Long-term outcomes of stereotactic radiosurgery for intracranial schwannoma in neurofibromatosis type 2: a genetic analysis perspective.

PURPOSE: Neurofibromatosis type 2 (NF2) is intractable because of multiple tumors involving the nervous system and is clinically diverse and genotype-dependent. Stereotactic radiosurgery (SRS) for NF2-associated schwannomas remains controversial. We aimed to investigate the association between radiosurgical outcomes and mutation types in NF2-associated schwannomas. METHODS: This single-institute retrospective study included consecutive NF2 patients with intracranial schwannomas treated with SRS. The patients' types of germline mutations ("Truncating," "Large deletion," "Splice site," "Missense," and "Mosaic") and Halliday's genetic severity scores were examined, and the associations with progression-free rate (PFR) and overall survival (OS) were analyzed. RESULTS: The study enrolled 14 patients with NF2 with 22 associated intracranial schwannomas (median follow-up, 102 months).　The PFRs in the entire cohort were 95% at 5 years and 90% at 10-20 years. The PFRs tended to be worse in patients with truncating mutation exons 2-13 than in those with other mutation types (91% at 5 years and 82% at 10-20 years vs. 100% at 10-20 years, P = 0.140). The OSs were 89% for patients aged 40 years and 74% for those aged 60 years in the entire cohort and significantly lower in genetic severity group 3 than in the other groups (100% vs. 50% for those aged 35 years; P = 0.016). CONCLUSION: SRS achieved excellent PFR for NF2-associated intracranial schwannomas in the mild (group 2A) and moderate (group 2B) groups. SRS necessitates careful consideration for the severe group (group 3), especially in cases with NF2 truncating mutation exons 2-13.

The Effect of Home Care Support Clinics on Hospital Readmission in Heart Failure Patients in Japan.

BACKGROUND: Heart failure is common and is associated with high rates of hospitalization. Home care support clinics/hospitals (HCSCs) and enhanced HCSCs were introduced in Japan in 2006 and 2012, respectively. OBJECTIVE: This study aimed to examine the effect of post-discharge care by conventional or enhanced HCSCs on readmission, compared with general clinics. DESIGN: Retrospective cohort study using the Japanese nationwide health insurance claims database. PARTICIPANTS: Participants were ≥65 years of age, admitted for heart failure and discharged between July 2014 and August 2015 and received a home visit within a month following the discharge (n=12,393). MAIN MEASURES: The exposure was the type of medical facility that provides post-discharge home healthcare: general clinics, conventional HCSCs, and enhanced HCSCs. The primary outcome was all-cause readmission for 6 months after the first visit; the incidence of emergency house calls was a secondary outcome. We used a competing risk regression using the Fine and Gray method, in which death was regarded as a competing event. KEY RESULTS: At 6 months, readmissions were lower in conventional (38%) or enhanced HCSCs (38%) than general clinics (43%). The adjusted subdistribution hazard ratio (sHR) of readmission was 0.87 (95% CI: 0.78-0.96) for conventional and 0.86 (0.78-0.96) for enhanced HCSCs. Emergency house calls increased with conventional (sHR: 1.77, 95% CI:1.57-2.00) and enhanced HCSCs (sHR: 1.93, 95% CI: 1.71-2.17). CONCLUSIONS: Older Japanese patients with heart failure receiving post-discharge home healthcare by conventional or enhanced HCSCs had lower readmission rates, possibly due to compensation with more emergency house calls. Conventional and enhanced HCSCs may be effective in reducing the risk of rehospitalization. Further studies are necessary to confirm the medical functions performed by HCSCs.

Dispensing by Family Pharmacists as a Potential Factor in Pharmacist-initiated Prescription Change: A Retrospective Observational Study.

BACKGROUND: No studies in Japan have examined whether dispensing by family pharmacists, who are incentivized by reimbursement to provide continuous and exclusive medication management, results in prescription changes. Our primary objective was to identify the variables affecting prescription changes, particularly to investigate dispensing by family pharmacists as a possible factor. METHODS: We identified 333,503 records of pharmacy claims data from patients aged 65 years or older who received medication instructions at outpatient pharmacies at Tsukuba, a medium-sized city near Tokyo, between April 2018 and March 2019. We extracted data on dispensing by family pharmacists, number of medicines, patient sex, patient age, and pharmacy category. A multilevel modified Poisson regression analysis was performed to analyze the correlation between dispensing by family pharmacists and pharmacist-initiated prescription change. RESULTS: Dispensing by family pharmacists was 1.37 times more likely to involve a record of prescription change than dispensing by non-family pharmacists. Older age, female sex, polypharmacy, and small-scale pharmacies were also found to be factors. CONCLUSION: This study indicated that dispensing by family pharmacists was a potential factor for pharmacist-initiated prescription changes that may prevent excessive medication and limit pharmacological interactions. Since the likelihood of inappropriate prescriptions being issued varies from hospital to hospital, subsequent studies should take into account the quality of each institution.

Facility staffing associated with potentially avoidable hospitalizations in nursing home residents in Japan: a retrospective cohort study.

BACKGROUND: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan. METHODS: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations. RESULTS: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations. CONCLUSIONS: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors.

How are new drugs disseminated in Japan? Analysis using the National Database of Health Insurance Claims of Japan.

Drug lag refers to the difference in the time of a new drug's approval in different countries; the dissemination of the new drug after approval within the countries is another problem. We examined the nationwide dissemination of 11 cancer drugs approved in Japan between 2011 and 2015 using the National Database of Health Insurance Claims data. We extracted data on the number of cancer drug prescriptions from 47 prefectures and associated demographic information, such as age and sex. Eight diabetes drugs were also examined for comparison. We observed a lag between the marketing approval date of the drugs and their first use. To further explore the rise and pattern of each drug's dissemination, we analyzed the trend of the cumulative number and total of new prescriptions for each prefecture. The results showed that the first month of new cancer drug prescriptions varied across prefectures. On average, they lagged by up to 2 months in the slowest prefectures, whereas the variation was almost nonexistent for diabetes drugs. The patterns of dissemination varied more among cancer drugs across the seven Japanese geographical regions. After the initial prescription, the number of prescriptions showed a steep rise for most cancer drugs, whereas the increase was gradual for diabetes drugs. In conclusion, the dissemination of cancer drugs had a greater lag time than that of diabetes drugs. Further research is needed to explore the causative factors to ensure that all effective drugs are equally accessible for those who need them.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Related Microglial Activation in Neonatal Hypoxic-Ischemic Encephalopathy: Morphologic Consideration.

Neonatal hypoxic-ischemic encephalopathy (nHIE) is a major neonatal brain injury. Despite therapeutic hypothermia, mortality and sequelae remain severe. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with the pathophysiology of nHIE. In this study, morphologic change and microglial activation under the nHIE condition and LOX-1 treatment were investigated. The microglial activity and proliferation were assessed with a novel morphologic method, immunostaining, and quantitative PCR in the rat brains of both nHIE model and anti-LOX-1 treatment. Circumference ratio, the long diameter ratio, the cell area ratio, and the roundness of microglia were calculated. The correlation of the morphologic metrics and microglial activation in nHIE model and anti-LOX-1 treated brains was evaluated. LOX-1 was expressed in activated ameboid and round microglia in the nHIE model rat brain. In the evaluation of microglial activation, the novel morphologic metrics correlated with all scales of the nHIE-damaged and treated brains. While the circumference and long diameter ratios had a positive correlation, the cell area ratio and roundness had a negative correlation. Anti-LOX-1 treatment attenuated morphologic microglial activation and proliferation, and suppressed the subsequent production of inflammatory mediators by microglia. In human nHIE, round microglia and endothelial cells expressed LOX-1. The results indicate that LOX-1 regulates microglial activation in nHIE and anti-LOX-1 treatment attenuates brain injury by suppressing microglial activation.

Hospitalizations for Ambulatory Care Sensitive Conditions in a Large City of Japan: a Descriptive Analysis Using Claims Data.

BACKGROUND: Hospitalization for ambulatory care sensitive conditions (ACSCs) is an indicator of the quality of primary care in different health systems. In Japan, where patients can choose any healthcare facility with universal health coverage (UHC), data on these admissions are unknown. OBJECTIVE: To describe the current situation of ACSC admissions in a city of Japan. DESIGN: Retrospective observational study using claims data. PARTICIPANTS: Beneficiaries aged 0-74 years of the National Health Insurance (NHI) program in a large city in the Greater Tokyo Area. We extracted ACSC admissions from all inpatient claims between April 2013 and March 2017. MAIN MEASURES: We calculated age- and sex-specific annual ACSC admission rates for three categories: acute, chronic, and vaccine-preventable. We estimated the age-adjusted admission rates by ACSC category according to administrative districts and rate ratios using Poisson regression models. We also estimated medical expenditures and lengths of stay for ACSC admissions. KEY RESULTS: Of 91,350 hospitalization episodes, we identified 7666 (8.4%) that were ACSC admissions. Males had higher annual ACSC admission rates than females (p < 0.001), especially for chronic ACSCs. Admission rates were lowest in those aged 15-39 years and higher in the youngest (0-4 years) and oldest (70-74 years) age groups. Age-adjusted chronic ACSC admission rates were lower in a newly developed area (rate ratio [RR]: 0.79, 95% confidence interval [CI]: 0.71-0.87) and higher in a residential area (RR: 1.14, 95% CI: 1.04-1.24) than in the center of the city. Total medical expenditures for all ACSC admissions accounted for 5.8% of the total inpatient expenditures of NHI in the city. CONCLUSIONS: ACSC admission rates in Japan were higher for males than for females and showed a U-shaped trend in terms of age, as in other countries with UHC, and deferred by region. This study provided possible factors to reduce ACSC admissions.

Influence of the COVID-19 Pandemic on Overall Physician Visits and Telemedicine Use Among Patients With Type 1 or Type 2 Diabetes in Japan.

BACKGROUND: Regular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of the novel coronavirus 2019 (COVID-19) in Japan and to assess whether telemedicine contributed to continued visits. METHODS: We used the JMDC Claims database, which contains the monthly claims reported from July 2018 to May 2020 and included 4,595 (type 1) and 123,686 (type 2) patients with diabetes. Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019. RESULTS: For patients with type 1 diabetes, the estimates for total overall physician visits were -2.53 (95% confidence interval [CI], -4.63 to 0.44) in April and -8.80 (95% CI, -10.85 to -6.74) in May; those for telemedicine visits were 0.71 (95% CI, 0.47-0.96) in April and 0.54 (95% CI, 0.32-0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were -2.50 (95% CI, -2.95 to -2.04) in April and -3.74 (95% CI, -4.16 to -3.32) in May; those for telemedicine visits were 1.13 (95% CI, 1.07-1.20) in April and 0.73 (95% CI, 0.68-0.78) in May. CONCLUSION: The COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilization of telemedicine among patients with diabetes during April and May 2020.

Predicting factors of clinically significant urological anomalies after initial urinary tract infection among 2- to 24-month-old children.

AIM: To find more effective criteria to identify clinically significant urological anomalies after initial urinary tract infection among children. METHODS: Children aged 2-24 months with an initial urinary tract infection were consecutively recruited in a Japanese hospital from 2013 to 2019. Voiding cystourethrography, 99mTc dimercaptosuccinic acid scan and ultrasound were intended to perform for all cases. Clinically significant urological anomalies were defined as high-grade vesicoureteral reflux, obstructive and abnormal urinary tract lesions, need for surgical intervention, renal hypoplasia and scarring. Using classification and regression tree analysis, we sought the associated factors. We developed new criteria with these factors, retrospectively applied them to the original data, and calculated the sensitivity and specificity. RESULTS: One hundred sixty-seven patients were eligible, and 39 had clinically significant urological anomalies. Classification and regression tree analysis showed that the associated factors were non-E. coli infections, serum creatinine levels and ultrasound abnormalities. When the gold standards were performed on children with non-E. coli infections or serum creatinine levels ≥0.21 mg/dl, sensitivity and specificity were 0.82 and 0.68, respectively. CONCLUSION: The criteria including non-E. coli infections and high-normal or higher serum creatinine levels may efficiently predict clinically significant urological anomalies after initial urinary tract infections.

Adherence to Daily, Weekly, and Monthly Dosing Regimens of Bisphosphonates for Osteoporosis Treatment in Postmenopausal Women in Japan: A Retrospective Study Using Claims Data.

Poor medication adherence of osteoporosis patients is a major global medical problem because of its negative impact on health outcomes and quality of life. The aim of this study was to evaluate how differences in dosing regimens influence adherence to oral bisphosphonates using data from a large health insurance provider in Japan. This was a retrospective observational study using claims data obtained between October 2012 and January 2018, from the community-based National Health Insurance program of a large city in Japan. The data included in the analysis were obtained from women 60 to 74 years old whose oral bisphosphonate prescription was detected between April 2013 and February 2017. Treatment adherence was monitored from the initial prescription for one year, i.e., up to January 2018. Primary comparisons among the daily-dosing, weekly-dosing, and monthly-dosing groups were based on the mean medication possession ratio (MPR). Data from a total of 3,958 patients were analyzed. The numbers of patients aged 60-64, 65-69, and 70-74 were 425, 1,400, and 2,133, respectively. The highest mean MPR was 69.4% for the monthly-dosing of bisphosphonates, followed by the weekly-dosing at 63.5%, and daily-dosing at 57.2%. Using the Kruskal-Wallis test with Dunn-Bonferroni correction, there were significant differences in mean MPR for daily versus weekly (p < 0.01), daily versus monthly (p < 0.001), and weekly versus monthly dosing regimens (p < 0.05). These results suggest significantly more patients adhere to a monthly or weekly regimen of bisphosphonates in the treatment of osteoporosis than to a daily regimen.

[Use of simulation models in health economic evaluation studies of dietary salt-reduction policies for cardiovascular disease prevention].

Objectives　Social security costs related to the healthcare and long-term care of patients with cardiovascular diseases is a national burden that is expected to grow as Japan's population ages. Nutritional policies for improving the nation's diet could prevent cardiovascular diseases, but scientific evidence on their costs and outcomes is limited. This study gives an overview of health economic evaluation studies on population-wide dietary salt-reduction policies that have been instituted for the purposes of cardiovascular disease prevention. Thus, this study provides background information for the development of evaluation methods that can be utilized in Japan for analyzing the effects of nutritional policies on public health and social security cost containment.Methods　We extracted representative health economic simulation models that are used for predicting the effects of cardiovascular disease-related interventions: Cardiovascular Disease Policy Model, IMPACT Coronary Heart Disease Policy and Prevention Model, US IMPACT Food Policy Model, Assessing Cost-Effectiveness (ACE) approach to priority-setting, and Prevention Impacts Simulation Model (PRISM). Next, we collected original articles on studies that used these models for assessing the costs and effects of national population-wide dietary salt-reduction policies. We then outlined the background, structure, and applied studies associated with each model.Results　The five models utilized Markov cohort simulation, microsimulation, proportional multistate life tables, and system dynamics to predict the effect of dietary salt-reduction policies on blood pressure reduction and cardiovascular disease prevention. The models were applied to countries such as Australia, England, and the United States to simulate long-term (10 years to lifetime) costs and effects. These applied studies examined policies that included health promotion campaigns, sodium labels on the front of food packages, and mandatory or voluntary reformulation by the food industry to reduce the salt content of processed foods.Conclusion　Health economic simulation modeling is actively being used to evaluate scientific evidence on the costs and outcomes of national dietary salt-reduction policies. Similarly, leveraging simulation modeling techniques could facilitate the evaluation and planning of dietary salt-reduction policies and other nutritional policies in Japan.

Antithrombotic strategies after transcatheter aortic valve implantation: Insights from a network meta-analysis.

OBJECTIVES: We aimed to investigate the efficacy and safety of different antithrombotic strategies in patients undergoing transcatheter aortic valve implantation (TAVI) using network meta-analyses. BACKGROUND: Meta-analyses comparing single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT), ± oral anticoagulant (OAC) was conducted to determine the appropriate post TAVI antithrombotic regimen. However, there was limited direct comparisons across the different therapeutic strategies. METHODS: MEDLINE and EMBASE were searched through December 2018 to investigate the efficacy and safety of different antithrombotic strategies (SAPT, DAPT, OAC, OAC + SAPT, and OAC + DAPT) in patients undergoing TAVI. The main outcome were all-cause mortality, major or life-threatening bleeding events, and stroke. RESULTS: Our search identified 3 randomized controlled trials and 10 nonrandomized studies, a total of 20,548 patients who underwent TAVI. All OACs were vitamin K antagonists. There was no significant difference on mortality except that OAC + DAPT had significantly higher rates of mortality compared with others (p < .05, I2 = 0%). SAPT had significantly lower rates of bleeding compared with DAPT, OAC+SAPT, and OAC+DAPT (hazard ratio [HR]: 0.59 [0.46-0.77], p < .001, HR: 0.58 [0.34-0.99], p = .045, HR: 0.41 [0.18-0.93], p = .033, respectively, I2 = 0%). There was no significant difference on stroke among all antithrombotic strategies. CONCLUSION: Patients who underwent TAVI had similar all-cause mortality rates among different antithrombotic strategies except OAC+DAPT. Patients on SAPT had significantly lower bleeding risk than those on DAPT, OAC + SAPT, and OAC + DAPT. Our results suggest SAPT is the preferred regimen when there is no indication for DAPT or OAC. When DAPT or OAC is indicated, DAPT + OAC should be avoided.

Trauma complications and in-hospital mortality: failure-to-rescue.

BACKGROUND: Reducing medical errors and minimizing complications have become the focus of quality improvement in medicine. Failure-to-rescue (FTR) is defined as death after a surgical complication, which is an institution-level surgical safety and quality metric that is an important variable affecting mortality rates in hospitals. This study aims to examine whether complication and FTR are different across low- and high-mortality hospitals for trauma care. METHODS: This was a retrospective cohort study performed at trauma care hospitals registered at Japan Trauma Data Bank (JTDB) from 2004 to 2017. Trauma patients aged ≥ 15 years with injury severity score (ISS) of ≥ 3 and those who survived for > 48 h after hospital admission were included. The hospitals in JTDB were categorized into three groups by standardized mortality rate. We compared trauma complications, FTR, and in-hospital mortality by a standardized mortality rate (divided by the institute-level quartile). RESULTS: Among 184,214 patients that were enrolled, the rate of any complication was 12.7%. The overall mortality rate was 3.7%, and the mortality rate among trauma patients without complications was only 2.8% (non-precedented deaths). However, the mortality rate among trauma patients with any complications was 10.2% (FTR). Hospitals were categorized into high- (40 facilities with 44,773 patients), average- (72 facilities with 102,368 patients), and low- (39 facilities with 37,073 patients) mortality hospitals, using the hospital ranking of a standardized mortality rate. High-mortality hospitals showed lower ISS than low-mortality hospitals [10 (IQR, 9-18) vs. 11 (IQR, 9-20), P < 0.01]. Patients in high-mortality hospitals showed more complications (14.2% vs. 11.2%, P < 0.01), in-hospital mortality (5.1% vs. 2.5%, P < 0.01), FTR (13.6% vs. 7.4%, P < 0.01), and non-precedented deaths (3.6% vs. 1.9%, P < 0.01) than those in low-mortality hospitals. CONCLUSIONS: Unlike reports of elective surgery, complication rates and FTR are associated with in-hospital mortality rates at the center level in trauma care.

Risk Factors and Outcomes of Cerebral Stroke in End-Stage Renal Disease Patients Receiving Hemodialysis.

OBJECTIVE: Dialysis patients have a higher incidence of stroke, and outcomes are often poor. Diabetic nephropathy (DN) is a stroke risk-factor, but the importance is unclear in dialysis patients. This study investigated the stroke features and risk factors in hemodialysis (HD) patients. METHODS: All end-stage renal disease patients undergoing HD at Teraoka Memorial Hospital dialysis center were identified, with 195 recruited. Baseline clinical characteristics were collected, and the clinical outcomes and related factors of stroke in HD patients were retrospectively analyzed. The incidence rate of stroke and mortality were calculated using Kaplan-Meier survival analysis. Factors potentially related to stroke were analyzed by the log-rank test and Cox proportional hazards model for univariate and multivariate analysis. RESULTS: In total, 21.0% (41 of 195) patients developed stroke. The incidence rates of stroke per 1000 patient-years were 53.6, 65.2, and 34.0 in all HD patients, DN patients, and non-DN patients, respectively. The cumulative incidence rates of stroke in all HD patients, DN patients, and non-DN patients per 5 years, and per 10 years were 22.6%, 43.5%; 28.8%, 59.6%; and 17.6%, 31.1%, respectively. The incidence rate of stroke in the DN patients was significantly higher than in the non-DN patients (P = .013). DN was the significant risk factor for stroke by multivariate analysis (hazard ratio 2.63, 95% confidence interval 1.08-7.85; P = .032). CONCLUSIONS: This study revealed the trends of stroke in HD patients at a single institution in Japan. DN was shown to be a significant risk factor for stroke in HD patients.

A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival. RESULTS: sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value. CONCLUSION: sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission.

BACKGROUND: Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. METHODS: This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. RESULTS: Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). CONCLUSIONS: Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Contribution of Diabetes to the Incidence and Prevalence of Comorbid Conditions (Cancer, Periodontal Disease, Fracture, Impaired Cognitive Function, and Depression): A Systematic Review of Epidemiological Studies in Japanese Populations.

BACKGROUND: Several epidemiological studies have determined the relationship between diabetes and the incidence and/or prevalence of recently identified comorbid conditions (cancer, periodontal disease, fracture, cognitive impairment, and depression). These relationships may vary by country or race/ethnicity. We aimed to systematically review studies in this field conducted with the Japanese population because such a review in the Japanese population has never been undertaken. METHODS: We conducted systematic literature searches in PubMed and Ichushi-Web databases for studies published until December 2016. Studies comparing the incidence and/or prevalence of the comorbidities among the Japanese population were included. The studies were classified as integrated analyses, cohort studies, case-control studies, or cross-sectional studies. RESULTS: We identified 33 studies (cancer: 17, periodontal disease: 5, fracture: 5, cognitive impairment: 4, and depression: 2). Although several cohort studies and meta-analyses had assessed the development of cancer in diabetes, there was scant epidemiological evidence for the other conditions. Indeed, only one cohort study each had been conducted for periodontal disease, fracture, and cognitive impairment, whereas other evidence was cross-sectional, some of which was induced from baseline characteristic tables of studies designed for other purposes. CONCLUSION: In Japan, there is insufficient evidence about the relationship between diabetes and the incidence/prevalence of periodontal disease, fracture, cognitive impairment, and depression. By contrast, several cohort studies and integrated analyses have been conducted for the relationship with cancer. Further studies should be undertaken to estimate the contribution of diabetes on the incidence/prevalence of comorbidities that may be specific to the Japanese population.

Is Whole-Body CT Associated With Reduced In-Hospital Mortality in Children With Trauma? A Nationwide Study.

OBJECTIVES: We aimed to investigate whether whole-body CT for children with trauma is associated with a different mortality than only selective CT. DESIGN: A multicenter, retrospective cohort study. SETTING: Nationwide trauma registry from 183 tertiary emergency medical centers in Japan. PATIENTS: We enrolled pediatric trauma patients less than 16 years old who underwent whole-body CT or selective CT from 2004 to 2014. INTERVENTIONS: We classified the patients into a whole-body CT group if they underwent head, chest, abdomen, and pelvis CT and a selective CT group if they underwent at least one, but not all, of the above scans. MEASUREMENTS AND MAIN RESULTS: We analyzed data from 9,170 eligible patients (males, 6,362 [69%]; median age, 9 yr [6-12 yr]). Of these, 3,501 (38%) underwent whole-body CT. The overall in-hospital mortality was 180 of 9,170 (2.0%), that of patients who underwent whole-body CT was 102 of 3,501 (2.9%), and that of patients who underwent selective CT was 78 of 5,669 (1.4%). After adjusted multilevel logistic regressions and propensity score matching, the whole-body CT group demonstrated no significant difference in terms of in-hospital mortality compared with the selective CT group. The adjusted odds ratios (whole-body CT vs selective CT) for in-hospital mortality were as follows: multilevel logistic regression model 1 (1.05 [95% CI, 0.70-1.56]); multilevel logistic regression model 2 (0.72 [95% CI, 0.44-1.17]); propensity score-matched model 1 (0.98 [95% CI, 0.65-1.47]); and propensity score-matched model 2 (0.71 [95% CI, 0.46-1.08]). Subgroup analyses also revealed similarities between CT selection and in-hospital mortality. CONCLUSIONS: In this nationwide study, whole-body CT was frequently used among Japanese children with trauma. However, compared with the use of selective CT, our results did not support the use of whole-body CT to reduce in-hospital mortality. Selective use of imaging may result in less radiation exposure and provide more benefits than whole-body CT to pediatric trauma patients.

Risk-Stratified Incidence of Renal Replacement Therapy Initiation: A Longitudinal Analysis Using Medical Claims and Health Checkup Data.

Intervention for higher-risk participants of health checkups especially with diabetes has been started in Japan to prevent renal replacement therapy (RRT) initiation, but evidence about RRT initiation risk among checkup participants has been scarce. To estimate the incidence by risk factors, we conducted a retrospective cohort study using medical claims and checkup data of a community-based insurance scheme in Japan. Beneficiaries who participated in the checkup in 2012-2013 were included and followed up for about five years. We estimated the incidence of RRT initiation by the subject characteristics, followed by investigation for risk factors in bivariate analyses and multivariable regression analyses with Bayesian prior probability distributions. As a result, among 49,252 participants, 37 initiated dialysis (0.21/1,000 person-years); no kidney transplantation was performed during the period. Baseline estimated glomerular filtration rate was strongly associated with dialysis initiation. No dialysis was initiated among those without baseline hypertension; cumulative incidence by hypertension status was significantly different (p < 0.001). Diabetes was significantly associated with dialysis initiation in bivariate analysis, but the association was not significant in multivariable regression analysis [reference: no diabetes; incidence rate ratio (IRR) for diabetes without medication, 3.30 (95% credible interval, 0.48-15.56); IRR for diabetes with medication, 1.69 (95% credible interval, 0.68-3.47)]. In conclusion, potential risk factors for RRT initiation include male sex, comorbid hypertension, and current smoking status, in addition to advanced chronic kidney disease, proteinuria, and diabetes. New initiatives should consider these factors to increase the efficacy of the programs at the population level.