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Background: Dental claims data have been used for epidemiological studies without establishing the validity of the recorded diagnoses or procedures. The present study aimed to examine the accuracy of diagnoses, procedures, operation time, and the number of teeth recorded in dental claims data., Methods: We reviewed the charts of 200 patients who visited and 100 patients who were hospitalized in the Department of General Dentistry, Orthodontics, and Oral and Maxillofacial Surgery in an academic hospital between August 2012 and December 2017. The sensitivity and specificity of the dental claims data for five diseases and 15 procedures were evaluated. We assessed the difference in the number of teeth and duration of general anesthesia between claims data and chart reviews., Results: Sensitivity was more than 86% for six out of seven diagnoses except for pericoronitis (67%). Specificity ranged from 72% (periodontal disease) to 100% (oral cancer for inpatient). The sensitivity of procedures ranged from 10% (scaling for inpatient) to 100%, and the specificity ranged from 6% (food intake on the day of the surgery) to 100%. The mean (standard deviation [SD]) number of teeth in the chart review was 22.6 (6.8), and in the dental claims was 21.6 (8.6). The mean (SD) operation time was 171.2 (120.3) minutes, while the duration of general anesthesia was 270.9 (171.3) minutes., Conclusions: The present study is the first study to validate dental claims data, and indicates the extent of usefulness of each diagnosis and procedure for future dental research using administrative data., (© 2021. The Author(s).)

Objectives: Clinical evidence on prophylactic antibiotics for transarterial chemoembolization (TACE) to prevent liver abscess is limited because liver abscess is a rare event. This study aimed to analyse the association between prophylactic antibiotic use for TACE and the occurrence of liver abscess after TACE., Methods: Using the nationwide Diagnosis Procedure Combination database in Japan, we retrospectively identified patients who underwent TACE for hepatic cancer between July 2010 and March 2017. The primary outcome was liver abscess requiring procedural intervention within 30 days of TACE. Secondary outcomes included 30-day in-hospital mortality and length of stay. Propensity score matching was performed to adjust for potential confounding factors and compare outcomes between patients with and without prophylactic antibiotics., Results: Among 167 544 eligible patients, 134 712 received antibiotics and 32 832 did not. In the matched cohort of 29 211 pairs, the proportion of patients with liver abscess requiring procedural intervention was significantly lower in the antibiotics group than in the no-antibiotics group (0.08% vs. 0.22%, p 0.001; relative risk (95% confidence interval), 0.35 (0.22-0.57); absolute risk reduction, 0.0014 (0.0008-0.0021); and number needed to treat, 696 (476-1223)). There was no significant difference in 30-day in-hospital mortality between the groups. The length of stay was longer in the antibiotics group than in the no-antibiotics group (median, 10 vs. 9 days, p < 0.001)., Conclusions: Prophylactic antibiotic use in patients undergoing TACE was associated with a reduced occurrence of liver abscess requiring procedural intervention., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: While neoadjuvant chemotherapy and chemoradiotherapy (NACRT) for pancreatic head cancer are effective, preoperative endoscopic biliary drainage (EBD) is necessary for managing obstructive jaundice and cholangitis during the preoperative waiting period. Nevertheless, ideal choice of stent type is unclear. We compared plastic stents (PS) and metal stents (MS) in these situations., Methods: We retrospectively studied 43 patients who successfully underwent preoperative EBD prior to NACRT for pancreatic head cancer at a single institution. We divided patients into PS (n = 22) and MS (n = 21) groups. The primary outcome was the rate of re-interventional drainage rate before surgery. Secondary outcomes were rates of EBD-associated and postoperative complications and total costs in the pre- and perioperative periods., Results: The re-intervention rate was significantly greater in the PS group than in the MS group (95% vs 4.8%, respectively, P < 0.05). EBD-associated and postoperative complications were significantly less common in the MS group (P < 0.05). The average total preoperative medical costs were significantly lower in the MS group (PS vs MS: 528,597 vs 395,891 JPY, P = 0.004)., Conclusions: MS can be the first choice for EBD in patients undergoing NACRT for pancreatic head cancer. MS may be less costly overall., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In Japan, the Diagnosis Procedure Combination (DPC) data have been used as a nationwide administrative hospital discharge database for clinical studies. However, few studies have evaluated the validity of recorded diagnoses of cancer in the database., Methods: We compared the DPC data with hospital-based cancer registries in Osaka Prefecture, Japan to assess the validity of the recorded cancer diagnoses in the DPC data. Fifteen types of cancer were included in the analysis. Cancer stage with tumor-node-metastasis (TNM) classification was assessed for eight cancer types with >400 patients. We evaluated concordance and positive predictive value of cancer diagnosis, and concordance of cancer stage between the DPC data and the hospital-based cancer registry., Results: In total, we identified 29,180 eligible patients. The five types of cancer with the highest number of patients were as follows: 6,765 (23.2 %) colorectal, 6,476 (22.2 %) stomach, 4,862 (16.7 %) breast, 4,445 (15.2 %) lung, and 2,257 (7.7 %) liver. Concordance of diagnosis ranged from 63.9 %-99.5 %, and twelve of the fifteen types of cancers had concordance of over 90 %. Positive predictive values of diagnosis ranged from 86.8 %-100 %. Regarding cancer stage, the overall degree of concordance was 67.2 % in all patients and the concordance was over 70 % in four types of cancers., Conclusions: The DPC data had high validity of cancer diagnosis. However, the potential impact of the misclassifications and low concordance in cancer stage among specific type of cancers in the DPC data should be considered., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/aims: To investigate the association between exposure to intraocular pressure (IOP)-lowering medications during pregnancy and neonatal adverse outcomes., Methods: This retrospective, cohort study used the JMDC Claims Database (JMDC, Tokyo, Japan), 2005-2018. We extracted data on pregnant women with glaucoma, including dispensation of (1) any IOP-lowering medications, (2) only prostaglandin analogues (PGs) and 3) only beta-blockers, during the first trimester. We compared frequency of congenital anomalies (CA), preterm birth (PB), low birth weight (LBW) and the composite outcome of these three measures, between the women with and without IOP-lowering medications. We calculated propensity scores (PSs) using logistic regression in which use of IOP-lowering medications was regressed against known confounders (disorders during pregnancy and other chronic comorbidities). We then conducted logistic regression in which neonatal adverse outcomes were regressed against use of IOP-lowering medications with adjustment for the PS., Results: We identified 826 eligible women, 91 (11%) of whom had received any IOP-lowering medications. CA occurred in 9.9% and 6.4%, PB in 2.2% and 4.5%, LBW in 9.9% and 6.0% and composite outcome in 17.6% and 13.3% of mothers with and without IOP-lowering medications, respectively. After adjustment for PS, IOP-lowering medications were not significantly associated with more frequent CA (adjusted OR (aOR), 1.43; 95% CI, 0.66 to 3.12), PB (aOR, 0.45; 95% CI, 0.10 to 1.97), LBW (aOR, 2.11; 95% CI, 0.98 to 4.57) or composite outcome (aOR, 1.40; 95% CI, 0.78 to 2.53). Results were similar regarding PGs only and beta-blockers only., Conclusions: IOP-lowering medications during the first trimester were not significantly associated with increase in CA, PB or LBW., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There is limited evidence on methods to allocate budgets to healthcare providers under capitation schemes. The objective of this study was to construct and test models that predict outpatient visits and expenditure for each healthcare facility using subscriber data from the preceding year., Study Design: We used the database of the Universal Coverage Scheme in Bangkok, Thailand that stores subscriber information and healthcare service utilization data. One-percent and ten-percent random samples of subscribers were selected as training and testing groups, respectively., Methods: Using data of the training group, we constructed a model using a random forest algorithm to predict outpatient visits and expenditure in 2017 from the 2016 data. The model was applied to the testing group and facility-level predicted number of visits and expenditure were compared with actual data., Results: The identically-structured training and testing groups consisted of 37,259 and 371,650 subscribers, respectively. Approximately 25% of subscribers utilized outpatient services. The R 2 for models predicting facility-level utilization rate (visits/subscribers) and expenditure per subscriber in 2017 were 0.85 and 0.75, respectively., Conclusions: The model to predict outpatient visits and expenditure performed well. Such a prediction model may be useful for allocating budgets to healthcare facilities under capitation systems., Competing Interests: HY1 and TJ have academic affiliations with the Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, which is supported by Tsumura & Company. Tsumura & Company played no role in in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to publish the results., (© 2021 The Authors.)

EB-TACE has recently been performed because of its lower hepatotoxicity compared to cTACE in less advanced HCC. However, local recurrence at the tumor margins is often observed after DEB-TACE. cTACE involves filling the intratumoral sinusoids with lipiodol-containing anticancer drugs and accumulating in the drainage area, which is the first site of HCC recurrence. The aim of this study is to evaluate the therapeutic effect of DEB-TACE followed by cTACE in HCC patients. Between 2014 and 2020, 65 patients with Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) of HCC were enrolled and divided into two groups: one group received DEB-TACE followed by cTACE (cTACE group) and the other group received only DEB-TACE (non-cTACE group). Sixty-five patients were medically followed. The median observation time was 14 ± 13.1 months after the first DEB-TACE and outcomes were analyzed for multiple factors. Results: The complete response rate was significantly higher in the cTACE group than in the non-TACE group. The analysis showed that the only factor that increased the CR rate in the cTACE group was the total tumor number (less than four). The OS rate of CR patients was higher than that of non-CR patients in the cTACE group. Adverse events in the cTACE group included severe thrombocytopenia but only in one of twenty-seven patients. Conclusions: The combined therapy with DEB-TACE followed by cTACE may be a new effective therapeutic strategy for the intermediate stage of HCC patients.

Screening and brief interventions have been implemented in primary care settings to reduce excessive drinking. However, the effectiveness of screening and brief interventions within a health checkup setting is unclear. We assessed the effectiveness of general treatment for lifestyle-related diseases following screening for alcohol consumption at health checkups, using data on medical claims and health checkups. Participants were people with excessive drinking who met the threshold of recommendation to receive treatment for lifestyle-related diseases. We analyzed risky drinkers (drinking every day, 40-60 g/day for male and 20-60 g/day for female) and heavy drinkers (drinking every day, >60 g/day) separately. We performed one-to-one propensity score matching between people who received general outpatient treatment for lifestyle-related diseases and those who did not. Outcomes were drinking patterns (frequency and amount) and liver function at the next year's health checkup. Middle-aged males accounted for about 94% of the 23,347 participants. Eleven percent of the participants received treatment after the health checkup. After propensity score matching, among 1990 pairs of risky drinkers, those with treatment were significantly more likely to reduce their frequency of drinking (11.7% vs. 8.7%, p = 0.002) and showed lower transaminase values than those without treatment. In 575 pairs of heavy drinkers, there was no significant change in drinking patterns or liver function. Treatment in primary care after screening at health checkups was associated with the change in drinking behavior and improvement in liver condition among risky drinkers. More intensive intervention may be needed to reduce drinking in heavy drinkers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

It is important to educate caregivers in order to prevent infant injuries. However, there have been few studies on the effects of education on pregnant women. This study aimed to evaluate the effects of injury prevention group education on this group. Study participants were recruited from a group of pregnant mothers attending an antenatal class in Tokyo. Participants were assigned to either the intervention or control group based on the month in which they attended the existing antenatal class. Both groups received a leaflet on injury prevention, but only the intervention group received an additional short one-shot lecture. The implementation of each of the nine safety practices was assessed during home visits after childbirth. Of the 131 study participants (56 in the control group and 75 in the intervention group), 106 (80.9%) received home visits after birth. Mothers in the intervention group implemented three practices significantly more than those in the control group: Keep soft objects away from the baby's head (38.3% vs. 13.0%), Do not place your baby on a high surface (74.6% vs. 52.2%), and Use the baby carrier correctly (93.3% vs. 76.1%). In the future, we plan to follow up the participants to evaluate the program's long-term effects, and to continue to improve the program.

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After i.v. injection of C57BL/6 (H-2 b ) spleen cells into irradiated BDF1 (H-2 b/d ) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5-17. When H-2D d K d transgenic H-2 b lymphoma cells were i.p. inoculated into irradiated, H-2 b splenocyte-transplanted H-2 b/d mice, the infiltration of macrophages cytotoxic against H-2D d K d transgenic H-2 b mouse skin epithelia (a GVHD activity) into the peritoneal cavity preceded several days the infiltration of interleukin (IL)-2-dependent cytotoxic T lymphocytes (CTLs) to achieve a graft-versus-leukemia (GVL) effect. In contrast, allogeneic BM transplanted alone into the irradiated mice did not induce GVHD for 44 days, whereas i.v. injection of graft anti-host macrophages or graft anti-host CTLs along with allogeneic BM, respectively, induced GVHD or promoted the GVL effect in the absence of GVHD. These results revealed that macrophage-induced GVHD and the CTL-mediated GVL effect were a set (Th1: IFN-γ/IL-2) response of the graft to allogeneic hosts and leukemia cells, respectively, and that graft T cell activation rather than inhibition skipped GVHD after BM transplantation.

Aims/introduction: Discontinuation of diabetes care has been studied mostly in patients with prevalent diabetes and not in patients with newly diagnosed diabetes, whose dropout risk is highest. Because enrolling patients in a prospective study will influence adherence, we retrospectively examined whether guideline-recommended practices, defined as nutritional guidance or ophthalmological examination, can prevent patient discontinuation of diabetes care after its initiation., Materials and Methods: We retrospectively identified adults with newly screened diabetes during checkups using a large Japanese administrative claims database (JMDC, Tokyo, Japan) that contains laboratory data and lifestyle questionnaires. We defined discontinuation of physician visits as a follow-up interval exceeding 6 months. We divided the patients into those who received guideline-recommended practices (nutritional guidance or ophthalmology consultation) within the same month as the first visit and those who did not. We calculated propensity scores and carried out inverse probability of treatment weighting analyses to compare discontinuation between the two groups., Results: We identified 6,508 patients with at least one physician consultation for diabetes care within 3 months after their checkup, including 4,574 patients without and 1,934 with guideline-recommended practices. After inverse probability of treatment weighting, patients with guideline-recommended practices had a significantly lower proportion of discontinuation than those without (17.2% vs 21.8%; relative risk 0.79, 95% confidence interval 0.69-0.91)., Conclusions: This study is the first to show that after adjustment for both patient and healthcare provider factors, guideline-recommended practices within the first month of physician consultation for diabetes care can decrease subsequent discontinuation of physician visits in patients with newly diagnosed diabetes., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Little is known about hip fracture inpatient care in East Asia. This study examined the characteristics of patients, hospitals, and regions associated with delivery of hip fracture surgeries across Japan, Korea, and Taiwan. We also analyzed and compared how the resource use and a short-term outcome of the care in index hospitals varied according to factors in the respective health systems., Methods: We developed comparable, nationwide, individual-level health insurance claims datasets linked with hospital- and regional-level statistics across the health systems using common protocols. Generalized linear multi-level analyses were conducted on length of stay (LOS) and total cost of index hospitalization as well as inpatient death., Results: The majority of patients were female and aged 75 or older. The standardized LOS of the hospitalization for hip fracture surgery was 32.5 (S.D. = 18.7) days in Japan, 24.7 (S.D. = 12.4) days in Korea, and 7.1 (S.D. = 2.9) days in Taiwan. The total cost per admission also widely varied across the systems. Hospitals with a high volume of hip fracture surgeries had a lower LOS across all three systems, while other factors associated with LOS and total cost varied across countries., Conclusion: There were wide variations in resource use for hip fracture surgery in the index hospital within and across the three health systems with similar social health insurance schemes in East Asia. Further investigations into the large variations are necessary, along with efforts to overcome the methodological challenges of international comparisons of health system performance., (© 2021. The Author(s).)

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., Competing Interests: This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141). The authors report no potential conflicts of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Surgical procedure for symptomatic spinal metastasis is expected to improve the quality of life. Factors related to short-term perioperative mortality after surgery for spinal metastasis may be different from those related to long-term mortality, which have classically been used to determine the indication for surgery. The purposes of this study were to evaluate factors related to the 30-day mortality after surgery for spinal metastasis and create an integer risk scoring system., Methods: Using the Diagnosis Procedure Combination database from 2010 to 2016, we extracted data of patients who underwent surgical procedure for spinal metastasis. Multivariable logistic regression analysis was performed to clarify the association between patient backgrounds and the 30-day postoperative mortality. We created a risk scoring system using regression coefficients to estimate the 30-day mortality for each patient., Results: Among 3524 patients, the 30-day mortality was 2.6%. Factors associated with a higher 30-day mortality were male sex (odds ratio, 2.50 [95% confidence interval, 1.45-4.31]), emergency admission (1.80 [1.11-2.92]), rapid growth tumors (3.83 [2.49-5.90]), and non-skeletal metastasis (2.27 [1.42-3.64]). In patients with the maximum risk score of five, the 30-day mortality was 16.2%., Conclusions: Factors related to the 30-day mortality were male sex, emergency admission, rapid growth tumors, and non-skeletal metastasis. These findings provide spine surgeons and patients knowledge of the potential risk of short-term perioperative mortality and allow them to consider the risk of surgery., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding the publication of this paper., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Context: Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality., Objective: We aimed to determine the association between infused potassium concentration and in-hospital mortality., Methods: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia., Results: We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further., Conclusion: Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Treatment of latent tuberculosis infection is recommended in patients receiving biologics. However, evidence is weak regarding the efficacy of treatment regimens in this population, and the real-world practice pattern has not been elucidated., Methods: Using a large-scale health insurance claims database in Japan, we identified patients who started treatment of immune-mediated inflammatory diseases with tumor necrosis factor inhibitors or other biologics. Treatment with isoniazid within 12 months of starting a biologic was summarized to evaluate the duration of treatment for latent tuberculosis infection and the time between start of isoniazid and initiation of a biologic., Results: Among 2064 patients starting biologics, 10% received treatment for latent tuberculosis infection with isoniazid. Among the patients with biologics and isoniazid, isoniazid was started in the same month as initiating biologics or 1 month before in 82%. In addition to the recommended 6- and 9-month treatments, 20% of patients were receiving isoniazid at 12 months after starting treatment and 20% received a prescription for 350 days or more., Conclusions: In patients starting biologics, treatment for latent tuberculosis infection was provided for different durations, including not only the recommended periods but also longer periods. Research on safety and effectiveness of the treatment in this population is necessary., Competing Interests: Declaration of competing interest HaY and TJ have academic affiliations with the Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, which is supported by Tsumura & Company. SO has an academic affiliation with the Department of Eat-loss Medicine, Graduate School of Medicine, The University of Tokyo, which is supported by ITO EN. Tsumura & Company and ITO EN played no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to publish the results., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Intraportal injection is regarded as the current standard procedure of hepatocyte transplantation (HTx). In islet transplantation, which shares many aspects with HTx, recent studies have clarified that instant blood-mediated inflammatory reaction (IBMIR), characterized by strong innate immune responses, can cause poor engraftment, so other transplant sites to avoid such a reaction have been established. Although IBMIR was reported to occur in HTx, few reports have evaluated alternative transplant sites for HTx. In this study, we sought to determine the optimum transplant site for HTx. Rat hepatocytes (1.0 × 10 7 ) were transplanted at the 9 transplant sites (intraportal (IPO), intrasplenic (IS), liver parenchyma, subcutaneous, intraperitoneal, renal subcapsular, muscle, inguinal subcutaneous white adipose tissue, and omentum) of analbuminemic rats. The serum albumin levels, immunohistochemical staining (albumin, TUNEL, and BrdU), and in vivo imaging of the grafts were evaluated. The serum albumin levels of the IPO group were significantly higher than those of the other groups ( p < .0001). The BrdU-positive hepatocyte ratio of liver in the IS group (0.9% ± 0.2%) was comparable to that of the IPO group (0.9% ± 0.3%) and tended to be higher than that of the spleen in the IS group (0.5% ± 0.1%, p = .16). Considering the in vivo imaging evaluation and the influence of splenectomy, the graft function in the IS group may be almost entirely achieved by hepatocytes that have migrated to the liver. The present study clearly showed that the intraportal injection procedure is more efficient than other procedures for performing HTx.

Objective Maoto is a traditional Japanese Kampo formula used to treat influenza. However, clinical evidence for maoto has been limited to small-scale studies of its effect in alleviating symptoms. The present study evaluated whether or not the addition of maoto to a neuraminidase inhibitor was associated with a reduction in hospitalization following influenza. Methods Using the JMDC Claims Database, we identified outpatients <60 years old who were diagnosed with influenza by an antigen test from September 2013 to August 2018. One-to-five propensity score matching was conducted between patients who received maoto in addition to a neuraminidase inhibitor and those who received a neuraminidase inhibitor alone. Hospitalization within seven days of the influenza diagnosis was compared in the matched groups using the Mantel-Haenszel test. Results We identified 1.79 million cases of influenza from the database in the 5-year study period. Maoto was prescribed for 3.9% of the 1.67 million cases receiving a neuraminidase inhibitor. In the 64,613 propensity score-matched groups of patients, the 7-day hospitalization rate was 0.116% (n=75) for patients with maoto and 0.122% (n=394) for patients without maoto. The difference between these treatment groups was nonsignificant (common odds ratio, 0.95; 95% confidence interval, 0.74 to 1.22; p=0.695). Conclusion The addition of maoto to a neuraminidase inhibitor was not associated with a decrease in hospitalization among nonelderly patients with influenza. Further research is necessary to clarify the indication and efficacy of maoto.

Background and Aim: Screening for tuberculosis before treating with biologic agents is recommended in patients with immune-mediated inflammatory diseases (IMIDs). We conducted this study to identify adherence to the recommended practice in a real-world setting in Japan., Methods: We used a community-based insurance claims database in a city in the Greater Tokyo Area in Japan. Between July 2012 and January 2019, we enrolled patients with IMIDs in the age range 15 to 74 years who had initiated biologic therapy. Tuberculosis screening was defined as (a) interferon-γ release assay and/or a tuberculin skin test (IGRA/TST) and (b) IGRA/TST and X-ray and/or CT scan (X-ray/CT) within 2 months before starting biologic agents. We analyzed the proportions of patients who underwent tuberculosis screening and their association with the patient- and treatment-related factors and treatment for latent tuberculosis infection (LTBI)., Results: Of 421 patients presumed to have initiated biologic therapy, 202 (48%) underwent IGRA/TST and 169 (40%) underwent IGRA/TST and X-ray/CT. Patients aged 65 to 74 years were more likely to undergo tuberculosis screening than those aged 45 to 64 years. Compared to infliximab, IGRA/TST was less frequently performed in patients treated with etanercept, adalimumab, golimumab, abatacept, and tocilizumab. Treatment for LTBI was provided to 67 (16%) patients. Proportions of patients receiving LTBI treatment did not significantly differ according to the screening status., Conclusion: There was low adherence to the recommendations for tuberculosis screening and prophylactic treatment before biologic therapy. It is necessary to continue alerting clinical practitioners to the importance of screening for tuberculosis and treatment for LTBI., Competing Interests: Hayato Yamana has an academic affiliation with the Department of Health Services Research, Graduate School of Medicine, The University of Tokyo supported by Tsumura & Company. Tsumura & Company played no role in the design of the study, collection, analyses, or interpretation of data, writing of the manuscript, and decision to publish the results. No other authors have any conflicts of interest associated with this article., (© 2020 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Aim: To evaluate the association between cumulative visits for care of minor injuries and risk of traumatic brain injuries in children aged ≤36 months., Methods: We conducted a retrospective analysis of children born from 2009 to 2012, using a health insurance claims database in Japan. We investigated the total number of visits where children aged 0-36 months presented for treatment of minor injuries such as superficial injuries, fractures, burns and foreign body ingestions. Logistic regression analysis was used to evaluate the association between the cumulative number of visits for treatment of minor injuries and traumatic brain injuries in children aged ≤36 months., Results: A total of 91 011 children were included in the analysis, 51% of whom were boys. Traumatic brain injuries were identified in 0.7% of these children. Cumulative visits for care of minor injuries among children aged 0-36 months were significantly associated with traumatic brain injuries by 36 months of age, with an odds ratio of 2.12 (95% confidence interval: 1.68-2.68) for multiple visits., Conclusion: Cumulative visits for treatment of minor injuries during the first 36 months of life were associated with increased risk of traumatic brain injuries by 36 months of age., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: The risks of topical ophthalmic corticosteroids during pregnancy remain unclear. This study investigated the association between exposure to topical ophthalmic corticosteroids during pregnancy and adverse neonatal outcomes., Design: Retrospective, cohort, database study., Methods: Pregnant women with allergic conjunctivitis in the JMDC claims database (JMDC, Tokyo, Japan) between 2005 and 2018 were included. Adverse neonatal outcomes (congenital anomalies [CA], preterm birth [PB], low birthweight [LB], and the composite of these 3 outcomes) were compared between mothers who did and did not receive topical ophthalmic corticosteroids during the first trimester. Controls were women who were not prescribed topical ophthalmic corticosteroids during the first trimester. First, propensity scores were calculated with known confounders, including disorders during pregnancy, other chronic comorbidities, and use of antihistamines. Logistic regression was then conducted with propensity score adjustment., Results: A total of 6,847 eligible women were identified of whom 898 (13%) had received topical ophthalmic corticosteroids. CA occurred in 5.5% and 4.9%, respectively; PB in 3.4% and 3.9%, respectively; LB in 5.9% and 7.0%, respectively; and the composite outcome in 11.7% and 11.7% of unexposed and exposed mothers, respectively. Corticosteroid eye drops were not significantly associated with an increase in CA (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .20); PB (aOR, 1.23; 95% CI, 0.80-1.88; P = .35); LB (aOR, 1.17; 95% CI, 0.84-1.61; P = .35), or composite outcome (aOR, 0.95; 95% CI, 0.73-1.22; P = .68)., Conclusions: The use of topical ophthalmic corticosteroids in pregnant women with allergic conjunctivitis was not associated with any increase in CA, PB, or LB., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective Kampo is a traditional Japanese medicine using formulae of natural agents. Although Kampo is widely practiced, information regarding the current prescriptions of Kampo formulations is lacking. The aim of the study was to describe the outpatient use of Kampo formulations in the current Japanese health insurance system. Methods From the JMDC Claims Database, we identified subscribers with outpatient prescriptions of Kampo extract formulations between April 2017 and March 2018. Prescription records were summarized at the individual level to describe the pattern of each formula's use, such as the frequency of prescription and the number of days within a year that were covered by the prescriptions. We also examined whether or not Kampo formulations were prescribed in combination with other drugs. Results Of the 4.5 million subscribers, 13.5% received prescriptions of Kampo extracts within 1 year, and 54% of Kampo users were women. The most commonly prescribed Kampo formulae included kakkonto, shoseiryuto, and maoto, which were used for the short term covering a median of 5 to 7 days. There were also several formulae that were prescribed for longer periods. The median numbers of days covered by kamishoyosan and keishibukuryogan were 60 and 56, respectively. Kampo formulations were used in combination with Western drugs in 85% of prescriptions. Conclusion Kampo formulations are commonly prescribed under the Japanese insurance system and are frequently used in combination with Western drugs. The pattern of prescriptions varied across different formulae.

Background/aim: Gemcitabine, an inhibitor of DNA synthesis, is the gold standard chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miRNAs) play critical roles in cancers, including PDAC. However, less is known about the effect of gemcitabine on PDAC cells and miRNA expression in PDAC. We evaluated the effect of gemcitabine on the cell cycle of PDAC cells in vitro and in vivo and on the miRNA expression profile., Materials and Methods: Effects of gemcitabine on PK-1 and PK-9 cell growth were evaluated using a cell counting kit-8 assay. Xenografted mouse models were used to assess gemcitabine effects in vivo., Results: Gemcitabine inhibited the proliferation and tumour growth of PK-1 cells, and induced S phase cell cycle arrest. Numerous miRNAs were altered upon gemcitabine treatment of PK-1 cells and xenograft models., Conclusion: Altered miRNAs may serve as potential therapeutic targets for improving the efficacy of gemcitabine in PDAC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cholesterol crystal embolization (CCE) is a rare, mainly iatrogenic condition. The proportion of CCE after cardiovascular procedures has not been fully elucidated. The purpose of this study was to determine the proportion of CCE diagnosed after cardiovascular procedures and to identify risk factors for CCE occurrence. Data on patients aged older than 40 years who underwent cardiovascular procedures between July 2010 and March 2017 were extracted from the Japanese Diagnosis Procedure Combination database. Inpatients diagnosed with CCE within 1 year after procedures in the same hospital were identified. Logistic regression analysis was performed to identify factors associated with the occurrence of CCE. There were 962 patients with CCE in 2,190,300 patients who underwent cardiovascular procedures. The overall proportion of CCE after cardiovascular procedures was 4.4 per 10,000 patients (95% confidence interval 4.1-4.7). The overall in-hospital mortality among patients with CCE was 11% (107/962). Older age, male sex, smoking, heart failure, peripheral vascular disease, cerebrovascular disease, renal insufficiency, diabetes mellitus, hypertension, and aortic aneurism and dissection were significantly associated with the higher occurrence of CCE. Compared with cardioangiography, several procedures were significantly associated with higher occurrence of CCE, including intra-aortic balloon pumping, percutaneous transluminal angioplasty of the renal artery, and transcatheter aortic valve implantation or balloon aortic valvuloplasty. CCE is rare but remains a severe complication of cardiovascular procedures. Atherosclerotic risk factors and certain cardiovascular procedures were associated with CCE.

Gastric cancer is one of the most common malignancies diagnosed worldwide. Telmisartan, an angiotensin receptor blocker (ARB), suppresses the proliferation of cancer cells and the growth of tumors through an unknown mechanism. To identify the mechanism, the present study was designed to evaluate the effects of telmisartan on gastric cancer cell lines and tumors in vitro and in vivo and the associated signaling molecules were identified. It was shown here that telmisartan suppressed the proliferation of the cultured human gastric cancer cell lines MKN74, MKN1 and MKN45 as detected in the CCK‑8 assay. In a mouse xenograft model of gastric cancer, telmisartan suppressed tumor growth by arresting the cell cycle at the G0/G1 phase through inhibition of the expression of cyclin D1, the catalytic subunit of cyclin dependent kinase 4 (CDK4), as well as the phosphorylation of the tumor suppressor retinoblastoma (pRb) protein as detected by western blotting. Notably, telmisartan did not induce apoptosis, as indicated by consistent levels of caspase‑cleaved keratin 18 in MKN74 cells. Furthermore, telmisartan inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and increased the levels of the angiogenesis‑related protein tissue inhibitor of metalloproteinase‑1 (TIMP‑1). Analyses of microarrays revealed that telmisartan altered the expression of miRNAs in MKN74 cells. In conclusion, telmisartan suppressed the proliferation of human gastric cancer cells by inducing cell cycle arrest.

Background: Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary method to identify geriatric conditions among older patients. The aim of the present study was to examine the associations between CGA and short-term outcomes among older adult inpatients with stroke., Methods: The study was a nationwide, retrospective cohort study. We used the Diagnosis Procedure Combination database, a national Japanese inpatient database, to identify older adult stroke patients from 2014 to 2017. The associations between CGA and in-hospital mortality, length of hospital stay, readmission rate, rehabilitation intervention, and introduction of home health care were evaluated using propensity score matching and instrumental variable analysis., Findings: We identified 338,720 patients, 21·3% of whom received CGA. A propensity score-matched analysis of 53,861 pairs showed that in-hospital mortality was significantly lower in the CGA group than in the non-CGA group (3·6% vs. 4·1%, p < 0·001). The rate of long-term hospitalization (> 60 days) was significantly lower in the CGA group than in the non-CGA group (8·7% vs. 10·1%, p < 0·001), and the rates of rehabilitation intervention (30·3% vs. 24·9%, p < 0·001) and home health care (8·3% vs. 7·6%, p  = 0·001) were both higher in the CGA group than in the non-CGA group. Instrumental variable analysis showed similar results., Interpretation: CGA was significantly associated with the examined short-term outcomes. These findings from Japan, one of the most aged countries worldwide, highlight the possible benefits of CGA for short-term outcomes and can be of use for health policy in other international contexts., Funding: This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141)., Competing Interests: We declare no potential conflicts of interest., (© 2020 The Author(s).)

Aim: Previous randomized controlled trials of branched-chain amino acid infusion for hepatic encephalopathy involved a small number of patients, and the effectiveness of branched-chain amino acid infusion has not been clarified. We evaluated whether branched-chain amino acid infusion in addition to lactulose treatment was associated with short-term outcomes in a large population of patients., Methods: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients with hepatic encephalopathy who received lactulose within 2 days of admission from July 2011 to March 2017. We divided the patients into those who received branched-chain amino acid infusion within 2 days of admission in addition to lactulose treatment and those who did not. We conducted propensity-score inverse probability of treatment weighting analyses to compare in-hospital mortality, consciousness at discharge, in-hospital complications, length of stay, and total hospitalization costs between the groups., Results: We identified 8051 patients with hepatic encephalopathy treated with lactulose, including 7560 patients who received lactulose plus branched-chain amino acid infusion and 491 who received lactulose alone. The lactulose plus branched-chain amino acid infusion group had a significantly lower mortality than the lactulose alone group (9.6% vs. 15.0%, odds ratio 0.60, 95% confidence interval 0.44-0.82). The lactulose plus branched-chain amino acid infusion group also had a lower proportion of patients with impaired mental status at discharge, and lower total hospitalization costs than the lactulose alone group., Conclusions: Branched-chain amino acid infusion together with lactulose may improve the prognosis of hepatic encephalopathy., (© 2020 The Japan Society of Hepatology.)

Objective: To examine the age in months at which infants visited outpatient clinics or emergency rooms for the first time for nonfatal injuries and to identify risk factors for the occurrence of these injuries., Study Design: Retrospective cohort study., Methods: We used a health insurance claims database in Japan. Infants born between April 2012 and December 2014 were identified and followed until 12 months of age. We identified their first visit to outpatient clinics or emergency rooms because of nonfatal injuries (wounds/fractures, foreign bodies, and burns). Cox regression analysis was used to examine the association of nonfatal injuries with infants' sex, birth order, and parental age., Results: We identified 46,431 eligible infants. Of these, 7606 (16.4%) were brought to an outpatient clinic or emergency room for nonfatal injuries within 12 months of birth. Of the 7,606, 21.7% were aged ≤4 months and 44.7% ​≤ ​7 months. First-born infants were more likely to have wounds/fractures and burns., Conclusion: One-fifth of first nonfatal infant injuries occurred within 4 months of age. Healthcare providers should provide early education about injury prevention, especially to caregivers of first-born infants., Competing Interests: None declared., (© 2020 The Author(s).)

Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma.

Background/aim: Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms, and therapeutic options for pNETs are limited. Metformin is an anti-hypoglycemic drug that appears to have anticancer effects. However, little is known about the effect of metformin on pNETs. In this study, we investigated the anti-proliferative effect of metformin on a human pNET cell line., Materials and Methods: The anti-proliferative properties of metformin were evaluated in QGP-1 and NCI-H727 cells using a cell counting kit-8 assay. Xenograft mouse models were used to assess the tumor effect in vivo., Results: Metformin inhibited the proliferation and anti-tumor growth of QGP-1 cells, accompanied by their arrest during the cell cycle at the G 0/ G 1 phase. Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array. Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells., Conclusion: Taken together, our study demonstrated the therapeutic potential of metformin and provides molecular mechanistic insights into its anti-tumoral effect on pNETs. This study is the first one describing anti-tumoral effects in pNETs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: We examined the advantages of tubeless percutaneous nephrolithotomy (PCNL) and totally tubeless PCNL over standard PCNL., Materials and Methods: Using a nationwide inpatient database in Japan, we gathered data on patients undergoing PCNL from July 2010 to March 2016 and extracted eligible patients who were candidates for tubeless PCNL. Eligible patients were divided into 4 groups: tubeless, totally tubeless, standard, and standard PCNL with ureteral stent (US). Multivariable analyses compared postoperative hospital stay, duration of analgesic use, urinary tract infection (UTI), and blood transfusion among the 4 groups., Results: Analyses were conducted on patients in the standard (n = 954), tubeless (n = 98), totally tubeless (n = 146), and standard PCNL with US (n = 389) groups. Postoperative hospital stay was significantly shorter in the tubeless group than in the standard group (1.6 days [-2.9 to 0.4]). With reference to the standard PCNL group, there was no significant difference in the number of days of analgesic use or the proportions of postoperative UTIs or blood transfusion among the groups. Postoperative UTIs developed significantly more often in women than in men regardless of the PCNL method., Conclusions: Our multivariable analyses showed that tubeless PCNL was associated with shorter postoperative hospital stays, but totally tubeless PCNL was not., (© 2020 S. Karger AG, Basel.)

Objectives: It is unclear whether mandatory health examination is effective for employees who are already being treated for chronic diseases. We focused on patients being treated for hypertension and evaluated the association between employer-based health examination attendance and diabetes treatment initiation., Methods: Using a database that stores health insurance claims and health examination results of subscribers enrolled in society-managed health insurance plans in Japan, we identified employees aged 40-59 years who were being treated for hypertension when starting diabetes treatment from April 2012 to December 2016. A case-crossover analysis was conducted using 90, 180, and 270 days prior to diabetes treatment initiation as reference points and 90 days after the mandatory health examination as the exposure period. We conducted a subgroup analysis by hemoglobin A1c (HbA1c) level and frequency of outpatient blood glucose testing before the mandatory health examination., Results: We identified 1464 individuals starting treatment for diabetes while on antihypertensive drugs. The overall odds ratio for starting diabetes treatment within 90 days of the health examination was 1.89 (95% confidence interval: 1.70-2.10). The subgroup analysis showed that this odds ratio increased as HbA1c level increased and as blood glucose testing frequency decreased., Conclusions: Among employees starting treatment for diabetes while being treated for hypertension, employer-based mandatory health examination attendance was associated with initiation of diabetes treatment. The health examinations may be functioning as a complement to screening in outpatient settings., (© 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Background: The optimal colloid solution for the treatment of ovarian hyperstimulation syndrome (OHSS) remains to be established., Objective: We aimed to compare artificial colloids (AC) with human albumin (HA) for the treatment of OHSS., Materials and Methods: In this retrospective cohort study, data for OHSS participants were collected from a national inpatient database in Japan. The participants received intravenous fluid management with AC (n = 156) or HA (n = 127). We compared the two groups in terms of the length of stay, development of post-treatment complications, and termination surgery., Results: In multivariable linear regression analyses for log-transformed length of stay with reference to the OHSS participants receiving AC, the regression coefficient (95% confidence interval) in participants receiving HA was 0.03 (-0.04-0.09, p = 0.42). Thromboembolism occurred in two participants in the HA group and three participants in the AC group. Two participants in the HA group suffered renal failure during hospitalization. No participants underwent termination surgery in the two groups., Conclusion: The present results showed comparable efficacy between AC and HA for the treatment of OHSS. There were no significant differences in post-treatment complications between the two groups., Competing Interests: No conflicts of interest are disclosed., (Copyright © 2019 Tetsuji Minami et al.)

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person-years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%-89.3%). This study evaluated the PPV of the algorithm of HBV-DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person-years., (© 2019 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.)

Objectives: Current clinical guidelines discourage long-term prescription of benzodiazepines and Z-drugs (BZD); however, the practice continues to exist. The aim of this study was to investigate the proportion of long-term BZD prescriptions and its risk factors., Design: Retrospective cohort study using a health insurance database., Setting: Japan., Participants: A total of 86 909 patients were identified as outpatients aged 18 to 65 years who started BZD between 1 October 2012 and 1 April 2015. After excluding patients who underwent surgery on the day of first BZD prescription (n=762) and patients without 8 months follow-up (n=12 103), 74 044 outpatients were analysed., Main Outcome Measures: We investigated the proportion of long-term prescriptions for ≥8 months among new BZD users. We assessed patient demographics, diagnoses, characteristics of the initial BZD prescription and prescribers as potential predictors of the long-term BZD prescription. Multivariable logistic regression was performed to assess the association between long-term prescription and potential predictors., Results: Of the new BZD users, 6687 (9.0%) were consecutively prescribed BZD for ≥8 months. The long-term prescription was significantly associated with mood and neurotic disorder, cancer, prescription by psychiatrists, multiple prescriptions, hypnotics and medium half-life BZD in the initial prescription., Conclusion: Despite the recent clinical guidelines, 9% of new BZD users were given prescriptions for more than 8 months. Physicians should be aware of risk factors when prescribing BZDs for the first time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD., Patients and Methods: We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy., Results: Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67-0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference., Conclusion: Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD., Competing Interests: Disclosure TJ (corresponding author), NM, and HY have received financial contributions from Tsumura & Company (Tokyo, Japan) because they have academic affiliations with the Department of Health Services Research, Graduate School of Medicine, The University of Tokyo supported by Tsumura & Company. Tsumura & Company played no role in this study. The corresponding author also receives research funding from Tsumura & Company for research not related to this study. The authors report no other conflicts of interest in this work.

Background: Tracheostomy is often performed in patients with severe burns who are undergoing prolonged mechanical ventilation. However, the appropriate timing of tracheostomy and its effect on mortality remain unknown. The aim of this study was to determine whether tracheostomy can reduce mortality in patients with severe burns., Methods: Using the Japanese Diagnosis Procedure Combination database from April 2010 to March 2014, we extracted data on adult patients with severe burns (burn index score of ≥15) who started mechanical ventilation within 3days of admission. We estimated the hazard ratio for 28-day in-hospital mortality associated with tracheotomy performed from day 5 to 28. We adjusted for baseline and time-dependent confounders using inverse probability of treatment weighting methods and fitted a marginal structural Cox proportional hazard model., Results: We identified 680 eligible patients (94 in the tracheostomy group, 2289 person-days; 586 in the non-tracheostomy group, 11,197 person-days). Patients who underwent a tracheostomy had worse prognostic factors for mortality. After adjustment for these factors, the hazard ratio for 28-day mortality associated with tracheostomy compared with non-tracheostomy was 0.73 (95% confidence interval, 0.39-1.34)., Conclusions: There was no significant association between 28-day in-hospital mortality and early tracheostomy in adult patients with severe burns., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: A reliable scoring system that predicts the walking ability of hip fracture patients would be useful for clinicians. Here we developed a scoring system for hip fracture patients and evaluated its predictive ability., Hypothesis: We hypothesized that age, sex, presence of dementia, walking ability before the injury, fracture type, serum hemoglobin level, serum albumin level and interval in days between admission and surgery would be the predictive factors of the walking ability at discharge., Material and Methods: Data from 409 patients who underwent hip fracture surgery were included. We analyzed factors that affected walking ability and developed a scoring system that predicts the probability of walking unaided or with a cane at discharge., Results: The mean age of the patients was 81.3 years. A total of 164 (40%) patients could walk unaided or with a cane at discharge. Multivariate logistic regression analysis showed that the obstructive factors for the ability to walk unaided or with a cane at discharge were older age (odds ratio [OR]=0.962, p=0.002), dementia (OR=0.126, p<0.001), use of a cane before injury (OR=0.396, p<0.001), trochanteric fracture (OR=0.571, p=0.027) and low serum albumin level (OR=4.15, p<0.001) at admission. The scoring system used the following formula: Score=5-0.04×age+albumin-2(with dementia)- 1(with use of a cane before injury)-1(with trochanteric fracture). The C-statistics for the scoring system was 0.81 (95% confidence interval, 0.77-0.85)., Discussion: This newly developed scoring system of information at admission predicted the discharge mobility of hip fracture patients. In addition to the previously known risk factors, serum albumin level at admission was detected as a new predictor for mobility at discharge., Level of Proof: IV, retrospective study., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 ( N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 ( N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31⁻1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14⁻1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71⁻0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22⁻0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11.

Purpose: Periprosthetic joint infection is a serious complication of total knee arthroplasty. Though there are many factors that might increase its risk, the use of propofol for maintaining general anesthesia could theoretically increase the incidence of infection because of its lipid component that supports bacterial growth. Nevertheless, the relationship between anesthetic maintenance agents and the occurrence of periprosthetic joint infection remains uncertain. The purpose of this study was to compare the incidence of suspected early-onset periprosthetic joint infection between patients undergoing total knee arthroplasty under propofol vs sevoflurane anesthesia., Methods: We conducted a retrospective cohort study of patients in the national inpatient Diagnosis Procedure Combination database in Japan who underwent total knee arthroplasty. Suspected periprosthetic joint infection was surrogately defined as the need for arthrocentesis or debridement within 30 days of surgery. Propensity score matching was performed between patients who received either propofol or sevoflurane for anesthetic maintenance to determine the proportion of those with infection., Results: Eligible patients (n = 21,899) were categorized into either the propofol (n = 7,439) or sevoflurane (n = 14,460) groups. In the 5,140 propensity-matched patient pairs, there was no significant difference in the proportion of arthrocentesis or debridement [1.3% propofol vs 1.7% sevoflurane; respectively (relative risk, 0.76; 95% CI, 0.55 to 1.04; P = 0.10)] between the groups. The mean (SD) length of stay in the propofol group was significantly longer than in the sevoflurane group [32.5 (18.4) days vs 31.4 (14.4) days, respectively; mean difference, 1.1; 95% CI, 0.5 to 1.8; P < 0.001]., Conclusion: Propensity score analysis suggested no significant association between the choice of anesthetic maintenance agent and the occurrence of suspected early-onset periprosthetic joint infection in patients undergoing total knee arthroplasty.

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: Although public reporting of hospital performance is becoming common, it remains uncertain whether public reporting leads to improvement in clinical outcomes. This study was conducted to evaluate whether enrollment in a quality reporting project is associated with improvement in quality of care for patients with acute myocardial infarction., Methods: We conducted a quasi-experimental study using hospital census survey and national inpatient database in Japan. Hospitals enrolled in a ministry-led quality reporting project were matched with non-reporting control hospitals by one-to-one propensity score matching using hospital characteristics. Using the inpatient data of acute myocardial infarction patients hospitalized in the matched hospitals during 2011-2013, difference-in-differences analyses were conducted to evaluate the changes in unadjusted and risk-adjusted in-hospital mortality rates over time that are attributable to intervention., Results: Matching between hospitals created a cohort of 30,220 patients with characteristics similar between the 135 reporting and 135 non-reporting hospitals. Overall in-hospital mortality rates were 13.2% in both the reporting and non-reporting hospitals. There was no significant association between hospital enrollment in the quality reporting project and change over time in unadjusted mortality (OR, 0.98; 95% CI, 0.80-1.22). In 28,168 patients eligible for evaluation of risk-adjusted mortality, enrollment was also not associated with change in risk-adjusted mortality (OR, 0.98; 95% CI, 0.81-1.17)., Conclusions: Enrollment in the quality reporting project was not associated with short-term improvement in quality of care for patients with acute myocardial infarction. Additional efforts may be necessary to improve quality of care.

Aim: In Japan, standard prehospital care is provided by emergency medical services teams. Doctor-staffed ambulances play a role in facilitating the immediate treatment of critically ill patients to increase the survival rates. However, little is known about their activities. We revealed the present situation of doctor-staffed ambulances in Japan., Methods: First, we surveyed all the fire departments in Japan and determined whether a doctor-staffed ambulance was present within their district boundary. Second, we surveyed hospitals that operate doctor-staffed ambulances in their system to list their activities during a 1-week period., Results: Of 133 hospitals that operated a doctor-staffed ambulance, 73 (55%) replied to our questionnaire. Only 26 (36%) of them provided 24-h ambulance deployment. Additionally, 51 (70%) of hospitals bore the operational costs of ambulances. Within 1 week, 345 doctor-staffed ambulances were dispatched, but 97 (28%) were cancelled. In total, 62 patients (28%) were diagnosed with cardiac arrest, 48 (19%) with trauma or burns, 36 (15%) with stroke, and 22 (9%) with acute coronary syndrome; 159 (58%) were transferred to a tertiary emergency medical center., Conclusions: Doctor-staffed ambulances have the advantage of deployment at night and in urban areas compared to doctor-staffed helicopters. Among the 73 hospitals that responded to the questionnaire, doctor-staffed ambulances were dispatched almost as frequently as doctor-staffed helicopters. However, doctor-staffed ambulances did not receive adequate funding. Future data collection is necessary to determine the efficacy of doctor-staffed ambulances among hospitals that operate this service.

Background: There was no established disability predictive measurement for patients with trauma that could be used in administrative claims databases. The aim of the present study was to develop and validate a diagnosis-based disability predictive index for severe physical disability at discharge using the International Classification of Diseases, 10th revision (ICD-10) coding., Methods: This retrospective observational study used the Diagnosis Procedure Combination database in Japan. Patients who were admitted to hospitals with trauma and discharged alive from 01 April 2010 to 31 March 2015 were included. Pediatric patients under 15 years old were excluded. Data for patients admitted to hospitals from 01 April 2010 to 31 March 2013 was used for development of a disability predictive index (derivation cohort), while data for patients admitted to hospitals from 01 April 2013 to 31 March 2015 was used for the internal validation (validation cohort). The outcome of interest was severe physical disability defined as the Barthel Index score of <60 at discharge. Trauma-related ICD-10 codes were categorized into 36 injury groups with reference to the categorization used in the Global Burden of Diseases study 2013. A multivariable logistic regression analysis was performed for the outcome using the injury groups and patient baseline characteristics including patient age, sex, and Charlson Comorbidity Index (CCI) score in the derivation cohort. A score corresponding to a regression coefficient was assigned to each injury group. The disability predictive index for each patient was defined as the sum of the scores. The predictive performance of the index was validated using the receiver operating characteristic curve analysis in the validation cohort., Results: The derivation cohort included 1,475,158 patients, while the validation cohort included 939,659 patients. Of the 939,659 patients, 235,382 (25.0%) were discharged with severe physical disability. The c-statistics of the disability predictive index was 0.795 (95% confidence interval [CI] 0.794-0.795), while that of a model using the disability predictive index and patient baseline characteristics was 0.856 (95% CI 0.855-0.857)., Conclusions: Severe physical disability at discharge may be well predicted with patient age, sex, CCI score, and the diagnosis-based disability predictive index in patients admitted to hospitals with trauma., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Studies on the outcomes of lower limb amputation have been limited by the use of selected study populations and small sample sizes. Although reamputation is an important outcome following lower limb amputation, the risk factors for reamputation remain to be elucidated. The present study was performed to identify risk factors for in-hospital death and reamputation following lower limb amputation., Methods: Using a national inpatient database in Japan, we identified 13,774 patients who underwent lower limb amputation. We examined the patients' backgrounds and employed a multivariable logistic regression analysis to identify factors associated with in-hospital death or reamputation., Results: The average age of the 13,774 patients was 72.4 years, and 63.1% (n=8694) were male. The overall in-hospital mortality rate was 10.8% (1481/13,774). The reamputation rate was 10.1% (782/7779) for patients who initially underwent foot or transtibial amputation (18.2% [391/2148] for foot amputations and 6.9% [391/5631] for transtibial amputations). Multivariable logistic regression analysis revealed higher age, male sex, peripheral vascular disease, use of insulin, hemodialysis, and higher numbers of comorbidities as significant risk factors for reamputation or in-hospital death. Use of hemodialysis was the strongest risk factor (odds ratio, 2.10; 95% confidence interval, 1.87-2.35)., Conclusions: The in-hospital mortality and reamputation rates following lower limb amputation were considerably high, reflecting the severely ill conditions of patients with advanced chronic diseases. Risk factors for in-hospital death and reamputation following lower limb amputation were identified. These should aid surgeons in determining a patient's risk of a poor outcome and deciding on the level of amputation., Competing Interests: CONFLICT OF INTEREST: We have no conflicts of interest to declare., (©2017 The Japanese Association of Rehabilitation Medicine.)

Patients who undergo surgical extirpation of a primary liver carcinoma followed by radiotherapy and chemotherapy leading to complete remission are nevertheless known to develop cancerous metastases 3-10 years later. We retrospectively examined the blood sera collected over 8 years from 30 patients who developed bone metastases after the complete remission of liver cancer to identify serum proteins showing differential expression compared to patients without remission. We detected a novel RGD (Arg-Gly-Asp)-containing peptide derived from the C-terminal portion of fibrinogen in the sera of metastatic patients that appeared to control the EMT (epithelial-mesenchymal transition) of cancer cells, in a process associated with miR-199a-3p. The RGD peptide enhanced new blood vessel growth and increased vascular endothelial growth factor levels when introduced into fertilized chicken eggs. The purpose of this study was to enable early detection of metastatic cancer cells using the novel RGD peptide as a biomarker, and thereby develop new drugs for the treatment of metastatic cancer., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)