categorized into the corticosteroid and control groups according to whether they received corticosteroids on the day of admission or not. The primary outcome was in-hospital mortality and the secondary outcomes included percentages of neurologically favorable survival, major bleeding complications, and infection-related complications. We compared the outcomes using a propensity score matching analysis. RESULTS: We identified 6,142 eligible patients (459 vs 5,683, the corticosteroid and control group, respectively). One-to-four propensity score matching analysis (457 vs 1,827) showed in-hospital mortality was significantly higher in the corticosteroid group compared with the control group (82.1% vs 76.6%; risk difference, 5.5%; 95% CI, 1.5 to 9.5%). Neurologically favorable outcomes did not differ between the two groups (13.6% vs 16.9%; risk difference, -3.3%; 95% CI, -6.9 to 0.3%). The percentage of major bleeding complications and infection-related complications did not significantly differ between the two groups. CONCLUSIONS: The results of this study demonstrated that administration of corticosteroids on the day of admission to OHCA patients administered ECPR was associated with increased in-hospital mortality.

OBJECTIVES: Although existing guidelines recommend commencing cannulation for extracorporeal cardiopulmonary resuscitation (ECPR) within 10-20 minutes of failed conventional resuscitation efforts for cardiac arrest, there is little supportive evidence. The present study aimed to determine the association of low-flow duration with survival-to-discharge rate in in-hospital cardiac arrest patients who received ECPR. DESIGN: A nationwide retrospective cohort study analyzed a nationwide inpatient database in Japan. Low-flow duration was defined as the time interval from initiation of chest compression to termination of chest compression. We assessed the association between low-flow duration and survival-to-discharge rate by predicting estimates with covariate adjustment stratified by categories of low-flow duration. SETTING: More than 1,600 acute-care hospitals in Japan. PATIENTS: All in-hospital cardiac arrest patients greater than or equal to 18 years old who received ECPR during hospitalization from July 2010 to March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 303,319 in-hospital cardiac arrest patients, 9,844 (3.2%) received ECPR in 697 hospitals during the study period and 9,433 were eligible in the study. The overall survival-to-discharge rate was 20.5% (1,932/9,433). The median low-flow duration was 26.0 minutes (interquartile range, 12.0-46.0 min) in the overall cohort. The highest and lowest estimated survival-to-discharge rates were 35.1% in the group with low-flow duration 0-5 minutes and 7.9% in the group with low-flow duration greater than 90 minutes. The estimated survival-to-discharge rate dropped sharply by about 20% during the first 35 minutes of low-flow duration (decreasing by about 3% every 5 min), followed by small decreases after the first 35 minutes. CONCLUSIONS: The estimated survival-to-discharge rate was markedly decreased by approximately 20% during the first 35 minutes of low-flow duration. Whether we should wait for the first 10-20 minutes of cardiac arrest without preparing for ECPR is questionable.

OBJECTIVES: Current guidelines recommend colonoscopy within 24 h for acute lower gastrointestinal bleeding; however, the evidence in support for colonic diverticular hemorrhage (CDH) indications remains insufficient. We use a nationwide database to investigate the effectiveness of early colonoscopy for CDH. METHODS: We conducted a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database and identified patients who were admitted for CDH from 2010 to 2017. Patients who underwent colonoscopy on the same day of admission (early group) were compared with those who underwent colonoscopy on the next day of admission (elective group). The primary outcome was in-hospital mortality, and secondary outcomes were length of hospital stay, total hospitalization cost, fasting period, and the prevalence of re-colonoscopy, interventional radiology or abdominal surgery. Propensity score matching was used to adjust for confounders. RESULTS: We identified 74,569 eligible patients. Patients were divided into the early (n = 46,759) and elective (n = 27,810) groups. After propensity score matching, 27,696 pairs were generated. In-hospital mortality did not significantly differ between the two groups (0.49% in the early group vs. 0.41% in the elective group; risk difference 0.08%; 95% confidence interval -0.02 to 0.19; P = 0.14). The early group had a significantly longer length of hospital stay, higher total hospitalization cost, longer fasting period, and higher prevalence of re-colonoscopy and abdominal surgery. CONCLUSIONS: The effectiveness of early colonoscopy conducted on the same day of admission for CDH could not be confirmed. Early colonoscopy may not result in favorable outcomes in CDH patients.

BACKGROUND: This study aimed to determine the relationship between time to tetracycline therapy initiation and disease outcome in patients hospitalized with Japanese spotted fever (JSF). METHODS: Patients with JSF enrolled in the Japanese Diagnosis Procedure Combination database from July 2010 to March 2021 were included in the analysis. Patients who received tetracycline on the day of admission were compared with those who received tetracycline later during their hospital stay using inverse probability of treatment weighting. The primary outcome was in-hospital mortality. Secondary outcomes were total hospitalization cost and length of hospital stay. RESULTS: A total of 1360 patients were included, of whom 1060 (78%) received tetracycline on the day of admission (early tetracycline group), and 300 (22%) received tetracycline later (delayed tetracycline group). Patients in the delayed tetracycline group had significantly higher in-hospital mortality than those in the early tetracycline group (3.9% vs 1.4%; odds ratio, 2.94; 95% CI, 1.34-6.47), significantly higher hospitalization costs, and longer hospital stays than those in the early tetracycline group. CONCLUSIONS: The prognosis of patients with JSF is worse if tetracycline administration is delayed; therefore, physicians should initiate tetracycline on admission if JSF is suspected as a possible diagnosis.

The factors that prolong the on-site time in pediatric trauma cases in a prehospital setting are unknown. We investigated these factors using a national trauma registry in Japan. We identified pediatric trauma patients aged ≤18 years, from January 2004 to May 2019. We categorized cases into shorter (≤13 min) and longer (>13 min) prehospital on-site time groups. We performed multivariable logistic regression analysis with multiple imputations to assess the factors associated with longer prehospital on-site time. Overall, 14,535 patients qualified for inclusion. The median prehospital on-site time was 13 min. In the multivariable logistic regression analysis, the longer prehospital on-site time was associated with higher age; suicide (Odds ratio [OR] 1.27; 95% confidence interval [CI] 1.03−1.57); violence (OR 1.74; 95%CI 1.27−2.38); higher revised trauma score, abbreviated injury scale > 3 in the spine (OR 1.25; 95%CI 1.04−1.50), upper extremity (OR 1.26; 95%CI 1.11−1.44), and lower extremity (OR 1.25; 95%CI 1.14−1.37); immobilization (OR 1.16; 95%CI 1.06−1.27); and comorbid mental retardation (OR 1.56; 95%CI 1.11−2.18). In light of these factors, time in the field could be reduced by having more pediatric emergency physicians and orthopedic surgeons available.

BACKGROUND: In elderly patients with human epidermal growth factor 2-positive breast cancer, adjuvant chemotherapy was associated with decreased quality of life, with relatively small benefits for prognosis. We examined the cost-effectiveness of trastuzumab monotherapy versus adjuvant chemotherapy plus trastuzumab in elderly patients with human epidermal growth factor 2-positive breast cancer. METHODS: A Markov model was developed to evaluate the costs and benefits of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab for elderly patients with human epidermal growth factor 2-positive breast cancer. We built the model with a yearly cycle over a 20-year time horizon and five health states: disease-free, relapse, post-relapse, metastasis and death. The parameters in the model were based on a previous randomized controlled trial and a nationwide administrative database in Japan. The incremental cost-effectiveness ratio, expressed as Japanese yen per the quality-adjusted life-years, was estimated from the perspective of health care payers. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte-Carlo simulations of 10 000 samples were conducted. RESULTS: The incremental cost-effectiveness ratio of trastuzumab monotherapy over adjuvant chemotherapy plus trastuzumab was $\sim$1.8 million Japanese yen /quality-adjusted life-year. The one-way deterministic sensitivity analysis showed that transition probability from disease-free to metastasis status and cost of metastasis status had the greatest influence on the incremental cost-effectiveness ratio. More than half the estimates in the probabilistic sensitivity analysis were located below a threshold of willingness-to-pay of 5 million Japanese yen /quality-adjusted life-year. CONCLUSION: In this first comparative cost-effectiveness analysis of adjuvant chemotherapy plus trastuzumab versus trastuzumab monotherapy in the elderly, the latter was found favorable for elderly patients with human epidermal growth factor 2-positive breast cancer.

BACKGROUND: Patients with traumatic brain injury associated with intracranial hemorrhage are commonly admitted to the intensive care unit (ICU); however, the need for ICU care for patients with isolated traumatic subarachnoid hemorrhage (tSAH) remains unclear. We aimed to investigate the association between the ICU admission practices and outcomes in patients with isolated tSAH. METHODS: This observational study used a nationwide administrative database in Japan. We identified patients with isolated tSAH from the Japanese Diagnostic Procedure Combination inpatient database from July 1, 2010, to March 31, 2020. The primary outcome was in-hospital mortality, whereas the secondary outcomes were neurosurgical interventions, activities of daily living at discharge, and total hospitalization cost. We performed a risk-adjusted mixed-effect regression analysis to evaluate the association between hospital-level ICU admission rates and study outcomes. The ICU admission rates were categorized into quartiles: lowest, middle-low, middle-high, and highest. Moreover, we assessed the robustness of the results with a patient-level instrumental variable analysis. RESULTS: Of the 61,883 patients with isolated tSAH treated at 962 hospitals, 16,898 (27.3%) patients were admitted to the ICU on the day of admission. Overall, 2465 (4.0%) patients died in the hospital, and 783 (1.3%) patients underwent neurosurgical interventions. There was no significant difference between the lowest and highest ICU admission quartile in terms of in-hospital mortality (3.7% vs. 4.3%; adjusted odds ratio 0.93; 95% confidence interval [CI] 0.78-1.10), neurosurgical interventions, and activities of daily living at discharge. However, the total hospitalization cost in the lowest ICU admission quartile was significantly lower than that in the highest quartile (US $3032 vs. $4095; adjusted difference US $560; 95% CI 33-1087). The patient-level instrumental variable analysis did not reveal a significant difference in in-hospital mortality between the patients who were admitted to the ICU and those who were not (risk difference 0.2%; 95% CI - 0.1 to 0.5). CONCLUSIONS: There was no significant association between the ICU admission practices and outcomes in patients with isolated tSAH, whereas higher ICU admission rates were associated with significantly higher hospitalization costs. Our results provide an opportunity for improved health care allocation in the management of patients with isolated tSAH.

BACKGROUND: The appropriate level of postoperative critical care for patients undergoing emergency surgery is unknown. We aimed to assess the outcomes of postoperative patients treated in the intensive care unit (ICU) and high dependency care unit (HDU) after emergency surgery. METHODS: Analysis of national in-patient registry data in Japan from July 2010 to March 2018, including patients undergoing one of 10 emergency surgeries on the day of hospital admission. The exposures were ICU or HDU admission on the day of surgery. The primary outcome was in-hospital mortality. We performed multivariable logistic regression analysis adjusted for patient and hospital characteristics. Results are presented as n (%) and odds ratios (ORs) with 95% confidence intervals. RESULTS: We included 158 149 patients from 646 hospitals. Crude in-hospital mortality for each procedure ranged from 168/8583 (2.0%) for cholecystectomy to 2842/12 958 (21.9%) for patients undergoing surgery for traumatic brain injury. Compared with HDU admission, ICU admission was associated with lower in-hospital mortality among the cohorts for medium-mortality risk procedures (procedure-specific mortality 5-15%) (ICU: 8834/73 616 [12.0%] vs HDU: 2586/25 262 [10.2%]; OR=0.90 [0.85-0.96]; P=0.001), and high-mortality risk procedures (procedures-specific mortality >15%) (ICU: 3445/16 334 [21.1%] vs HDU: 996/4613 [21.6%]; OR=0.86 [0.78-0.96]; P=0.005). There were no differences in mortality for low-mortality risk procedures with procedure-specific mortality <5%. CONCLUSIONS: In this national registry study, postoperative critical care in ICU was associated with lower in-hospital mortality than in HDU for patients undergoing medium-risk and high-risk emergency surgery. Further research is needed to understand the role of critical care for surgical patients.

OBJECTIVES: This study aim to evaluate the effectiveness of fluoroquinolone (FQ) antimicrobial therapy in combination with tetracyclines (TCs) in patients with Japanese spotted fever (JSF) using a nationwide inpatient database in Japan. METHODS: We identified hospitalized patients diagnosed with JSF who were enrolled in the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. Patients who received FQ plus TC on the day of admission were compared with patients who received TC alone on the day of admission, using inverse probability of treatment weighting. The primary outcome was in-hospital mortality. Secondary outcomes were in-hospital complications, total hospitalization costs, and length of hospital stay. RESULTS: We identified 1060 eligible patients. Of these, 434 (41%) received FQ plus TC on the day of admission and 626 (59%) received TC alone on the day of admission. Inverse probability of treatment weighting showed no statistically significant differences between the groups in in-hospital mortality, in-hospital complications, total hospitalization costs, and length of hospital stay. CONCLUSION: This study did not show any significantly improved effectiveness using FQ antimicrobials in combination with TCs for treating JSF. Clinicians may need to be cautious in administering FQ and TC antimicrobials concomitantly in routine practice.

Background: While clinical criteria have been proposed for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) using C-reactive protein (CRP), albumin, and lymphocyte count, there is no substantial basis for their optimal cut-off values. We herein aimed to develop and externally validate clinical criteria for PICS by investigating the optimal cut-off values for these biomarkers using machine-learning approaches and confirmed it with external validation. Methods: To develop criteria, we included ICU patients treated at a tertiary care hospital in Japan between 2018 and 2021 (derivation cohort). We introduced CRP, albumin and lymphocyte counts at around day 14 into six machine-learning models to predict PICS, defined as the compound outcome of the Barthel index (BI) < 70 at hospital discharge and in-hospital death. We incorporated the results of these models to assess the optimal cut-off values for biomarkers. We then developed and externally validated criteria for PICS using a nationwide claims database in Japan (validation cohort). Results: In the derivation cohort, 291 out of 441 patients had BI < 70 or in-hospital death. Based on machine-learning models, the optimal cut-off values for biomarkers to predict them were a CRP of 2.0 mg/dL, albumin of 3.0 g/dL, and a lymphocyte count of 800/μL, with an AUROC of 0.67. In the external validation cohort, 4492 out of 15,302 patients had BI < 70 or in-hospital death. The AUROC of the criteria was 0.71, with sensitivity of 0.71 and specificity of 0.68 to predict PICS. Conclusions: We herein provide a fundamental basis for PICS clinical criteria with CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/μL on day 14. The criteria developed will identify patients with PICS whose long-term mortality and activity of daily living may be poor.

AIM: To evaluate the cost-effectiveness of practices with and without termination-of-resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA), using an analytic model based on a nationwide population-based registry in Japan. METHODS: A combined model using a decision tree and Markov model was developed to compare costs and treatment effectiveness of three scenarios: basic life support (BLS) TOR rules (BLS-rule scenario), advanced life support (ALS) TOR rules (ALS-rule scenario), and no TOR rules (No-rule scenario). A nationwide population-based OHCA registry from January 1 to December 31, 2019 and published data were used. Analyses were performed from healthcare payers' perspectives. Life-time incremental cost-effectiveness ratio (ICER) was determined by the difference in cost between two scenarios, divided by the difference in quality adjusted life year (QALY). RESULTS: The OHCA registry included 126,271 patients (57.3% men; median age, 80 years). The BLS-rule scenario yielded lower cost and less QALY than the ALS-rule scenario and No-rule scenario. With reference to the BLS-rule scenario, the ICERs for the ALS-rule scenario and No-rule scenario were 81,000 and 98,762 USD per QALY, respectively. The BLS-rule scenario was cost-effective in 100% of simulations at the willingness-to-pay threshold in Japan (5 million JPY = 45,455 USD). The willingness-to-pay threshold higher than 80,000 and 204,000 USD were required for the ALS-rule scenario and No-rule scenarios, respectively, to be cost-effective. CONCLUSION: No-rule scenario was not cost-effective compared with BLS-rule scenario within acceptable willingness-to-pay thresholds. Further research on health economics of TOR rules is warranted to support constructive discussion on implementing TOR rules.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used for postpartum hemorrhage (PPH), which is one of the leading causes of maternal mortality worldwide; however, its utility in the obstetrics setting remains unclear. Thus, this study aimed to describe the characteristics, demographics, and mortality of patients with PPH who underwent REBOA. METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database to identify patients with PPH who underwent REBOA from April 2012 to March 2020. We examined the patients' characteristics, interventions administered, and in-hospital mortality. RESULTS: We identified 143 patients with PPH who underwent REBOA. The most common cause of PPH was atonic postpartum hemorrhage (52.4%), followed by disseminated intravascular coagulation (29.4%) and amniotic fluid embolism documented (11.2%). Among patients who delivered at hospitals in which REBOA was performed (n = 55), 38.2% of patients experienced preterm births, and 70.9% delivered via cesarean delivery. The proportion of patients who underwent transcatheter arterial embolization and hysterectomy was 53.8% and 16.1%, respectively. In-hospital mortality was 7.0%. CONCLUSION: The results of the present study could be helpful in clinical decision making and providing patients and families with additional treatment options for PPH. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

OBJECTIVES: Electroconvulsive therapy (ECT) is a widely used treatment for bipolar depression; however, evidence of its effectiveness is not sufficient. This study therefore aimed to evaluate whether early ECT is associated with reduced length of hospital stay. METHODS: In this retrospective cohort study using the Japanese Diagnosis Procedure Combination database, we identified patients admitted for bipolar depression between April 2010 and March 2018. The primary outcome was length of hospital stay, and the secondary outcome was clinical outcomes and total hospitalization costs. Propensity score-matched analyses were performed to compare the outcomes between patients who received ECT within 8 days of admission (early ECT group) and those who did not (control group). RESULTS: We identified 5941 eligible patients, comprising 219 in the early ECT group and 5722 in the control group. After 1:4 propensity score matching, patients in the early ECT group had significantly shorter lengths of hospital stay than those in the control group (53 days in the early ECT group and 73 days in the control group; difference: -20.2 days; 95 % confidence interval: -29.2 to -11.2 days). There was no significant difference in total hospitalization costs between the two groups. In-hospital mortality and fatal complications were rare in both groups. The result was similar in the sensitivity analysis using inverse probability of treatment weighting. LIMITATIONS: Our study was limited by retrospective design and the possibility of unmeasured confounders. CONCLUSIONS: Early ECT was associated with reduced length of hospital stay without increasing total hospitalization costs in patients with bipolar depression.

OBJECTIVE: Exercise immediately after aortic surgery is controversial with limited evidence. The present study aimed to assess whether early rehabilitation commencing within 3 days of aortic surgery improves physical functions at discharge more than usual care in patients after aortic surgery. METHODS: We used the Japanese Diagnosis Procedure Combination database, a nationwide inpatient database from more than 1600 acute care hospitals that covers approximately 75% of all intensive care unit (ICU) beds in Japan. We identified patients who underwent open or endovascular aortic surgery and were admitted to the ICU between July 2010 and March 2018. Patients beginning rehabilitation within 3 days of aortic surgery were defined as the early rehabilitation group and the remaining patients as the usual care group. We used inverse probability of treatment weighting analyses to compare outcomes between the two groups. RESULTS: Among 121,024 eligible patients, there were 44,746 (37.0%) in the early rehabilitation group and 76,278 (63.0%) in the usual care group. In inverse probability of treatment weighting analyses, Barthel index scores at discharge were significantly higher in the early rehabilitation group than in the usual care group (difference, 4.0; 95% confidence interval, 2.8-5.2). The early rehabilitation group had significantly lower in-hospital mortality, lower total hospitalization costs, shorter ICU stay, and shorter hospital stay than the usual care group. CONCLUSION: Early rehabilitation within 3 days of aortic surgery was associated with improved physical functions at discharge, shorter ICU and hospital stays, and lower hospitalization costs without increased mortality.

BACKGROUND: Hormonal therapy and radiotherapy are conducted concurrently or sequentially after breast cancer surgery. It remains unclear whether concurrent or sequential treatment is safer in terms of lung complications. Using a Japanese nationwide database, this study aimed to compare the occurrence of severe lung complications between concurrent and sequential treatments. METHODS: We identified patients who underwent partial mastectomy for stage 0-III breast cancer from July 2010 to March 2020 and received adjuvant hormonal therapy and radiotherapy concurrently (n = 1851) or sequentially (n = 18,429). Two propensity score analyses (1:4 matching and overlap weighting) were conducted to compare hospitalization for radiation pneumonitis and pneumonia within 1 year after surgery, and intensive care unit admission and mortality during the hospitalization. We conducted additional analyses stratified by hormonal drugs (aromatase inhibitors and tamoxifen). RESULTS: The propensity score-matched analysis showed no significant differences in occurrence of hospitalization for radiation pneumonitis (0.27 vs. 0.58%, p = 0.10) and pneumonia (0.16 vs. 0.58%, p = 0.05) between the concurrent and sequential treatments. The overlap propensity score-weighted analysis also showed no significant differences (0.25 vs. 0.56%, p = 0.08 and 0.15 vs. 0.44%, p = 0.06, respectively). Intensive care unit admission and in-hospital mortality did not differ significantly between the two treatments. The stratified analysis showed similar results. CONCLUSION: Our propensity score analyses revealed no significant differences in severe lung complications between concurrent and sequential hormonal therapy with radiotherapy following breast cancer surgery, regardless of the type of hormonal drugs. Clinicians can provide concurrent or sequential treatment with equivalent attention to early lung complications.

OBJECTIVE: This study aimed to investigate urban-rural inequalities in care and outcomes of severe traumatic brain injury (TBI). METHODS: This observational study identified patients with severe TBI from the Japanese Diagnosis Procedure Combination inpatient database from 1 July 2010 to 31 March 2020. The patients were dichotomized into rural and urban groups based on the geographical location of their residence, using the urban employment area scheme. The primary outcome measure was in-hospital mortality. Multivariable regression analyses adjusted for patient-level covariates were performed to compare the outcomes between the 2 groups. RESULTS: A total of 48,910 patients (rural group, n = 5423; urban group, n = 43,487) were evaluated. In-hospital mortality was significantly higher in the rural group than that in the urban group (49.9% vs. 45.1%; adjusted odds ratio [OR], 1.26; 95% confidence interval [CI], 1.18-1.35). The standardized in-hospital mortality of the rural group was consistently higher than that of the urban group in each fiscal year, and there was no significant trend for closing the gap (P for trend = 0.95). Patients in the rural group were less likely to undergo craniotomy/craniectomy (adjusted OR, 0.83; 95% CI, 0.77-0.89) and intracranial pressure monitoring (adjusted OR, 0.53; 95% CI, 0.46-0.61) and achieve independent activities of daily living at discharge (8.2% vs. 10.5%, adjusted OR, 0.85; 95% CI, 0.76-0.96). CONCLUSIONS: There are significant urban-rural inequalities in TBI in Japan, and the gap in in-hospital mortality has not improved over the last 10 years. Improving TBI care in rural communities may be a target for reducing disparities in health care.

AIMS: Several studies have reported a high predictive ability of the Sequential Organ Failure Assessment (SOFA) score for in-hospital mortality specifically for patients with cardiac critical illnesses, however, differences according to the admission classification (surgical or non-surgical) are unknown. The present study aimed to evaluate the predictive ability of the SOFA score in surgical and non-surgical patients with cardiac critical illnesses. METHODS AND RESULTS: Using the Japanese nationwide Diagnosis Procedure Combination database, we identified patients with cardiac critical illnesses, defined as patients admitted to the intensive care unit (ICU) and treated by cardiologists or cardiovascular surgeons as their physicians in charge from April 2018 to March 2020. The discriminatory ability of the SOFA score for in-hospital mortality was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Among 52 819 eligible patients with available data on their SOFA scores, 33 526 (64%) were postoperative cardiac surgeries. The median SOFA score on ICU admission was 5.0 (interquartile range, 2.0-8.0) and overall in-hospital mortality 6.8%. The AUROC of the SOFA score was 0.75 [95% confidence interval (CI), 0.75-0.76]. In the subgroup analyses, the AUROCs were 0.76 (95% CI, 0.74-0.77) in the surgical patients, 0.83 (95% CI, 0.83-0.84) in the non-surgical patients, and 0.88 (95% CI, 0.87-0.89) in the non-surgical acute coronary syndrome patients. CONCLUSIONS: The predictive ability of the SOFA score on the day of ICU admission for in-hospital mortality was confirmed to be acceptable in the patients with cardiac critical illnesses and varied according to the admission classification and primary diagnoses.

Rationale: In Japan, the government officially issued intensive care unit (ICU) admission criteria that require ICUs to admit patients who need a certain level of monitoring and procedures to ensure their reimbursement for ICU costs from April 2014. Objectives: To assess whether the newly issued health policy on ICU admission criteria based on financial incentives for monitoring and procedures had any impact on clinical practices, outcomes, and ICU bed occupancy. Methods: Using a nationwide inpatient health claims database in Japan, we identified patients who were admitted to the ICU from April 2012 to March 2018. Outcomes were monitoring and procedures in the ICU, clinical outcomes, and ICU bed occupancy. The outcomes of monitoring and procedures and clinical outcomes were adjusted for patient characteristics. Interrupted time-series analyses were used to compare the trends in outcomes for two separate periods before and after the issue of the new health policy on ICU admission criteria in April 2014. Results: A total of 1,660,601 patients in 259 ICU-equipped hospitals were eligible. There were significant upward slope changes between the pre- and post-issue periods for all monitoring and procedures in the ICU, including invasive arterial pressure monitoring (5.62% change in trend per year; 95% confidence interval [CI], 4.75-6.49%) and central venous pressure monitoring (1.22% change in trend per year; 95% CI, 0.78-1.67%). There was no significant slope change between the pre- and post-issue periods for in-hospital mortality, but there were significant upward slope changes for complications of pneumonia (0.27% change in trend per year; 95% CI, 0.14-0.39%) and catheter-related bloodstream infection (0.02% change in trend per year; 95% CI, 0.00-0.14%). There were also significant upward slope changes in length of hospital stay, length of ICU stay, and hospitalization costs between the pre- and post-issue periods. There was no significant slope change between the pre- and post-issue periods for ICU bed occupancy. Conclusions: The health policy on ICU admission criteria based on financial incentives for actions taken by providers was associated with increased monitoring and procedures, complications, lengths of hospital and ICU stay, and hospitalization costs without decreasing ICU bed occupancy.

OBJECTIVES: To compare the outcomes of patients with acute myocardial infarction who were treated in ICUs versus high-dependency care units (HDUs). DESIGN: A nationwide, propensity score-matched, retrospective cohort study of a national administrative inpatient database in Japan from July 2010 to March 2018. SETTING: Six hundred sixty-six acute-care hospitals with ICU and/or HDU beds covering about 75% of all ICU beds and 70% of all HDU beds in Japan. PATIENTS: Adult patients who were hospitalized for acute myocardial infarction and admitted to the ICU or HDU on the day of hospital admission. Propensity score-matching analysis was performed to compare the inhospital mortality between patients treated in the ICU and HDU on the day of hospital admission. INTERVENTIONS: ICU or HDU admission on the day of hospital admission. MEASUREMENTS AND MAIN RESULTS: Of 135,142 eligible patients, 89,382 (66%) were admitted to the ICU and 45,760 (34%) were admitted to the HDU on the day of admission. After propensity score matching, there was no statistically significant difference in inhospital mortality between the ICU and HDU groups (5.0% vs 5.5%; difference, -0.5%; 95% CI, -1.0% to 0.1%). In the subgroup analyses, inhospital mortality was significantly lower in the ICU group than that in the HDU group among patients with Killip class IV (25.6% vs 28.4%; difference, -2.9%; 95% CI, -5.4% to -0.3%), patients who underwent intubation (40.0% vs 46.6%; difference, -6.6%; 95% CI, -10.6% to -2.7%), and patients who received mechanical circulatory support (21.8% vs 24.7%; difference, -2.8%; 95% CI, -5.5% to -0.2%). CONCLUSIONS: Critical care in the ICU compared with that in the HDU was not associated with reduced inhospital mortality among the entire cohort of patients with acute myocardial infarction but was associated with reduced inhospital mortality among the subsets of patients with Killip class IV, intubation, or mechanical circulatory support.

PURPOSE: The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease-2019 (COVID-19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID-19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre-admission anticoagulation treatment and three outcomes: in-hospital death, VTE, and major bleeding among hospitalized COVID-19 patients in Japan. METHODS: Using a large-scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID-19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre-admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in-hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre-admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes. RESULTS: Among the 2612 analytic patients, 179 (6.9%) had pre-admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in-hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre-admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75-2.08) for in-hospital death, 0.21 (0.02-1.97) for VTE, and 2.63 (0.80-8.65) for major bleeding. Several sensitivity analyses did not change the results. CONCLUSIONS: We found no evidence that pre-admission anticoagulation treatment was associated with in-hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding.

PURPOSE: Antiplatelet agents may attenuate inflammatory and coagulation responses in patients with sepsis. This study aimed to examine the association between pre-sepsis antiplatelet therapy and survival outcomes in patients with sepsis. MATERIALS AND METHODS: This was a secondary analysis of a Japanese multicenter registry dataset. Participants aged >16 years who were admitted to intensive care units for the treatment of severe sepsis (Sepsis 2 criteria) were dichotomized, according to their pretreatment status with antiplatelet agents. The primary outcome was in-hospital mortality. The data were analyzed using inverse probability of treatment weighting (IPTW) with a propensity score for pre-existing treatment using antiplatelet medication after multiple imputation. RESULTS: Data from a total of 1184 eligible patients (2016-2017) were analyzed. A total of 175 patients were pretreated with antiplatelet medication. After IPTW, the patients' characteristics were well balanced between the groups. The in-hospital mortality rate among patients pretreated with antiplatelet medication was significantly lower than that among patients pretreated without antiplatelet medication (18.15% vs. 25.31%, difference: -7.86%, 95% confidence interval [CI]: -14.3 to -1.4, p = 0.016). CONCLUSIONS: In this study, pretreatment with antiplatelet medication before the onset of sepsis was associated with decreased in-hospital mortality rates.

PURPOSE: We aimed to develop and validate models for predicting new-onset functional impairment after intensive care unit (ICU) admission with predictors routinely collected within 2 days of admission. METHODS: In this multi-center retrospective cohort study of acute care hospitals in Japan, we identified adult patients who were admitted to the ICU with independent activities of daily living before hospitalization and survived for at least 2 days from April 2014 to October 2020. The primary outcome was functional impairment defined as Barthel Index ≤ 60 at hospital discharge. In the internal validation dataset (April 2014 to March 2019), using routinely collected 94 candidate predictors within 2 days of ICU admission, we trained and tuned the six conventional and machine-learning models with repeated random sub-sampling cross-validation. We computed the variable importance of each predictor to the models. In the temporal validation dataset (April 2019 to October 2020), we measured the performance of these models. RESULTS: We identified 19,846 eligible patients. Functional impairment at discharge was developed in 33% of patients (n = 6488/19,846). In the temporal validation dataset, all six models showed good discrimination ability with areas under the curve above 0.86, and the differences among the six models were negligible. Variable importance revealed newly detected early predictors, including worsened neurologic conditions and catabolism biomarkers such as decreased serum albumin and increased blood urea nitrogen. CONCLUSION: We successfully developed early prediction models of new-onset functional impairment after ICU admission that achieved high performance using only data routinely collected within 2 days of ICU admission.

OBJECTIVES: To evaluate the contribution of a preextubation chest X-ray (CXR) to identify the risk of extubation failure in mechanically ventilated patients. DESIGN: Retrospective cohort study. SETTINGS: ICUs in a tertiary center (the Medical Information Mart for Intensive Care IV database). PATIENTS: Patients greater than or equal to 18 years old who were mechanically ventilated and extubated after a spontaneous breathing trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,066 mechanically ventilated patients, 132 patients (12%) experienced extubation failure, defined as reintubation or death within 48 hours of extubation. To predict extubation failure, we developed the following models based on deep learning (EfficientNet) and machine learning (LightGBM) with the training data: 1) model using only the rapid-shallow breathing index (RSBI), 2) model using RSBI and CXR, 3) model using all candidate clinical predictors (i.e., patient demographics, vital signs, laboratory values, and ventilator settings) other than CXR, and 4) model using all candidate clinical predictors with CXR. We compared the predictive abilities between models with the test data to investigate the predictive contribution of CXR. The predictive ability of the model using CXR as well as RSBI was not significantly higher than that of the model using only RSBI (c-statistics, 0.56 vs 0.56; p = 0.95). The predictive ability of the model using clinical predictors with CXR was not significantly higher than that of the model using all clinical predictors other than CXR (c-statistics, 0.71 vs 0.70; p = 0.12). Based on SHapley Additive exPlanations values to interpret the model using all clinical predictors with CXR, CXR was less likely to contribute to the predictive ability than other predictors (e.g., duration of mechanical ventilation, inability to follow commands, and heart rate). CONCLUSIONS: Adding CXR to a set of other clinical predictors in our prediction model did not significantly improve the predictive ability of extubation failure in mechanically ventilated patients.

BACKGROUND: Whether the routine use of the ICU after major elective surgery improves postoperative outcomes is not well established. OBJECTIVES: To describe the association between use of postoperative ICU admission and clinical outcomes for patients undergoing major elective surgery. DESIGN: Observational study. SETTING: Nationwide inpatient database in Japan, July 2010 to March 2018. PATIENTS: Patients undergoing one of 15 major elective orthopaedic, gastrointestinal, neurological, thoracic or cardiovascular surgical procedures. INTERVENTION: ICU admission on the day of surgery. ICU was defined as a separate unit providing critical care services with around-the-clock physician staffing and nursing, the equipment necessary for critical care and a nurse-to-patient ratio at least one to two. MAIN OUTCOME: In-hospital mortality. Patient-level and hospital-level analyses were performed. RESULTS: Overall, 2 011 265 patients from 1524 hospitals were assessed. The cohort size ranged from 38 547 patients in 467 hospitals for surgical clipping for cerebral aneurysms to 308 952 patients in 599 hospitals for spinal fixation, laminectomy or laminoplasty. In the patient-level analyses, there were no significant mortality differences among patients undergoing the 12 major noncardiovascular surgical procedures, whereas postoperative ICU admission was associated with trends towards lower in-hospital mortality among patients undergoing coronary artery bypass grafting, risk difference -1.0% (95% CI -1.8 to -0.1) open aortic aneurysm repair, risk difference -0.6% (95% CI -1.3 to 0.1), and heart valve replacement, risk difference -0.7% (95% CI - 1.6 to 0.1). In the hospital-level analyses, similar to the results of the patient-level analyses, a higher proportion of postoperative ICU admission at hospital level was associated with trends toward lower in-hospital mortality for patients undergoing the three cardiovascular surgical procedures. CONCLUSION: This nationwide observational study showed that postoperative ICU admission was associated with improved survival outcomes among patients undergoing three types of cardiac surgery but not among patients undergoing low-risk elective surgery.

BACKGROUND: Although numerous studies have investigated out-of-hospital cardiac arrest, few studies have been conducted on in-hospital cardiac arrest (IHCA). Knowledge of the nationwide epidemiology of IHCA in Japan, with its super-aging society, is important to understand the current situation of IHCA and to establish evidenced-based medicine in the future. The present study aimed to determine the incidence and outcomes of IHCA and their trends in Japan. METHODS: This observational cohort study was performed using a national administrative inpatient database for more than 1600 acute-care hospitals covering about 50% of all acute-care hospital beds in Japan from April 2011 to March 2018. We defined cardiac arrest patients who received cardiopulmonary resuscitation (chest compression) during hospitalization as IHCA. We excluded out-of-hospital cardiac arrest patients from the source population. The incidence of IHCA per 1000 hospital admissions and survival to discharge rate was reported with trend analyses by calendar year 2011-2017. RESULTS: Among 53,871,101 hospitalized patients without out-of-hospital cardiac arrest patients in 1626 hospitals, 2,136,038 (4.0%) had cardiac arrest. Of them, 274,664 (12.9%) received cardiopulmonary resuscitation at least once during hospitalization and were identified as IHCA, and 1,861,374 (87.1%) did not receive cardiopulmonary resuscitation. The incidence of IHCA per 1000 hospital admissions was 5.1, with a significant decreasing trend from 6.1 in 2011 to 4.6 in 2017 (P for trend = 0.033). Our estimated incidence can be translated to approximately 87,000 IHCA cases in Japan each year. The percentage of IHCA patients among cardiac arrest patients was 12.9%, with a significant decreasing trend from 14.0% in 2011 to 12.2% in 2017 (P for trend = 0.006). The overall rate of survival to discharge was 12.7%, with a significant increasing trend from 10.5% in 2011 to 14.0% in 2017 (P for trend < 0.001). CONCLUSIONS: We found substantial associations between mortality and loss of health and IHCA in Japan. The incidence of IHCA showed a decreasing trend over time, the percentage of treated cardiac arrest patients also had a decreasing trend, and the overall survival to discharge rate improved over time.

OBJECTIVE: The aim of this study was to determine the prognosis, clinical course, and current management of severe interstitial lung disease (ILD) associated with myositis in Japan. METHODS: We conducted a retrospective descriptive study using a nationwide database for inpatient care of acute illness in Japan. Among a total of ~66 million inpatient admissions, we identified patients with severe ILD associated with polymyositis (PM) or dermatomyositis (DM) who required mechanical ventilation and methylprednisolone pulse therapy (≥1 gm/day of methylprednisolone) from July 2010 to March 2018. RESULTS: We identified 155 patients with PM and 394 with DM who fulfilled the above criteria. The median age of patients was 65 years; DM patients were significantly younger than PM patients (64 versus 68 years; P < 0.001). The numbers of patients who were treated with calcineurin inhibitors, intravenous cyclophosphamide, and polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) were 403 (73.4%), 318 (57.9%), and 78 (14.2%), respectively. All these treatments were given significantly more frequently to the patients with DM compared with those with PM. The uses of other treatment options were much less frequent. The median periods after hospitalization when methylprednisolone pulse therapy, calcineurin inhibitors, mechanical ventilation, intravenous cyclophosphamide, and PMX-DHP were initiated and in-hospital death occurred among patients with DM were 2, 4, 7, 8, 17, and 36 days, respectively. In-hospital mortality was significantly higher in patients with DM than in those with PM (76.6% versus 56.8%; P < 0.001). CONCLUSION: The mortality of patients with myositis-associated severe ILD who require mechanical ventilation is extremely high despite aggressive and prompt interventions.

BACKGROUND: COVID-19 has worse mortality than influenza in American and European studies, but evidence from the Western Pacific region is scarce. METHODS: Using a large-scale multicenter inpatient claims data in Japan, we identified individuals hospitalised with COVID-19 in 2020 or influenza in 2017-2020. We compared patient characteristics, supportive care, and in-hospital mortality, with multivariable logistic regression analyses for in-hospital mortality overall, by age group, and among patients with mechanical ventilation. FINDINGS: We identified 16,790 COVID-19 patients and 27,870 influenza patients, with the different age distribution (peak at 70-89 years in COVID-19 vs. bimodal peaks at 0-9 and 80-89 years in influenza). On admission, the use of mechanical ventilation was similar in both groups (1·4% vs. 1·4%) but higher in the COVID-19 group (3·3% vs. 2·5%; p<0·0001) during the entire hospitalisation. The crude in-hospital mortality was 5·1% (856/16,790) for COVID-19 and 2·8% (791/27,870) for influenza. Adjusted for potential confounders, the in-hospital mortality was higher for COVID-19 than for influenza (adjusted odds ratio [aOR] 1·83, 95% confidence interval [CI] 1·64-2·04). In age-stratified analyses, the aOR (95%CI) were 0·78 (0·56-1·08) and 2·05 (1·83-2·30) in patients aged 20-69 years and ≥70 years, respectively (p-for-interaction<0·0001). Among patients with mechanical ventilation, the aOR was 0·79 (0·59-1·05). INTERPRETATION: Patients hospitalised with COVID-19 in Japan were more likely to die than those with influenza. However, this was mainly driven by findings in older people, and there was no difference once mechanical ventilation was started. FUNDING: Ministry of Health, Labour and Welfare of Japan (21AA2007).

BACKGROUND: The association of simultaneous bilateral total hip arthroplasty (THA) with postoperative deep venous thrombosis (DVT) remains controversial. The aim of the study is to determine whether simultaneous bilateral THA without chemoprophylaxis has a higher risk than unilateral THA without chemoprophylaxis. METHODS: This is a population-based retrospective cohort study of all adults who underwent primary THA without any anticoagulant or antiplatelet therapy between July 2012 and March 2021 at the Department of Orthopedic Surgery, Toranomon Hospital, Tokyo, Japan. The association of simultaneous bilateral THA with postoperative DVT was examined by unadjusted analysis and overlap propensity score weighting. The primary outcome was the incidence of DVT (confirmed by ultrasonography of the lower limb veins) within 7 days postoperatively. RESULTS: Of the 557 consecutive patients who underwent primary THA in the study period, 458 met the inclusion criteria. The mean (standard deviation) age of these patients was 67 (11.7) years, and 364 (79.5%) were women; 75 (16.4%) of the 458 patients underwent simultaneous bilateral THA, and 383 (83.6%), unilateral THA. A total of 64 patients (14.0%) developed a postoperative venous thromboembolism, all of which were a distal DVT. The overlap weighting analysis found no significant difference in the incidence of postoperative DVT complications among patients who underwent simultaneous bilateral THA and those who underwent unilateral THA (31.1 [13.6%] vs 22.9 [10.0%], respectively; risk ratio, 1.36; 95% confidence interval, 0.67 to 2.77; P = .40). CONCLUSIONS: Our findings indicate that the occurrence of DVT within 7 days after surgery is not significantly different between patients undergoing simultaneous bilateral THA or unilateral THA without any anticoagulant or antiplatelet therapy. LEVEL OF EVIDENCE: Level II-III.

AIMS: Little is known about the difference in outcomes between young and old patients who received extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate the differences in outcomes between those aged ≥75 years and <75 years who experienced OHCA and were resuscitated with ECPR. METHODS AND RESULTS: We performed a secondary analysis of a nationwide prospective cohort study using the Japanese Association for Acute Medicine OHCA registry. We identified patients aged ≥18 years with OHCA who received ECPR. The patients were classified into three age groups (18-59 years, 60-74 years, and ≥75 years). The primary outcome was a 1-month neurological outcome. To examine the association between age and 1-month neurological outcome, we performed logistic regression analyses fitted with generalized estimating equations. From 2014 to 2017, we identified 875 OHCA patients aged ≥18 years who received ECPR. The proportion of patients who survived with favourable neurological outcome in the patients aged 18-59 years, 60-74 years, and ≥75 years were 15% (64/434), 8.9% (29/326), and 1.7% (2/115), respectively. In the multivariable analysis, compared with the age of 18-59 years, the proportions of favourable neurological outcomes were significantly lower in patients aged 60-74 years [adjusted odds ratio (OR), 0.44; 95% confidence interval (CI), 0.32-0.61] and those aged ≥75 years (adjusted OR, 0.26; 95% CI, 0.11-0.59). CONCLUSION: Advanced age (age ≥75 years in particular) was significantly associated with poor neurological outcomes in patients with OHCA who received ECPR.

BACKGROUND: The effectiveness of glucocorticoids in preventing biphasic reactions in patients with anaphylaxis remains controversial. OBJECTIVE: We evaluated the effects of glucocorticoids on rates of biphasic reactions in hospitalized patients with anaphylaxis treated with adrenaline. METHODS: In this retrospective observational study using a national inpatient database in Japan, we identified 31,570 hospitalized patients with anaphylaxis treated with adrenaline on the day of admission. We divided them into two groups: those who were treated with adrenaline plus glucocorticoids and those who received adrenaline only on the day of admission. The primary outcome was the occurrence of a biphasic reaction, defined as requiring two or more ampules of adrenaline within 7 days of admission. We performed a one-to-four propensity score matching analysis to compare the outcomes between the two groups. RESULTS: Of the 31,570 eligible patients, 28,145 (89.2%) were treated with glucocorticoids on the day of admission. The overall percentage of biphasic reactions within 7 days of admission was 11.2%. One-to-four propensity score matching created matched cohorts of 3,425 patients in the control group and 13,700 patients in the glucocorticoid group. After propensity score matching, there were no significant differences in rates of biphasic reactions (10.7% in the glucocorticoids group vs. 10.5% in the control group; odds ratio, 1.03; 95% confidence interval, 0.85-1.24; p = 0.77) between patients with anaphylaxis treated with and without glucocorticoids on the day of admission. CONCLUSION: Our findings do not support the use of glucocorticoids to prevent biphasic reactions in hospitalized patients with severe anaphylaxis requiring adrenaline.

BACKGROUND: A structure and staffing model similar to that in general intensive care unit (ICUs) is applied to cardiac intensive care unit (CICUs) for patients with acute heart failure. However, there is limited evidence on the structure and staffing model of CICUs. The present study aimed to assess whether critical care for patients with acute heart failure in the ICUs is associated with improved outcomes than care in the high-dependency care units (HDUs), the hospital units in which patient care levels and costs are between the levels found in the ICU and general ward. METHODS: This nationwide, propensity score-matched, retrospective cohort study was performed using a national administrative inpatient database in Japan. We identified all patients who were hospitalized for acute heart failure and admitted to the ICU or HDU on the day of hospital admission from April 2014 to March 2019. Propensity score-matching analysis was performed to compare the in-hospital mortality between acute heart failure patients treated in the ICU and HDU on the day of hospital admission. RESULTS: Of 202,866 eligible patients, 78,646 (39%) and 124,220 (61%) were admitted to the ICU and HDU, respectively, on the day of admission. After propensity score matching, there was no statistically significant difference in in-hospital mortality between patients who were admitted to the ICU and HDU on the day of admission (10.7% vs. 11.4%; difference, - 0.6%; 95% confidence interval, - 1.5% to 0.2%). In the subgroup analyses, there was a statistically significant difference in in-hospital mortality between the ICU and HDU groups among patients receiving noninvasive ventilation (9.4% vs. 10.5%; difference, - 1.0%; 95% confidence interval, - 1.9% to - 0.1%) and patients receiving intubation (32.5% vs. 40.6%; difference, - 8.0%; 95% confidence interval, - 14.5% to - 1.5%). There were no statistically significant differences in other subgroup analyses. CONCLUSIONS: Critical care in ICUs was not associated with lower in-hospital mortality than critical care in HDUs among patients with acute heart failure. However, critical care in ICUs was associated with lower in-hospital mortality than critical care in HDUs among patients receiving noninvasive ventilation and intubation.

Previous literature has provided conflicting results regarding the associations between early surgery and postoperative outcomes in elderly patients with distal femur fractures. Using data from the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2019, we identified elderly patients who underwent surgery for distal femur fracture within two days of hospital admission (early surgery group) or at three or more days after hospital admission (delayed surgery group). Of 9678 eligible patients, 1384 (14.3%) were assigned to the early surgery group. One-to-one propensity score matched analyses showed no significant difference in 30-day mortality between the early and delayed groups (0.5% versus 0.5%; risk difference, 0.0%; 95% confidence interval, -0.7% to 0.7%). Patients in the early surgery group had significantly lower proportions of the composite outcome (death or postoperative complications), shorter hospital stays, and lower total hospitalization costs than patients in the delayed surgery group. Our results showed that early surgery within two days of hospital admission for geriatric distal femur fracture was not associated with a reduction in 30-day mortality but was associated with reductions in postoperative complications and total hospitalization costs.

OBJECTIVE: Current data suggest that a history of traumatic open skin wounds may be a risk factor for infectious endocarditis, with limited evidence. We tested the hypothesis that traumatic skin wound is a risk factor for infectious endocarditis. METHODS: Using the Japan Medical Data Center (JMDC) database (4 650 927 people aged 20-64 years, 2012-2018) and the Kumamoto database (493 414 people aged ≥65 years, 2012-2017), we conducted nested case-control and self-controlled case series (SCCS) analyses. RESULTS: In the JMDC database, 544 cases hospitalised for infective endocarditis (IE) were matched with 2091 controls; 2.8% of cases and 0.5% of controls were exposed to traumatic skin wounds in the previous 1-4 weeks, with an adjusted OR of 4.31 (95% CI 1.74 to 10.7). In the Kumamoto database, 4.0% (27/670) of cases and 1.1% (29/2581) of controls were exposed to traumatic skin wounds in the previous 1-4 weeks, with an adjusted OR of 4.15 (95% CI 2.04 to 8.46). In the SCCS, the incidence rate ratios for IE were 2.61 (95% CI 1.67 to 4.09), 1.73 (95% CI 1.01 to 2.94), 1.19 (95% CI 0.63 to 2.27) and 1.52 (95% CI 0.82 to 2.74) for the Kumamoto database and 3.78 (95% CI 2.07 to 6.92), 1.58 (95% CI 0.64 to 3.89), 1.60 (95% CI 0.65 to 3.94) and 1.29 (95% CI 0.47 to 3.53) for the JMDC database at 1-4, 5-8, 9-12 and 13-16 weeks after traumatic skin wound, respectively, compared with the baseline period. CONCLUSIONS: This study suggests that traumatic skin wound is a risk factor for IE 1-4 weeks after the wound.

BACKGROUND: Daikenchuto, a Japanese herbal Kampo medicine, is used to improve gastrointestinal motility in critically ill patients with enteral feeding intolerance (EFI) in Japan. The present study aimed to investigate the effect of Daikenchuto for critically ill patients with EFI. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified mechanically ventilated patients in intensive care units (ICUs) who had EFI during mechanical ventilation. We defined EFI as receipt of intravenous metoclopramide during mechanical ventilation. Patients who started Daikenchuto within 2 days of EFI onset were defined as the Daikenchuto group, and the remaining patients were defined as the control group. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. RESULTS: A total of 61,454 patients were included. Of these, 8842 patients (14%) were in the Daikenchuto group. One-to-one propensity score matching created 8701 matched pairs. After propensity score matching, the total number of days receiving enteral nutrition within 28 days of EFI onset was significantly longer in the Daikenchuto group than in the control group (risk difference, 0.9 days; 95% CI, 0.5-1.3 days). There were no significant differences in 28-day in-hospital mortality, hospital-acquired pneumonia, ventilator-free days, length of ICU stay, time to discharge alive, and adverse complications. CONCLUSION: This nationwide observational study suggested that use of Daikenchuto may increase the total number of days receiving enteral nutrition in mechanically ventilated patients with EFI.

Rationale: Extracorporeal membrane oxygenation (ECMO) treatment is widely used worldwide, and many hospitals consider using antibiotics to prevent nosocomial infection in patients receiving ECMO treatment. However, the efficacy of antimicrobial prophylaxis for patients receiving ECMO treatment remains unclear. Objectives: To evaluate the efficacy of prophylactic antibiotics for patients receiving ECMO treatment. Methods: This retrospective cohort study was performed using data recorded in the Japanese Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2017. We compared in-hospital mortality, nosocomial pneumonia, acute kidney injury, and diarrhea between patients receiving prophylactic antibiotics (prophylaxis group) and those not receiving antibiotics (control group) using propensity score matching. For in-hospital mortality and nosocomial pneumonia, multivariable logistic regression models fitted using a generalized estimating equation, stabilized inverse probability of treatment weighting, and instrumental variable analysis were performed. Results: We identified 9,615 eligible patients and classified them into the prophylaxis (n = 5,552) and control (n = 4,063) groups. In the propensity score-matched analysis, 3,650 pairs were generated. Significant differences between the prophylaxis group and the control group were detected in the in-hospital mortality (56.4% vs. 59.8%; risk difference, -3.7%; 95% confidence interval [CI], -6.0 to -1.3) and nosocomial pneumonia (12.9% vs. 15.3%; risk difference, -2.4%; 95% CI: -4.3 to -0.6). In the multivariable logistic regression models fitted using a generalized estimating equation, stabilized inverse probability of treatment weighting, and instrumental variable analysis, the point estimates suggested a direction similar to that found in the propensity score analysis. The proportions of patients with acute kidney injury or diarrhea did not significantly increase with the use of prophylactic antibiotics. Conclusions: Using prophylactic antibiotics during ECMO treatment was associated with reduced in-hospital mortality and lower proportions of patients with nosocomial pneumonia. Future prospective studies are needed to validate these results.

BACKGROUND: The effects and safety of early rehabilitation in intensive care units (ICU) remain unclear for patients after acute myocardial infarction (AMI). METHODS: Using Japanese Diagnosis Procedure Combination inpatient data between July 2010 and March 2018, we identified 31,603 adult patients with AMI who underwent percutaneous coronary intervention on the day of admission and who were admitted to the ICU for more than three consecutive days. Patients who started a rehabilitation program within three days of ICU admission were included in the early rehabilitation group, while others were included in the usual care group. The primary outcome was activities of daily living (ADL) at discharge, as measured using the Barthel Index score. We conducted inverse probability of treatment weighting analyses. RESULTS: The data of 31,603 patients were examined, 5,147 of whom were assigned to the early rehabilitation group. In the weighted cohort, the Barthel Index score at discharge was not significantly different between the two groups. The early rehabilitation group had a significantly shorter hospital stay, shorter ICU stay, and lower total hospitalization costs. CONCLUSIONS: No correlations were observed between early rehabilitation and ADL at discharge. However, the present results suggest that early rehabilitation is safe and associated with lower hospital costs and shorter hospital stays after AMI.

BACKGROUND: Previous prospective studies have suggested that spouses of patients who are admitted to the intensive care unit (ICU) have a high prevalence of mental disorders, termed post-intensive care syndrome-family (PICS-F). However, it remains unclear whether the patient's ICU admission is associated with the occurrence of mental disorders in the spouse outside of the prospective study setting. We therefore investigated the proportion of ICU patients' spouses who visited medical facilities for mental disorders and the association between ICU admission of a patient and mental disorders in the spouse using real-world data. METHODS: This was a retrospective matched-pair cohort study using commercially available, routinely collected administrative claims data. As the study population, we identified all married couples (both wife and husband) who were registered in the database from 1 April 2012 to 31 August 2018 using family identification codes. We identified spouses of patients who were admitted to the ICU for more than 2 days as the exposure group and defined the date of admission to the ICU as the index date. We randomly matched four individuals in the non-exposure group with one individual in the exposure group. The primary outcome was any PICS-F-related mental disorder in the spouses within 6 months from the index date. As a sensitivity analysis, we also investigated the proportion and association of individuals (excluding spouses) with a history of mental disorders. RESULTS: Among 1,082,208 married couples, we identified 8490 spouses of ICU patients, and they were matched with 33,946 individuals. The proportion of any PICS-F-related mental disorder within 6 months from the index date was 12.8% in ICU patients' spouses and 11.3% in the matched individuals (adjusted odds ratio, 1.29; 95% confidence interval, 1.03-1.42). The sensitivity analysis showed significant associations between ICU admission and spouses' mental disorders. CONCLUSIONS: Spouses of patients who were admitted to the ICU had a slightly higher risk of mental disorders within 6 months than spouses of patients who were not admitted to the ICU.

INTRODUCTION: In this present study, we aimed to assess whether care in resource-rich intensive care unit (ICU) was associated with lower ICU mortality compared with care in standard ICU. METHODS: This retrospective cohort study used administrative data that are routinely collected in Japan. Using the Japanese Diagnosis Procedure Combination inpatient database, we identified patients aged >15 years who were admitted to the ICU from April 2016 to March 2019. We defined resource-rich ICUs as ICUs with two or more intensivists as full-time employees, ≥20 m2 per ICU bed, and a medical engineer in the hospital 24 hours per day; other ICUs were categorized as standard ICUs. The primary outcome was ICU mortality. A generalized estimating equation approach with ICUs as the clusters was used to compare ICU mortality between the two groups. RESULTS: Of the 789,630 eligible patients from 458 ICUs, 237,138 (30%) were treated in the 111 resource-rich ICUs, whereas 552,492 (70%) were treated in the 347 standard ICUs. The crude ICU mortality rate was 3.6% (8443/237,138) among patients admitted to resource-rich ICUs, while it was 4.3% (23,490/552,492) among those admitted to standard ICUs. The results of the generalized estimating equation analysis showed that patients treated in resource-rich ICUs tended to have lower ICU mortality compared to patients treated in standard ICUs (difference, -0.4%; 95% confidence interval, -0.8%-0.0%). CONCLUSIONS: The findings of this nationwide study suggest that, compared with care in standard ICUs, care in resource-rich ICUs is associated with lower ICU mortality. This study showed the overall effect of treatment in hospitals with resource-rich ICUs including intensivist staffing and greater hospital resources. Further studies are required to assess the effects of organizational factors on mortality.

OBJECTIVES: We aimed to investigate the effect of intravenous cyclophosphamide (CYC) as the initial therapy in patients with acute exacerbation of rheumatoid arthritis-related interstitial lung disease. METHODS: This was a retrospective observational study. Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified patients with acute exacerbation of rheumatoid arthritis-related interstitial lung disease (RA-ILD) who received high-dose methylprednisolone within 3 days after admission. RA-ILD was defined as having either the diagnosis of RA-ILD or the diagnoses of both RA and ILD, based on the ICD-10 codes recorded by attending physicians. Patients were divided into two groups: those receiving intravenous CYC within 3 days after admission (CYC group) and those who did not (control group). One-to-four propensity-score matching analyses were performed. RESULTS: A total of 6130 eligible patients were included. After propensity score matching, 129 patients in the CYC group and 516 patients in the control group were further analyzed. 90-day in-hospital mortality, defined as all-cause mortality during hospitalization within 90 days after admission, was not significantly different between the CYC and control groups (50.4% versus 42.2%, hazard ratio 1.20, 95% confidence interval 0.91-1.58). A larger proportion of patients in the CYC group received platelet transfusion than that in the control group (7.0% versus 2.3%, odds ratio 3.05, 95% confidence interval 1.20-7.73). CONCLUSION: In this retrospective database study, the initial therapy with CYC did not show a survival benefit in patients with acute exacerbation of RA-ILD. CYC was associated with a larger proportion of platelet transfusion.

OBJECTIVES: This study aimed to evaluate whether early electroconvulsive therapy (ECT) can reduce length of hospital stay and total hospitalization costs in major depressive disorder (MDD) patients. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from April 2011 to March 2018 linked with the Annual Report for Functions of Medical Institutions, we identified patients admitted for MDD. Patients who received ECT within 8 days of admission were assigned to the early ECT group and the remaining patients to the control group. The primary outcomes were length of hospital stay and total hospitalization costs. The secondary outcomes were in-hospital mortality and fatal adverse events. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. RESULTS: We identified 41,248 eligible patients, comprising 1169 in the early ECT group and 40,079 in the control group. After 1:1 propensity score matching, patients in the early ECT group had significantly shorter length of hospital stay than those in the control group (difference: -12.6 days; 95% confidence interval: -17.4 to -7.7 days). There was no significant difference in total hospitalization costs between the 2 groups. Early ECT was not significantly associated with increased in-hospital mortality or fatal adverse events. CONCLUSIONS: Early ECT may reduce length of hospital stay without increasing total hospitalization costs or fatal adverse events in patients with MDD.

BACKGROUND: Little is known about the risk of subsequent cardiovascular events in individuals whose spouse has a history of cardiovascular diseases. We assessed whether the spouse's history of cardiovascular disease is associated with a greater risk of cardiovascular events. METHODS: Using data on married couples from the Japan Medical Data Center database (April 2008-August 2018), we conducted a matched-pair cohort study by matching individuals who had no history of cardiovascular disease and whose spouse had a history of cardiovascular disease at their first health check-up (exposure group) with up to 4 individuals who had no history of cardiovascular disease and whose spouse had no history of cardiovascular disease at their first health check-up (nonexposure group) matched for birth year, sex, and first health check-up year. We compared severe cardiovascular events after the first health check-up between the 2 groups. RESULTS: Among 236 527 eligible married couples (473 054 spouses), we identified 13 759 individuals in the exposure group who were matched with 55 027 individuals in the nonexposure group. During the mean 95-month observational period from the first health check-up, the percentage of individuals with severe cardiovascular events was higher in the exposure group than in the nonexposure group (0.6% [82/13 759] versus 0.4% [224/55 027], respectively), with a hazard ratio of 1.48 (95% CI, 1.15-1.90). Analyses stratified by sex showed that the hazard ratios of the exposure to the spouse's history of cardiovascular disease for severe cardiovascular events in women and men were 1.22 (95% CI, 0.82-1.83) and 1.68 (95% CI, 1.22-2.32), respectively. CONCLUSIONS: This study suggests that a spouse's history of cardiovascular disease can be a risk factor for subsequent cardiovascular events in men but not in women. Further studies are needed to confirm our findings and to explore effective primary prevention strategies for these individuals.

BACKGROUND: Many mechanically ventilated patients in Japan are treated in high-dependency care units (HDUs) rather than intensive care units (ICUs). HDUs can provide intermediate-level care with reduced costs; however, there is limited evidence on whether mechanically ventilated patients should be treated in the ICU or HDU. METHODS: This was a comparative effectiveness study using a nationwide administrative database in Japan. We identified mechanically ventilated patients with pneumonia in ICU or HDU on the day of admission in the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2019. The primary outcome was 30-day in-hospital mortality. Propensity score matching analysis was performed to compare this outcome between patients treated in the ICU and HDU. The robustness of the analyses was evaluated with multivariable regression, overlap weighting, and instrumental variable analyses. FINDINGS: Of 14,859 mechanically ventilated patients with pneumonia, 7,528 (51%) were treated in the ICU and 7,331 (49%) were treated in the HDU. After propensity score matching, patients treated in the ICU had significantly lower 30-day in-hospital mortality than did those treated in the HDU (24.0% vs. 31.2%; difference, -7.2%; 95% confidence interval, -10.0% to -4.4%). The multivariable regression, overlap weighting, and instrumental variable analyses showed a similar direction and magnitude of association. INTERPRETATION: Critical care for mechanically ventilated patients with pneumonia in the ICU was associated with a 7.2% decrease in 30-day in-hospital mortality vs. care in the HDU. Residual confounding may still play a role in the effect estimates. FUNDING: This study received funding from Ministry of Health, Labour and Welfare, Japan, and Ministry of Education, Culture, Sports, Science and Technology, Japan.

Intracardiac echocardiography (ICE) utilized in conjunction with three-dimensional (3-D) mapping systems could enhance ventricular tachycardia (VT) ablation procedures. ICE has been increasingly used in VT ablation; however, the safety and effectiveness of VT ablation under the combined use of ICE remains unclear. The present study aimed to analyze the safety and short-term effects of VT ablation with or without ICE. We retrospectively enrolled patients who underwent initial VT ablation with a combination of ICE and a 3-D mapping system within 3 days of hospitalization and discharged from April 2011 to March 2017 using a nationwide Japanese inpatient database. Following enrollment, we conducted a propensity score-matching analysis to compare safety (in-hospital complications) and effectiveness (readmission within 30 days after discharge due to cardiovascular disease and readmissions within 30 days for repeat VT ablations) between patients who underwent VT ablation with (ICE group) and without ICE (non-ICE group). 3-D mapping systems were applied to both groups. We identified 5,804 eligible patients (1,272 and 4,532 patients in the ICE and non-ICE groups, respectively). One-to-one propensity score matching created a total of 1,147 pairs between the ICE and non-ICE groups. The ICE group showed a significantly lower prevalence of cardiac tamponade than the non-ICE group. There were no significant differences observed between the two groups regarding other outcomes concerning safety and effectiveness. Ventricular tachycardia ablation with ICE used in combination with a 3-D mapping system may reduce cardiac tamponade; however, no additional clinical advantages were noted in terms of safety and effectiveness.

BACKGROUND & AIMS: When physicians start nasogastric tube feeding in mechanically ventilated patients, they have two choices of feeding tube device: a large-bore sump tube or a small-bore feeding tube. Some physicians may prefer to initiate enteral nutrition via the large-bore sump tube that is already in place, and others may prefer to use the small-bore feeding tube. However, it remains unknown whether small-bore feeding tubes or large-bore sump tubes are better for early enteral nutrition. The present study aimed to compare outcomes between these two types of feeding tubes in mechanically ventilated patients. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified adult patients who underwent invasive mechanical ventilation for ≥2 days in intensive care units and received nasogastric tube feeding within 2 days of starting mechanical ventilation. We categorized these patients as receiving early enteral nutrition via small-bore feeding tube (8- to 12-Fr single-lumen tubes) or via large-bore sump tube. Propensity score-matched analyses were performed to compare 28-day in-hospital mortality and hospital-acquired pneumonia between the two groups. RESULTS: A total of 79,656 patients were included. Of these patients, 20,178 (25%) were in the small-bore feeding tube group. One-to-one propensity score matching created 20,061 matched pairs. Compared with those in the large-bore sump tube group, patients in the small-bore feeding tube group had significantly higher 28-day in-hospital mortality (17.0% versus 15.6%; hazard ratio, 1.08; 95% confidence interval, 1.03 to 1.14) and a significantly higher prevalence of hospital-acquired pneumonia (9.3% versus 8.5%; odds ratio, 1.11; 95% confidence interval, 1.02 to 1.21). CONCLUSIONS: This nationwide observational study suggests that small-bore feeding tubes may not be associated with better clinical outcomes but rather with increased mortality and hospital-acquired pneumonia. Because of the uncertainty regarding the mechanism of our findings, further studies are warranted.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, it has remained unknown whether conventional risk prediction tools used in intensive care units are applicable to patients with COVID-19. Therefore, we assessed the performance of established risk prediction models using the Japanese Intensive Care database. Discrimination and calibration of the models were poor. Revised risk prediction models are needed to assess the clinical severity of COVID-19 patients and monitor healthcare quality in ICUs overwhelmed by patients with COVID-19.

BACKGROUND AND AIM: The effect of tranexamic acid (TXA) remains unknown in patients with colonic diverticular bleeding, which is one of the most common causes of lower gastrointestinal bleeding. We investigated the efficacy of TXA for patients with colonic diverticular bleeding. METHODS: We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination database and identified patients who were admitted for diverticular bleeding from 2010 to 2018. Patients who received TXA on the day of admission comprised the TXA group, and the remaining patients comprised the control group. The primary outcome was in-hospital mortality. Secondary outcomes included severe bleeding, blood transfusion within 7 days of admission, length of stay, and hospitalization costs. Propensity score matching was performed to compare outcomes between the two groups. RESULTS: Overall, 78 291 patients met our eligibility criteria, and 30 526 matched pairs were created by one-to-one propensity score matching. After matching, there was no significant difference in in-hospital mortality between the two groups (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.88-1.30); however, TXA administration was associated with significantly lower proportions of severe bleeding events (OR, 0.93; 95% CI, 0.89-0.99), blood transfusions (OR, 0.88; 95% CI, 0.84-0.92), shorter length of stay (difference, -0.23 days; 95% CI, -0.01 to -0.44 days), and lower total hospitalization costs (difference, -$233; 95% CI, -$153 to -$314). CONCLUSIONS: Although TXA was not significantly associated with lower in-hospital mortality, it may reduce severe bleeding, blood transfusions, length of stay, and hospitalization costs.

PURPOSE: Whether intermittent or continuous neuromuscular-blocking agents (NMBAs) would be appropriate during target temperature management (TTM) after cardiac arrest remains unclear. MATERIALS AND METHODS: In this retrospective cohort study, we utilized the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018 and identified patients who received NMBAs during TTM after cardiac arrest on the day of admission. We compared the in-hospital mortality between the propensity-score-matched intermittent and continuous NMBA groups. RESULTS: We identified 5584 eligible patients; 1488 received intermittent NMBAs and 4096 received continuous NMBAs. After propensity score matching, there was no significant difference in the in-hospital mortality between the intermittent and continuous NMBA groups (32.9% vs. 33.1%; odds ratio, 0.98; 95% confidence interval, 0.82-1.18). In subgroup analyses, in-hospital mortality of the continuous NMBA group was significantly higher than that of the intermittent NMBA group in patients aged ≥65 years (p for interaction = 0.021). CONCLUSIONS: This large retrospective study did not suggest that intermittent NMBAs may be inferior to continuous NMBAs in terms of mortality reduction in the overall population receiving TTM for cardiac arrest. However, continuous NMBAs may be inferior to intermittent NMBAs for reducing mortality in elderly patients.

BACKGROUND: For patients with suicide attempts or self-harm, acute-care hospitals often function as the primary or sole point of contact with the healthcare system. However, little is known about patient characteristics or clinical trajectories of suicide attempts and self-harm episodes among those admitted to acute-care hospitals. This study aimed to describe the characteristics of suicide attempts and self-harm among patients admitted to acute-care hospitals, and the clinical practices provided in these hospitals, using a nationwide inpatient database in Japan. METHODS: Using data from the Japanese Diagnosis Procedure Combination inpatient database from June 2015 to March 2017, we identified patients with emergency admission for suicide attempts or self-harm. We did not include patients with elective admission to psychiatric hospitals or outpatients. We described patient characteristics, treatments for physical injuries, psychiatric interventions, and discharge status. RESULTS: We identified 17,881 eligible patients during the 22-month study period. Overall, 38% of the patients did not have any psychiatric or behavioral comorbidities at admission. The most common suicide method was drug overdose (50%), followed by hanging (18%), jumping from a height (13%), cutting or piercing without wrist cutting (7.1%), poisoning (6.6%), and wrist cutting (5.4%). Suicide was completed by 2,639 (15%) patients. Among patients discharged to home, 51% did not receive any psychiatric intervention. In 468 acute-care hospitals (54%), no psychiatric intervention was provided during the study period. CONCLUSION: We found that half of acute-care hospitals did not provide any hospital-based psychiatric care for patients with suicide attempts or self-harm.

Background The most serious complication of bronchial artery embolization (BAE) for hemoptysis is spinal cord infarction. However, because it is rare, previous reports from single institutions have been insufficient to determine the actual prevalence of spinal cord infarction after BAE. Purpose To investigate the actual prevalence of spinal cord infarction as a complication of BAE using a nationally representative inpatient database. Materials and Methods This retrospective study was performed using data from the Japanese Diagnosis Procedure Combination database between July 2010 and March 2018. The authors identified patients who were diagnosed with hemoptysis and underwent BAE during hospitalization. The overall prevalence of spinal cord infarction after BAE was determined. The authors also compared the prevalence of spinal cord infarction using the Fisher exact test according to the embolic agent used for BAE: coils, gelatin sponge (GS) particles, and N-butyl-2-cyanoacrylate (NBCA). Results During the study period, 8563 patients (mean age ± standard deviation, 68 years ± 13; 5103 men) met the inclusion criteria. Among these 8563 patients, 1577 (18%), 6561 (77%), and 425 (5%) underwent BAE with coils, GS particles, and NBCA, respectively. The overall prevalence of spinal cord infarction as a complication of BAE was 0.19% (16 of 8563 patients). The prevalence of spinal cord infarction after BAE with coils, GS particles, and NBCA was 0.06% (one of 1577 patients), 0.18% (12 of 6561 patients), and 0.71% (three of 425 patients), respectively (P = .04). Conclusion With use of a nationwide real-world inpatient database, the results of this study demonstrated that the actual prevalence of spinal cord infarction as a complication of bronchial artery embolization (BAE) for hemoptysis was 0.19%. Patients who underwent BAE with coils had a lower prevalence of spinal cord infarction than patients who underwent BAE with gelatin sponge particles or N-butyl-2-cyanoacrylate. © RSNA, 2021.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) III-j model is widely used to predict mortality in Japanese intensive care units (ICUs). Although the model's discrimination is excellent, its calibration is poor. APACHE III-j overestimates the risk of death, making its evaluation of healthcare quality inaccurate. This study aimed to improve the calibration of the model and develop a Japan Risk of Death (JROD) model for benchmarking purposes. METHODS: A retrospective analysis was conducted using a national clinical registry of ICU patients in Japan. Adult patients admitted to an ICU between April 1, 2018, and March 31, 2019, were included. The APACHE III-j model was recalibrated with the following models: Model 1, predicting mortality with an offset variable for the linear predictor of the APACHE III-j model using a generalized linear model; model 2, predicting mortality with the linear predictor of the APACHE III-j model using a generalized linear model; and model 3, predicting mortality with the linear predictor of the APACHE III-j model using a hierarchical generalized additive model. Model performance was assessed with the area under the receiver operating characteristic curve (AUROC), the Brier score, and the modified Hosmer-Lemeshow test. To confirm model applicability to evaluating quality of care, funnel plots of the standardized mortality ratio and exponentially weighted moving average (EWMA) charts for mortality were drawn. RESULTS: In total, 33,557 patients from 44 ICUs were included in the study population. ICU mortality was 3.8%, and hospital mortality was 8.1%. The AUROC, Brier score, and modified Hosmer-Lemeshow p value of the original model and models 1, 2, and 3 were 0.915, 0.062, and < .001; 0.915, 0.047, and < .001; 0.915, 0.047, and .002; and 0.917, 0.047, and .84, respectively. Except for model 3, the funnel plots showed overdispersion. The validity of the EWMA charts for the recalibrated models was determined by visual inspection. CONCLUSIONS: Model 3 showed good performance and can be adopted as the JROD model for monitoring quality of care in an ICU, although further investigation of the clinical validity of outlier detection is required. This update method may also be useful in other settings.

It is unclear when to begin rehabilitation after coronary artery bypass grafting (CABG) in the intensive care unit (ICU). Using the Japanese Diagnosis Procedure Combination inpatient database from 2010 to 2018, we identified adult patients who underwent a CABG and who were admitted to the ICU for ≥3 consecutive days from the date of their CABG. Patients who started any rehabilitation program prescribed by physicians or therapists within 3 days of CABG were defined as the early rehabilitation group, and the remaining patients were defined as the usual care group. We identified 30,568 eligible patients, with 13,150 (43%) patients in the early rehabilitation group. An inverse probability of treatment weighting analyses showed that the Barthel Index score at discharge in the early rehabilitation group was significantly higher than that in the usual care group (difference: 3.2; 95% confidence interval: 1.5-4.8). The early rehabilitation group had significantly lower in-hospital mortality, total hospitalization costs, length of ICU stay, and hospital stay vs. the usual care group. Our results suggested that early rehabilitation by physicians or therapists beginning within 3 days of CABG was safe, as suggested by the low mortality and improved physical function in patients who underwent CABG.

OBJECTIVE:  The terminal stage of solid tumors sometimes induces disseminated intravascular coagulation (DIC); however, no useful therapeutic strategies have been established. This study investigated the relationship between mortality and recombinant human soluble thrombomodulin (rTM) therapy for patients with DIC associated with stage IV solid tumors using a large nationwide inpatient database. METHODS:  Using the Japanese Diagnosis Procedure Combination Inpatient Database, patients with stage IV solid tumors who developed DIC were identified. Those who received rTM within 3 days of admission were included in the treatment group; the remaining were included in the control group. The primary outcome was the 28-day in-hospital mortality. RESULTS:  Of 25,299 eligible patients, 1 to 4 propensity score matching was used to select 1,979 rTM users and 7,916 nonusers. There was no significant difference in the 28-day mortality (control vs. rTM: 37.4% vs. 34.3%; hazard ratio, 0.95; 95% confidence interval [CI], 0.88-1.04) and critical bleeding rate (control vs. rTM: 3.7% vs. 3.8%; odds ratio, 1.04; 95% CI, 0.75-1.42) between groups. Subgroup analyses showed that the 28-day mortality rate among patients with colorectal and gynecological cancer was significantly lower in the rTM than in the control group (p for interaction 0.033 and 0.010, respectively). CONCLUSION:  Although we identified a possibly beneficial association between rTM administration and mortality in specific populations of patients with colorectal and gynecological cancer, no such association was found when considering the entire cohort of patients with DIC associated with stage IV solid tumors.

OBJECTIVES: The epidemiology of chronic critical illness is not well known. We aimed to estimate the prevalence, mortality, and costs associated with chronic critical illness in Japan. DESIGN: A nationwide inpatient administrative database study in Japan from April 2011 to March 2018. SETTING: Six hundred seventy-nine acute-care hospitals with ICU beds in Japan. PATIENTS: Adult patients who met our definition for chronic critical illness: one of six eligible clinical conditions (prolonged acute mechanical ventilation, tracheotomy, stroke, traumatic brain injury, sepsis, and severe wound) plus at least 8 consecutive days in an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,395,016 ICU admissions during the study period, 216,434 (9.0%) met the definition for chronic critical illness. The most common eligible condition was prolonged acute mechanical ventilation (73.9%), followed by sepsis (50.6%), tracheostomy (23.8%), and stroke (22.8%). Overall inhospital mortality was 28.6%. The overall age-specific population prevalence was 42.0 per 100,000. The age-specific population prevalence steadily increased with age, reaching 109.6 per 100,000 in persons aged greater than 85 years. With extrapolation to national estimates in Japan, there were 47,729 chronic critical illness cases in 2011 and the number remained similar at 46,494 cases in 2017. Hospitalization costs increased gradually, rising from U.S.$2.3 billion in 2011 to U.S.$2.7 billion in 2017. Inhospital mortality decreased from 30.6% to 28.2%, whereas the proportion of patients with total/severe dependence increased from 29.6% to 33.2% and the proportion of patients with decreased consciousness at discharge increased from 18.7% to 19.6%. CONCLUSIONS: Using a nationwide inpatient database in Japan, we found substantial clinical and economic burdens of chronic critical illness in Japan. Chronic critical illness was particularly common in elderly people. Although inhospital mortality of chronic critical illness patients continues to decrease, costs and patients with dependence for activities of daily living or decreased consciousness at discharge are increasing.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

AIM: To develop a procedure-based organ failure assessment model for intensive care unit (ICU) patients and to examine the ability of this model to predict in-hospital mortality, with reference to the Sequential Organ Failure Assessment (SOFA) score. METHODS: Using the Japanese nationwide Diagnosis Procedure Combination database, we identified patients aged ≥15 years who were admitted to the ICUs April 2018-March 2019. Since April 2018, Japanese health care providers have been required to input ICU patients' SOFA scores into this database. We extracted data on the following procedures on ICU admission: oxygen supplementation, invasive mechanical ventilation, blood transfusions, catecholamines, chest compression, extracorporeal membrane oxygenation, and renal replacement therapy. A procedure-based organ failure assessment model (Model 1) for in-hospital mortality was developed using therapeutic procedures for organ failure on the day of ICU admission in the derivation cohort. We also constructed a model using the SOFA score (Model 2). Discriminatory ability was assessed using area under the receiver operating characteristic curve (AUROC) in the validation cohort, and the discriminatory abilities of the models were compared. RESULTS: In total, 69,019 patients were included. Overall in-hospital mortality was 7.2%. The AUROCs for Model 1 (0.810) and Model 2 (0.817) in the validation cohort did not show a statistically significant difference (P = 0.20). CONCLUSION: The models established using procedure-based organ failure assessment showed no statistically significant differences from those using the SOFA score, suggesting that procedure records in administrative databases can be used for risk adjustment in clinical studies on ICU mortality.

AIM: Acute aortic dissection (AAD) has been considered a contraindication for extracorporeal cardiopulmonary resuscitation (ECPR). However, studies are lacking regarding the epidemiology and effectiveness of ECPR for AAD. We aimed to examine whether ECPR for AAD during refractory cardiac arrest is effective. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified all emergently hospitalized adults who received ECPR on the day of admission and all AAD patients who received cardiopulmonary resuscitation on the day of admission. ECPR was defined as receiving both cardiopulmonary resuscitation and percutaneous extracorporeal membrane oxygenation. Outcomes were in-hospital mortality and neurological outcomes. We calculated the incremental cost-effectiveness ratio of ECPR for AAD. RESULTS: We identified 398 AAD patients with ECPR, 9840 non-AAD patients with ECPR, and 9709 AAD patients with cardiopulmonary resuscitation but not ECPR. The incidence of AAD among the patients with ECPR on the day of admission was 3.9%. In-hospital mortality was 98% in AAD patients with ECPR, 79% in non-AAD patients with ECPR, and 98% in AAD patients with cardiopulmonary resuscitation but not ECPR. Seven AAD patients survived to discharge after ECPR; of these, six patients had good neurological outcomes at discharge. The incremental cost-effectiveness ratio of ECPR for AAD was estimated at 161,504 US dollars per quality-adjusted life year gained. CONCLUSION: ECPR successfully improved outcomes and/or facilitated surgery for a small number of AAD patients with refractory cardiac arrest; however, the cost burden of ECPR for AAD patients may be unacceptably high.

INTRODUCTION: Existing evidence on the mortality time trends of patients with disseminated intravascular coagulation (DIC) is limited, and whether the mortality trend or quality of care of DIC patients has improved remains unknown. This study aimed to investigate the temporal trend in mortality, patient outcomes, and treatment preferences of several anticoagulants in Japan. METHODS: This retrospective observational study used the Japanese Diagnosis Procedure Combination inpatient database, which contains data from more than 1200 acute-care hospitals in Japan. We identified all adult patients that were diagnosed with DIC from July 2010 to March 2018 and sorted them into one of five predefined underlying conditions: sepsis, solid cancer, leukemia, trauma, or obstetric. The data collected as general outcomes were the 28-day mortality and major bleeding events. We also evaluated anticoagulant use for DIC treatment. RESULTS: A total of 325,327 DIC patients were included in this study. Regarding the baseline characteristics, an increase in median age, worsened comorbid conditions, and higher illness severity were observed over time. The underlying conditions for DIC were largely unchanged. Over the study period, the 28-day mortality for overall DIC patients decreased from 41.8% (95% CI 41.2%-42.3%) to 36.1% (95% CI 35.6%-36.6%), which is a 14% decrease over the 8-year period (P trend < 0.001). The downward trend in mortality was more evident in patients with sepsis and leukemia (15% and 14% decreases, respectively), whereas no clinically meaningful change in mortality occurred in trauma and obstetrics patients. Over time, major bleeding events modestly increased, and the length of hospital stay decreased. The temporal trend in the treatment preferences of anticoagulants for DIC patients clearly changed over time. CONCLUSIONS: The overall 28-day mortality for DIC patients clearly decreased from 2010 to 2017. The downward trend in mortality might have resulted from the advances made in the fundamental treatment of underlying diseases and from the changes in anti-DIC strategies.

INTRODUCTION: Clinical guidelines state that disseminated intravascular coagulation (DIC) treatment should be based on three clinical phenotypes: the marked bleeding type (e.g. leukemia, trauma, obstetric diseases, or aortic diseases); organ failure type (sepsis or pancreatitis); and asymptomatic type of DIC (solid cancer). However, among the various underlying disorders of DIC, the clinical presentations of bleeding or organ failure have not to date been well documented. The present study aimed to evaluate whether underlying disorders of DIC would affect clinical outcome including death, organ failure, and bleeding. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we identified all adult patients diagnosed with DIC during hospitalization from July 1, 2010, to March 31, 2018. We collected data on patient characteristics and underlying disorders of DIC including sepsis, solid cancer, leukemia, trauma, obstetric diseases, aortic diseases, pancreatitis, and miscellaneous diseases. We counted major bleeding events and calculated an organ failure score for patients during hospitalization. RESULTS: We identified 337,132 patients with DIC. The major disorders underlying DIC were sepsis (42%) and solid cancer (31%). The average organ failure scores of patients with aortic diseases, sepsis, and trauma were 2.8, 2.2, and 2.2, respectively. The percentages with major bleeding events among patients with aortic diseases, trauma, obstetric diseases, and solid cancer were 24%, 15%, 10%, and 10%, respectively. CONCLUSIONS: This study suggests that the clinical presentations of bleeding and organ failure are not associated with the three existing clinical phenotypes of DIC or with the underlying disorders of DIC. Therefore, clinical presentation alone may not be sufficient for identifying the clinical phenotypes of DIC. Further research is necessary to develop new strategies for identifying the phenotypes of DIC and improving treatment strategies for individual patients.

PURPOSE: Patients receiving extracorporeal membrane oxygenation (ECMO) generally receive proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) to avoid major gastrointestinal bleeding. Our aim was to compare outcomes between patients receiving PPIs and H2RAs for stress ulcer prophylaxis during ECMO. MATERIALS AND METHODS: We performed a retrospective cohort study using the Japanese Diagnosis Procedure Combination Database, using data recorded from 1 July 2010 to 31 March 2017. We defined patients who received PPIs within 2 days after starting ECMO as the PPIs group and those who received H2RAs within 2 days after starting ECMO as the H2RAs group. We performed propensity score matching to compare outcomes. The primary outcomes were gastrointestinal bleeding requiring endoscopic haemostasis and in-hospital mortality. The secondary outcomes were red blood cell transfusion, hospital-acquired pneumonia and Clostridium difficile infection during hospitalisation. RESULTS: Of 11 328 eligible patients, 9738 received PPIs and 1590 received H2RAs. Propensity score matching created 1556 pairs. No significant differences were seen regarding endoscopic haemostasis (1.2% vs 0.8%; p=0.37), in-hospital mortality (53.0% vs 53.1%; p=0.94), red blood cell transfusion rates (91.4% vs 89.7%; p=0.11), hospital-acquired pneumonia (13.0% vs 12.4%; p=0.59) or C. difficile infection (0.1% vs 0.2%; p=0.32) between the PPIs and H2RAs groups, respectively. CONCLUSION: We found no differences in the evaluated outcomes between the PPIs and H2RAs groups. Both PPIs and H2RAs are treatment options for stress ulcer prophylaxis in patients undergoing ECMO.

BACKGROUND: Terminal-stage solid tumors are one of the main causes of disseminated intravascular coagulation (DIC); effective therapeutic strategies are therefore warranted. This study aimed to investigate the association between mortality and antithrombin therapy in patients with stage IV solid tumor-associated DIC using a large nationwide inpatient database. METHODS: From July 2010 to March 2018, patients with stage IV solid tumor-associated DIC in the general wards, intensive care unit, or high care unit were identified using the Japanese Diagnosis Procedure Combination Inpatient Database. Patients who received antithrombin within 3 days of admission were allocated to the antithrombin group, while the remaining patients were allocated to the control group. One-to-four propensity score matching analyses were applied to compare outcomes. The primary outcome was the 28-day in-hospital mortality. RESULTS: Of the 25,299 eligible patients, 919 patients had received antithrombin within 3 days of admission and were matched with 3676 patients in the control group. There were no significant differences in the 28-day mortality between the two groups (control vs. antithrombin: 28.9% vs. 30.3%; hazard ratio, 1.08; 95% confidence interval, 0.95-1.23). There were no significant differences in the organ failure score and the proportion of critical bleeding between the two groups. Subgroup analyses showed that the effects of antithrombin were not significantly different among different tumor types. CONCLUSION: Using a nationwide Japanese inpatient database, this study showed that there is no association between antithrombin administration and 28-day mortality in patients with stage IV solid tumor-associated DIC. Therefore, establishing other therapeutic strategies for solid tumor-associated DIC is required.

Objective Carbazochrome sodium sulfonate (CSS) has been routinely used to treat bleeding; however, no study has examined the effect of CSS for gastrointestinal bleeding. Therefore, we aimed to investigate the effect of CSS for colonic diverticular bleeding. Methods We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for diverticular bleeding from July 2010 to March 2018. Patients who received CSS on the day of admission were defined as the CSS group, and those not receiving CSS were defined as the control group. The primary outcome was in-hospital mortality. Secondary outcomes were length of stay, total costs, and blood transfusion within 7 days of admission. Propensity score matching analyses were performed to compare outcomes between the two groups. Results A total of 59,965 patients met our eligibility criteria. Of these, 14,437 (24%) patients received CSS on the day of admission. One-to-one propensity score matching created 14,379 matched pairs. There was no significant difference in the in-hospital mortality between the CSS and control groups (0.6% vs. 0.5%, respectively; odds ratio: 0.96; 95% confidence interval: 0.72-1.29). The length of stay was longer in the CSS group than in the control group (11.4 vs. 11.0 days, respectively; difference: 0.44; 95% confidence interval: 0.14-0.73). There were no significant differences in the total costs or the proportion of patients receiving blood transfusion between the groups. Conclusions CSS may not reduce in-hospital mortality, length of stay, total costs, or the need for blood transfusion in patients with colonic diverticular bleeding.

PURPOSE: For status epilepticus, the choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial: phenytoin or fosphenytoin are recommended, however, it has been unknown which is better. Using a nationwide database, we compared the efficacy and safety of them. METHOD: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from January 1, 2011 through December 31, 2015. Propensity score matching was applied to compare outcomes of the phenytoin and fosphenytoin groups. RESULTS: The analysis examined data of 5265 patients: 2969 patients received phenytoin; 2296 received fosphenytoin, on the day of admission. One-to-one propensity score matching created 1871 matched pairs. No significant difference was found for vasopressor use on the day of admission (4.2 % vs. 4.4 %; odds ratio 1.07; 95 % confidence intervals 0.77-1.48; p = 0.69), or for mechanical ventilation on the day of admission, in-hospital mortality, length of hospital stay, or total hospitalization cost. Higher age, comorbidity of cardiac diseases and lower body mass index were associated significantly with increased vasopressor use, whereas the dose of phenytoin equivalents and the choice of fosphenytoin were not. CONCLUSIONS: This nationwide observational study found no evidence that fosphenytoin provides higher efficacy or safety than phenytoin for treatment of status epilepticus in adults after diazepam. Age, cardiac disease and low body mass index were identified as independent risk factors for vasopressor use in both phenytoin and fosphenytoin.

BACKGROUND: Nationwide data are insufficient with respect to the characteristics of patients undergoing ventricular tachycardia (VT) ablation, complications of VT ablation, and procedure details including catheter devices used during VT ablation. The present study was performed to describe the patient characteristics, procedure details including catheter devices, and in-hospital complications of catheter ablation for VT using a national inpatient database. METHODS: We used the Diagnosis Procedure Combination database, a national Japanese inpatient database, to identify patients who underwent VT ablation from July 2010 to March 2017. We examined patients' age, gender, baseline diseases, comorbid conditions, admission status, catheter devices and drugs used, and in-hospital complications of VT ablation. RESULTS: We identified 10 641 patients (median age, 61 years) who underwent VT ablation. The most frequently observed background heart disease among patients with structural heart disease was ischemic cardiomyopathy. An irrigated ablation catheter was used in 73% of patients, a force-sensing ablation catheter was used in 22%, and intracardiac echocardiography was used in 25%. The frequency of using these procedures continuously increased over time. Overall, the prevalence of in-hospital complications was 3.5% (cardiac tamponade, 0.8%; stroke, 0.6%; critical bleeding, 1.9%; mechanical circulatory support, 0.9%; and in-hospital death, 0.8%). CONCLUSIONS: The results of this study show the clinical features of VT ablation in a real-world clinical setting. The use of irrigated catheters, force-sensing catheters, and intracardiac echocardiography increased over time. The prevalence of in-hospital complications was 3.5%.

OBJECTIVES: Previous studies have suggested that vasodilator therapy may be beneficial for patients with nonocclusive mesenteric ischemia. However, robust evidence supporting this contention is lacking. We examined the hypothesis that vasodilator therapy may be effective in patients diagnosed with nonocclusive mesenteric ischemia. DESIGN: Retrospective cohort study. SETTING: The Japanese Diagnosis Procedure Combination inpatient database. PATIENTS: A total of 1,837 patients with nonocclusive mesenteric ischemia from July 2010 to March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared patients who received vasodilator therapy (vasodilator group; n = 161) and those who did not (control group; n = 1,676) using one-to-four propensity score matching. Vasodilator therapy was defined as papaverine and/or prostaglandin E1 administered via venous and/or arterial routes within 2 days of admission. Only patients who did not receive abdominal surgery within 2 days of admission were analyzed. The main outcomes were in-hospital mortality and abdominal surgery performed greater than or equal to 3 days after admission. After propensity score matching, in-hospital mortality was significantly lower in the vasodilator group (risk difference, -11.6%; p = 0.005). The proportion of patients who received abdominal surgery at greater than or equal to 3 days after admission was also significantly lower in the vasodilator group (risk difference, -10.2%; p = 0.002). CONCLUSIONS: Vasodilator therapy with papaverine and/or prostaglandin E1 is associated with lower in-hospital mortality and prevalence of abdominal surgery in patients with nonocclusive mesenteric ischemia.

Intravenous (i.v.) phenytoin/fosphenytoin is recommended as the second-line therapy of antiepileptic drugs in patients with status epilepticus (SE). i.v. Levetiracetam is regarded as an effective and safe equivalent with i.v. phenytoin/fosphenytoin. However, i.v. levetiracetam is not covered by public health insurance for SE in most countries. For this study, we performed the real-world practice pattern survey of antiepileptic drugs for status epilepticus using the nationwide inpatient database. We used the Japanese Diagnosis Procedure Combination inpatient database in Japan and identified all cases of emergency admission attributable to status epilepticus from March 2011 through March 2018. We described the patient characteristics and practice pattern of antiepileptic drugs. The analysis conducted for this study examined 31,472 cases. As the second-line therapy, the use of i.v. levetiracetam increased rapidly from 2016; 35% of cases received i.v. levetiracetam in 2017. By contrast, the use of i.v. phenytoin/fosphenytoin decreased from 2016. In-hospital mortality decreased year-by-year. No year-by-year change was observed for deaths within 24 h, length of hospital stay, drug-induced hepatitis, or drug-induced eruption. Although the use of levetiracetam for treatment of SE is not compensated by public health insurance in Japan, i.v. levetiracetam use is increasing dramatically as the second-line SE therapy. We propose that health insurance coverage be extended to include i.v. levetiracetam treatment for SE.

BACKGROUND & AIMS: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. METHODS: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 μg/kg/min), medium- (0.1-0.3 μg/kg/min), and high-dose (≥0.3 μg/kg/min) noradrenaline groups. RESULTS: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, -2.9%; 95% confidence interval [CI], -4.5% to -1.3%) and in the medium-dose noradrenaline group (risk difference, -6.8%; 95% CI, -9.6% to -4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, -1.4%; 95% CI, -7.4%-4.7%). CONCLUSIONS: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in those requiring high-dose noradrenaline.

BACKGROUND: Whether enteral nutrition (EN) should be administered early in severe traumatic brain injury (TBI) patients has not been fully addressed. OBJECTIVE: The present study aimed to evaluate whether early EN can reduce mortality or nosocomial pneumonia among severe TBI patients. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2017 linked with the Survey for Medical Institutions, we identified patients admitted for intracranial injury with Japan Coma Scale scores ≥30 (corresponding to Glasgow Coma Scale scores ≤8) at admission. We designated patients who started EN within 2 d of admission as the early EN group, and those who started EN at 3-5 d after admission as the delayed EN group. The primary outcome was in-hospital mortality. The secondary outcome was nosocomial pneumonia. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. RESULTS: We identified 3080 eligible patients during the 36-mo study period, comprising 1100 (36%) in the early EN group and 1980 (64%) in the delayed EN group. After propensity score matching, there was no significant difference in in-hospital mortality (difference: -0.3%; 95% CI: -3.7%, 3.1%) between the 2 groups. The proportion of nosocomial pneumonia was significantly lower in the early EN group than in the delayed EN group (difference: -3.2%; 95% CI: -5.9%, -0.4%). CONCLUSIONS: Early EN may not reduce mortality, but may reduce nosocomial pneumonia in patients with severe TBI.

OBJECTIVE: Focused assessment with sonography in trauma (FAST) examination is a widely known initial evaluation for patients with trauma. However, it remains unclear whether FAST contributes to patient survival in patients with haemodynamically stable trauma. In this study, we compared in-hospital mortality and length of stay between patients undergoing initial FAST vs initial CT for haemodynamically stable torso trauma. METHODS: This was a retrospective cohort study using data from 264 major emergency hospitals in the Japan Trauma Data Bank between 2004 and 2016. Patients were included if they had torso trauma with a chest or abdomen abbreviated injury scale score of ≥3 and systolic blood pressure of ≥100 mm Hg at hospital arrival. Eligible patients were divided into those who underwent initial FAST and those who underwent initial CT. Multivariable logistic regression analysis for in-hospital mortality and multivariable linear regression for length of stay were performed to compare the initial FAST and initial CT groups with adjustment for patient backgrounds while also adjusting for within-hospital clustering using a generalised estimating equation. RESULTS: There were 9942 patients; 8558 underwent initial FAST and 1384 underwent initial CT. Multivariable logistic regression showed no significant difference in in-hospital mortality between the initial FAST and initial CT groups (OR 1.37, 95% CI 0.94 to 1.99, p=0.10). Multivariable linear regression revealed that the initial FAST group had a significantly longer length of stay than the initial CT group (difference: 3.5 days; 95% CI 1.0 to 5.9, p<0.01). CONCLUSIONS: In-hospital mortality was not significantly different between the initial FAST and initial CT groups for patients with haemodynamically stable torso trauma. Initial CT should be considered in patients with haemodynamically stable torso trauma.

INTRODUCTION: Sepsis is a systemic inflammatory response syndrome caused by infectious diseases, with cytokines possibly having an important role in the disease mechanism. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve the outcomes of patients with sepsis through cytokine adsorption. OBJECTIVE: This study aimed to investigate the clinical effect of the AN69ST membrane in comparison to standard continuous renal replacement therapy (CRRT) membranes for panperitonitis due to lower gastrointestinal perforation. METHODS: Using the Diagnosis Procedure Combination database, we identified adult patients with sepsis due to panperitonitis receiving any CRRT. Propensity score matching was used to compare patients who received CRRT with the AN69ST membrane (AN69ST group) and those who received CRRT with other membranes (non-AN69ST group). The primary outcome measure was in-hospital mortality. RESULTS: A total of 528 and 1,445 patients were included in the AN69ST group and in the non-AN69ST group, respectively. Propensity score matching resulted in 521 pairs. There was no significant difference in in-hospital mortality (32.1 vs. 35.5%; p = 0.265) and 30-day mortality (41.3 vs. 42.8%, p = 0.074) between the AN69ST group and the non-AN69ST group. CONCLUSION: There is no significant difference in-hospital mortality between CRRT with the AN69ST membrane and CRRT with standard CRRT membranes for panperitonitis due to lower gastrointestinal perforation. These results indicate that the AN69ST membrane is not superior to the standard CRRT membrane.

AIM: Clinical guidelines for acute lower gastrointestinal bleeding (LGIB) recommend non-endoscopic treatment when endoscopic treatment is difficult or the patient is hemodynamically unstable. The aim of this study was to investigate whether angiography should be prioritized as initial treatment for severe LGIB patients over colonoscopy. METHODS: We undertook a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We compared adult patients who underwent colonoscopy or angiography within 1 day of admission for severe LGIB from 2010 to 2017. The primary outcome was in-hospital mortality. Secondary outcomes included surgery carried out within 1 day after admission and surgery carried out between 2 and 7 days of admission. Propensity score-matched analyses were undertaken to adjust for confounders. RESULTS: We identified 6,546 eligible patients. The patients were divided into the colonoscopy group (n = 5,737) and angiography group (n = 809). After one-to-four propensity score matching, we compared 3,220 and 805 patients who underwent colonoscopy and angiography, respectively. The angiography group was not significantly associated with reduced in-hospital mortality compared with the colonoscopy group. In contrast, the number of patients who underwent surgery within 1 day of admission was significantly lower in the angiography group than in the colonoscopy group. CONCLUSIONS: The present study revealed that in-hospital mortality did not significantly differ between colonoscopy and angiography, even in severe LGIB patients. Although this study was unable to identify which subgroups should undergo angiography for primary hemostasis, angiography might be a better option than colonoscopy for initial hemostasis in more severe cases of LGIB.

Objective: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam vs. fosphenytoin. We compare the safety of intravenous levetiracetam and fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. Methods: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous fosphenytoin on the day of admission were defined as the fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and fosphenytoin groups. Results: The analysis examined data of 5,667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2 vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73-1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the fosphenytoin group (3.2 vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43-0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. Conclusion: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for fosphenytoin, in adult status epilepticus.

AIM: The differences in clinical characteristics between benign asymptomatic and symptomatic pneumatosis intestinalis (PI) remain unknown. This study aimed to reveal the clinical characteristics of PI in critically ill patients. METHODS: This was a retrospective observational study undertaken between 2013 and 2017 in a single facility. Patients with PI were enrolled. Pneumatosis intestinalis was diagnosed using computed tomography, and clinical data were collected. Pathologic PI refers to PI with bowel ischemia. Asymptomatic PI refers to PI with a benign etiology. RESULTS: There were 17 patients with pathologic PI and 31 with asymptomatic PI. Pathologic PI was detected at day 4 of hospital stay, and asymptomatic PI was detected at day 30 of hospital stay (P < 0.01). The symptoms that were different between pathologic and asymptomatic PI were acute diarrhea (18% and 65%, P = 0.01), C-reactive protein level elevation (9.9 and 2.1 mg/dL, P = 0.01), and systemic inflammatory reaction syndrome (100% and 13%, P < 0.01). Computed tomography findings showed a difference in the occurrence of ascites collection (94% versus 23%, P < 0.01) and PI of the ascending colon (47% versus 80%, P = 0.02). Hospital mortality of pathologic PI was 88%, whereas all patients with benign PI survived. The positive likelihood ratio of acute diarrhea with PI of the ascending colon to diagnose benign PI was 7.33 (1.11-48.5). CONCLUSIONS: Pneumatosis intestinalis of the ascending colon that occurs in the post-intensive care phase with a poor inflammatory reaction, acute diarrhea, and no ascites collection could be benign. In other cases, bowel ischemia should be promptly ruled out.

BACKGROUND: Clinical features and complications of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation for Brugada syndrome have not been well studied. METHODS: We used the Japanese Diagnosis Procedure Combination database to retrospectively investigate patients who had undergone ICD implantation between April 2016 and March 2017. We compared the characteristics and in-hospital complications of patients with Brugada syndrome implanted with S-ICD or transvenous (TV)-ICD. RESULTS: We extracted 3090 patients who received ICD implantation. Among them, we identified 278 Brugada patients. The mean age was 43 ± 14.4 years and 262 (94%) were male. Of these 278 patients, 136 (49%) received S-ICD and 142 (51%) received TV-ICD. TV-ICD recipients had a history of atrial fibrillation more frequently compared with S-ICD recipients. The median (interquartile range) of length of hospital stay was not significantly different between patients with S-ICD and TV-ICD (13 days [10-20.5] vs 12 days [10-18], respectively). The prevalence of in-hospital complications after ICD implantation was similar between the two groups. There were no patients with cardiac tamponade, hemothorax, pneumothorax, cardiovascular event, stroke, and death following the procedure during hospitalization in either group. CONCLUSIONS: Short-term safety of S-ICD implantation may be identical to that of TV-ICD. Large prospective studies are warranted to compare the effects and long-term safety of S-ICD compared with TV-ICD.

BACKGROUND: Although tranexamic acid is widely used in patients with haemoptysis, whether it improves mortality has not been well investigated. The aim of this study was to evaluate the effect of tranexamic acid on in-hospital mortality among patients with haemoptysis. METHODS: This was a retrospective study using data from the Japanese Diagnosis Procedure Combination inpatient database. We identified all cases of emergency admission due to haemoptysis from July 2010 to March 2017. Patients were divided into two groups: a control group, and a tranexamic acid group (those who received tranexamic acid on the day of admission). The primary outcome was in-hospital mortality, with secondary outcomes of hospital stay length and total healthcare cost. The data were evaluated using a propensity score matching analysis. RESULTS: Among 28,539 included patients, 17,049 patients received tranexamic acid and 11,490 patients did not. Propensity score analysis generated 9933 matched pairs. Compared to the control group, patients in the tranexamic acid group had significantly lower in-hospital mortality (11.5% vs. 9.0%; risk difference, - 2.5%; 95% confidence interval (CI), - 3.5 to - 1.6%), shorter hospital stays (18 ± 24 days vs. 16 ± 18 days; risk difference, - 2.4 days; 95% CI, - 3.1 to - 1.8 days), and lower total healthcare costs ($7573 ± 10,085 vs. $6757 ± 9127; risk difference, $- 816; 95% CI, $- 1109 to - 523). CONCLUSIONS: Tranexamic acid may reduce in-hospital mortality among patients with haemoptysis requiring emergency admission.

AIM: Patients with accidental hypothermia without vital signs increasingly receive venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, there is limited knowledge regarding the efficacy of this advanced rewarming method. We aimed to determine whether VA-ECMO improved outcomes in patients with accidental hypothermia without vital signs, using a large nationwide inpatient database in Japan. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2017, we identified patients diagnosed with accidental hypothermia who received closed-chest cardiac massage in-hospital on the day of admission. Patients who received VA-ECMO on the day of admission were allocated to the VA-ECMO group, and those who received cardiopulmonary resuscitation (CPR) only were allocated to the conventional CPR group. The primary outcome was in-hospital mortality, and the secondary outcome was a Japan Coma Scale status of "alert consciousness" at discharge. Propensity score-matching analyses were performed to compare the outcomes. RESULTS: We identified 1661 eligible patients during the 81-month study period, and 318 (19%) received VA-ECMO on the day of admission. Crude in-hospital mortality was 65% in the VA-ECMO group and 84% in the conventional CPR group. Propensity score-matching analyses demonstrated significantly lower in-hospital mortality (risk difference: -13%; 95% confidence interval: -21% to -5.1%) and a higher proportion of "alert consciousness" at discharge (risk difference: 8.3%; 95% confidence interval: 1.9%-15%) in the VA-ECMO group compared with the conventional CPR group. CONCLUSION: VA-ECMO was associated with higher survival and favourable neurological outcomes compared with conventional CPR alone in patients with accidental hypothermia without vital signs.

Heatstroke-induced disseminated intravascular coagulation represents potential targets for specific intensive treatments. However, the effect of antithrombin or thrombomodulin treatment remains uncertain. Using a large nationwide inpatient database in Japan, this study aimed to evaluate whether treatment with antithrombin or thrombomodulin could reduce mortality among patients with heatstroke-induced disseminated intravascular coagulation. Using the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2017, we identified heatstroke patients who developed disseminated intravascular coagulation. We allocated patients who started treatment with antithrombin or thrombomodulin within 2 days after admission to the treatment group and allocated others to the control group. A primary outcome was in-hospital mortality. We used a doubly robust analysis to ensure the robustness of our findings. We also conducted two sensitivity analyses for thrombomodulin versus others and antithrombin versus others. We identified 1,606 eligible patients during the 81-month study period. Of these, 556 (35%) received antithrombin or thrombomodulin. The doubly robust analysis demonstrated that in-hospital mortality was significantly lower among patients in the treatment group than among those in the control group (risk difference -6.5%; 95% confidence interval: -12 to -1.4%). In-hospital mortality was significantly lower in patients with thrombomodulin than in others (risk difference -5.5%; 95% confidence interval: -9.5 to -1.6%). There was no significant difference in in-hospital mortality between patients with antithrombin and others (risk difference -4.2%; 95% confidence interval: -9.3 to 0.9%). Treatment with recombinant human thrombomodulin may be associated with lower in-hospital mortality among patients with heatstroke-induced disseminated intravascular coagulation.

OBJECTIVES: Whether enteral nutrition should be postponed in patients undergoing sustained treatment with neuromuscular blocking agents remains unclear. We evaluated the association between enteral nutrition initiated within 2 days of sustained neuromuscular blocking agent treatment and in-hospital mortality. DESIGN: Retrospective administrative database study from July 2010 to March 2016. SETTING: More than 1,200 acute care hospitals covering approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: Mechanically ventilated patients, who had undergone sustained treatment with neuromuscular blocking agents in an ICU, were retrospectively reviewed. We defined patients who received sustained treatment with neuromuscular blocking agents as those who received either rocuronium at greater than or equal to 250 mg/d or vecuronium at greater than or equal to 50 mg/d for at least 2 consecutive days. INTERVENTIONS: Enteral nutrition started within 2 days from the initiation of neuromuscular blocking agents (defined as early enteral nutrition). MEASUREMENTS AND MAIN RESULTS: We identified 2,340 eligible patients during the 69-month study period. Of these, 378 patients (16%) had received early enteral nutrition. One-to-three propensity score matching created 374-1,122 pairs. The in-hospital mortality rate was significantly lower in the early than late enteral nutrition group (risk difference, -6.3%; 95% CI, -11.7% to -0.9%). There was no significant difference in the rate of hospital pneumonia between the two groups (risk difference, 2.8%; 95% CI, -2.7% to 8.3%). Length of hospital stay among survivors was significantly shorter in the early compared with the late enteral nutrition group (risk difference, -11.4 d; 95% CI, -19.1 to -3.7 d). There was no significant difference between the two groups in length of ICU stay or length of mechanical ventilation among survivors. CONCLUSIONS: According to this retrospective database study, early enteral nutrition may be associated with lower in-hospital mortality with no increase in-hospital pneumonia in patients undergoing sustained treatment with neuromuscular blocking agents.

AIM: Use of a physician-manned prehospital emergency medical service (EMS) has recently become widespread in Japan. Understanding the epidemiology of critically ill patients is essential for planning national and regional physician-manned prehospital EMS systems. However, current knowledge on patients receiving physician-manned prehospital EMS is sparse. The present study aimed to determine the clinical features of critically ill patients with and without physician-manned prehospital EMS, using a national inpatient database in Japan. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we identified all hospitalized patients transported to tertiary emergency centers by physician-manned EMS or EMS without a physician from April 2014 to March 2015. We collected data on patient characteristics, in-hospital mortality, admission diagnoses, advanced life support interventions, and incidence of critical illnesses. RESULTS: We identified 497,911 hospitalized patients transported to tertiary emergency centers by EMS. Of these, 15,507 (3%) patients were hospitalized by physician-manned EMS. The majority of admission diagnoses in the physician-manned EMS group were classified "diseases of the circulatory system" (45%) and "injury, poisoning and certain other consequences of external causes" (34%). The rates of in-hospital mortality, advanced life support interventions, and critical illnesses in the physician-manned EMS group were 22%, 51%, and 53%, respectively. The median incidences of hospitalized patients by physician-manned EMS, advanced life support interventions, and critical illnesses were 12, 137, and 205 per 100,000 persons per year in facilities with physician-manned EMS, respectively. CONCLUSION: Our study indicates that physician-manned EMS is dispatched to a relatively small proportion of critically ill patients in Japan.

STUDY DESIGN: Retrospective single-institution observational study. OBJECTIVE: Spinal cord injury (SCI) is associated with a high prevalence of hyponatremia, which can cause various clinical symptoms and increase mortality. We aimed to analyze the risk factors for hyponatremia in patients with acute SCI. SETTING: Trauma Center, Tohoku University Hospital, Japan METHODS: We reviewed the medical records of patients with SCI admitted between January 2008 and November 2016. Least angle regression analyses was performed to assess the association between hyponatremia and other parameters. RESULTS: Of the 213 enrolled patients, 85 (40%) had hyponatremia (serum Na < 135 mmol/L) whilst 19 (9%) had severe hyponatremia (serum Na < 130 mmol/L). Least angle regression analyses revealed that hyponatremia was significantly associated with higher American Spinal Injury Association impairment scale, nosocomial pneumonia, deep vein thrombosis, bradycardia, and surgery for SCI before developing hyponatremia. Severe hyponatremia was significantly associated with traumatic brain injury with an abbreviated injury scale score ≥3, higher American Spinal Injury Association impairment scale, bradycardia, vasopressors, and nosocomial pneumonia. CONCLUSION: Various factors including traumatic brain injury with an abbreviated injury scale score ≥3 and higher American Spinal Injury Association impairment scale may be associated with hyponatremia in patients with acute SCI. These factors can help clinicians identify and monitor SCI patients with a higher hyponatremia risk, and potentially help patients to avoid severe complications.

INTRODUCTION: In contrast to information on the effects of organophosphate, pesticide, or environmental exposures, data on cholinergic crisis caused by pharmaceutical cholinesterase inhibitors are sparse. The present study aimed to describe the characteristics, demographics, and mortality of patients with cholinergic crisis caused by pharmaceutical cholinesterase inhibitors using a nationwide inpatient database in Japan. METHODS: We identified patients diagnosed with cholinergic crisis as a result of taking cholinesterase inhibitor medications in the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2016. We examined the patients' characteristics, treatments, and mortality. RESULTS: A total of 235 patients with cholinergic crisis were identified during the 69-month study period. Forty-eight patients required mechanical ventilation (20.4%), and 15 patients died (6.4%) in hospital. The median lengths of hospital stay and intensive care unit stay were 15 days (interquartile range, 6-42) and 4 days (2-8), respectively. Approximately half of all hospitalized patients required catecholamines, atropine, or mechanical ventilation, while the other half did not require any of these treatments. Patients who required catecholamines, atropine, or mechanical ventilation were more likely to die and had longer hospital stays. CONCLUSIONS: Cholinergic crisis caused by pharmaceutical cholinesterase inhibitors is a rare but potentially life-threatening condition. Patients who require mechanical ventilation and catecholamines or atropine have a poorer prognosis.

PURPOSE: Despite extensive research on enteral nutrition (EN) for patients in shock, it remains unclear whether this should be postponed in patients with cardiogenic or obstructive shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). In this study, we aimed to compare outcomes of early and delayed EN for patients with cardiogenic or obstructive shock requiring VA-ECMO. METHODS: In this retrospective database study drawing on the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2016, we identified patients with cardiogenic or obstructive shock who had received VA-ECMO for more than 2 days. We allocated the patients to two groups: those who received EN within 2 days (early) or 3 days or more (delayed) after starting VA-ECMO. We then used a marginal structural model to analyze associations between early EN and various outcomes, including in-hospital mortality and 28-day mortality. RESULTS: We identified 1769 eligible patients during the 69-month study period, 220 of whom (12%) received early EN. After using a marginal structural model to adjust for baseline and time-dependent confounders, we found that the early EN group showed significantly lower in-hospital mortality [hazard ratio 0.78, 95% confidence interval (95% CI) 0.62-0.98, P = 0.032] and lower 28-day mortality (hazard ratio 0.74, 95% CI 0.56-0.97, P = 0.031) than the delayed EN group. CONCLUSIONS: According to this retrospective database study, early EN is not associated with harm but rather with lower mortality in patients with cardiogenic or obstructive shock requiring at least 2 days of VA-ECMO.

BACKGROUND: The outcomes of multiple injury patients with concomitant torso hemorrhage and traumatic brain injury (TBI) are very poor. The hybrid emergency room system (HERS) is a trauma management system designed to complete resuscitation, computed tomography (CT), surgery, angioembolization, and intracranial pressure (ICP) monitoring all in one trauma resuscitation room without patient transfer. We aimed to review the outcomes of polytrauma patients who underwent concurrent bleeding control and ICP monitoring using the HERS. METHODS: In this retrospective observational study, we enrolled patients who underwent concurrent bleeding control and ICP monitoring using the HERS between August 2011 and June 2018. Initial data on vital signs, Injury Severity Score (ISS), probability of survival (Ps) calculated by the Trauma and Injury Severity Score (TRISS), intervention type, 28-day mortality, and Extended Glasgow Outcome Scale at 6 months after injury were collected. Continuous variables were expressed as the median (25th and 75th percentiles) and categorical variables as numbers (%). RESULTS: Ten patients were included in the analysis. The injury severity of the patients was as high as an ISS of 58 (50-64) and TRISS Ps of 0.15 (0.02-0.36). Seven of the 10 (70%) patients had hemodynamic instability within 30 min from arrival. The recorded durations from arrival to events were CT examination 9 (6-16) min, bleeding control procedure 29 (22-42) min, and neurosurgical intervention 39 (31-53) min. Four of the 10 patients (40%) survived to discharge, and two of them (20%) were able to live independently at 6 months after injury. CONCLUSIONS: The concurrent performance of bleeding control procedure and ICP monitoring would be feasible in HERS settings among polytrauma patients with exsanguinating hemorrhage and TBI.

PURPOSE: The purpose of this study is to investigate the association between a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and neurologic outcome in patients with resuscitation of out-of-hospital cardiac arrest (R-OHCA). MATERIALS AND METHODS: A prospective observational study of adult patients with R-OHCA was conducted. Plasma activity of ADAMTS13 and inflammatory markers, an immunologic marker, and a marker of endothelial damage were measured on admission and day 2. Neurologic outcome was evaluated using the Cerebral Performance Categories on day 90. RESULTS: Plasma activity of ADAMTS13 on day 2 was lower in patients with poor neurologic outcome (n = 18) than that in those with good neurologic outcome (n = 16; P = .008). It was also lower in 28-day nonsurvivors (n = 12) than in survivors (n = 21; P = .019). Soluble thrombomodulin showed a strong correlation with ADAMTS13 (P = .021). Furthermore, ADAMTS13 activity was negatively correlated with the Sequential Organ Failure Assessment score (P < .001), levels of high-mobility group box 1 (P = .028), and levels of interleukin 6 (P = .047) but positively correlated with the monocyte expression of human leukocyte antigen DR (P = .023). CONCLUSION: Decreased ADAMTS13 activity was associated with poor neurologic outcome, high mortality, and worsened immune-inflammatory status in patients with R-OHCA. These results suggest that ADAMTS13 may have pathophysiologic relevance in postcardiac arrest syndrome.