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Objectives: Although amoxicillin is the first-line prophylactic drug for impacted mandibular third molar extraction, third-generation cephalosporins are widely prescribed in Japan. The lack of real-world evidence may be one reason for this inappropriate use. We evaluated differences in the incidence of surgical site infection between amoxicillin and third-generation cephalosporins for impacted mandibular third molar extraction., Methods: Using the JMDC Claims Database, we identified dental visits with fully or horizontally impacted mandibular third molar extraction from April 2015 to March 2020. One-to-one propensity-score matching was conducted between amoxicillin and third-generation cephalosporin groups. The incidence of surgical site infection following extraction was compared in the matched pairs using McNemar's test., Results: We identified 109,266 dental visits, including 39,514 (36.2%) patients who received amoxicillin and 69,752 (63.8%) patients who received third-generation cephalosporins. In the 39,514 matched pairs, the incidence of surgical site infection was 3.5% (n = 1399) for amoxicillin group and 3.7% (n = 1467) for third-generation cephalosporin group (p = 0.003)., Conclusions: Amoxicillin was associated with a lower incidence of surgical site infection after impacted mandibular third molar extraction compared with third-generation cephalosporins. This result supports current guidelines and strengthens the importance of disseminating and implementing antimicrobial resistance control in dentistry., (© 2022 Wiley Periodicals LLC.)

Background: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations., Methods: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated., Results: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models., Conclusion: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Introduction: The association between the use of cilostazol as a post-stroke antiplatelet medication and a reduction in post-stroke pneumonia has been suggested. However, whether cilostazol has a greater preventive effect against post-stroke aspiration pneumonia (AP) than other antiplatelet medications remains unclear. Thus, this study aimed to evaluate whether cilostazol has a greater preventive effect against post-stroke AP than aspirin or clopidogrel., Methods: Through the Japanese Diagnosis Procedure Combination database, we identified patients who were hospitalized for ischemic stroke between April 2012 and September 2019. We performed 1:1 propensity score matching between patients who received cilostazol alone at discharge and those who received aspirin or clopidogrel alone at discharge. The primary outcome was the 90-day readmission for post-stroke AP. The occurrence of recurrent ischemic stroke within 90 days was also evaluated., Results: Among the 305,543 eligible patients with ischemic stroke, 65,141 (21%), 104,157 (34%), and 136,245 (45%) received cilostazol, aspirin, and clopidogrel, respectively. Propensity score matching generated 65,125 pairs. The cilostazol group had a higher proportion of 90-day post-stroke readmissions with AP than the aspirin or clopidogrel groups (1.5% vs. 1.2%, p < 0.001). The proportion of patients with recurrent ischemic stroke within 90 days was also higher in the cilostazol group (2.4% vs. 2.2%, p = 0.017)., Conclusion: The present study suggests that cilostazol may not have a greater effect on preventing post-stroke AP within 90 days than other antiplatelet medications. Nevertheless, further randomized controlled trials with longer follow-up periods are warranted., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Anti-glomerular basement membrane (anti-GBM) disease is treated with immunosuppressive medications and plasma exchange. However, whether plasma exchange, in addition to pulse glucocorticoid therapy, would benefit patients with anti-GBM disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage remains unclear., Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients diagnosed with anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage from July 2010 to March 2020. We compared in-hospital mortality within 10 days of hospitalization between patients who received therapeutic plasma exchange in addition to pulse glucocorticoid therapy and those who received pulse glucocorticoid therapy alone. Overlap weighting based on propensity score was performed to adjust for potential confounders., Results: We identified 207 eligible patients; 168 patients received therapeutic plasma exchange plus pulse glucocorticoid therapy, while 39 patients received pulse glucocorticoid therapy alone. The mean dose of therapeutic plasma exchange was 52.2 ml/kg/day of albumin and/or fresh frozen plasma. Therapeutic plasma exchange in addition to pulse glucocorticoid therapy was associated with a lower in-hospital mortality risk in the unweighted (10.7% versus 28.2%; risk difference, 17.5%; 95% confidence interval, 2.6-32.4%; P = 0.02) and weighted analyses (11.5% versus 28.4%; risk difference, 17.0%; 95% confidence interval, 1.5-32.5%; P = 0.03) than pulse glucocorticoid therapy alone., Conclusions: This retrospective cohort study using a national database suggests that therapeutic plasma exchange may improve the in-hospital prognosis of anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflicts of interest in relation to the work presented in the manuscript.

Objectives: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing pneumonia in older adults remains controversial. Some studies have suggested differences in their effectiveness according to age or sex., Methods: We conducted an observational study using a database of vaccine subsidization data and health insurance claims for a city in Japan. Participants were residents from 2014 to 2018 turning 65, 70, 75, 80, 85, 90, or 95 years during a given fiscal year, and PPV23 during the first year of observation were identified. We matched vaccinated and non-vaccinated individuals of the same age using propensity scores for vaccination. The incidence of hospitalization with pneumonia was compared using the Fine-Gray regression model. We summarized the results for each age using random-effects meta-analysis and conducted a subgroup analysis by sex., Results: A total of 102 136 participants were included, of whom 35% received PPV23. Propensity score matching selected 32 510 pairs of vaccinated and non-vaccinated individuals. Overall, PPV23 administration was associated with a decreased incidence of hospitalization with pneumonia (17.2 vs. 20.4 per 1000 person-years, sub-distribution hazard ratio: 0.84, 95% CI: 0.77 to 0.91). Vaccine effectiveness was the highest among those aged 70 years and decreased with increasing age. No statistically significant effect was observed in those aged 90 or 95 years. Vaccine effectiveness was observed in both males and females., Conclusions: PPV23 was associated with an overall decrease in hospitalization with pneumonia in older adults. However, vaccine effectiveness was significant in those aged 65 to 85 years but not in the older population., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Large-scale administrative health care databases are increasingly being utilized for research. However, there has not been much literature that validated administrative data in Japan; a previous review identified six validation studies published between 2011 and 2017. We conducted a literature review of studies that assessed the validity of Japanese administrative health care data., Methods: We searched for studies published by March 2022 that compared individual-level administrative data with a reference standard from another data source, as well as studies that validated administrative data using other data within the same database. The eligible studies were also summarized based on characteristics which included data types, settings, reference standard used, numbers of patients, and conditions validated., Results: There were 36 eligible studies, including 29 that used external reference standard and seven that validated administrative data using other data within the same database. Chart review was the reference standard in 21 studies (range of the numbers of patients, 72-1674; 11 studies conducted in single institutions and nine studies in 2-5 institutions). Five studies used a disease registry as the reference standard. Diagnoses of cardiovascular diseases, cancer, and diabetes were frequently evaluated., Conclusions: Validation studies are being conducted at an increasing rate in Japan, although most of them are small scale. Further large-scale comprehensive validation studies are necessary to effectively utilize the databases for research., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database., Methods: Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups' baseline patient characteristics and treatments were compared., Results: The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child-Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis., Conclusions: HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice., (© 2023. The Author(s).)

Background: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database., Methods: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined., Results: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals., Conclusions: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination., Design: Matched cohort and self-controlled case series (SCCS) studies., Participants: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events., Methods: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods., Main Outcome Measures: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis., Results: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively., Conclusions: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Although there have been studies that compared outcomes of patients with acute myocardial infarction (AMI) across countries, little focus has been placed on institutional variance of outcomes. The aim of the present study was to compare institutional variance in mortality following percutaneous coronary intervention (PCI) for AMI and factors explaining this variance across different health systems., Methods: Data on inpatients who underwent PCI for AMI in 2016 were obtained from the National Health Insurance Data Sharing Service in Korea, the Diagnosis Procedure Combination (DPC) Study Group Database in Japan, and the National Health Insurance Research Database (NHIRD) in Taiwan. Multilevel analyses with inpatient mortality as the outcome and the hierarchical structure of patients nested within hospitals were conducted, adjusting for common patient-level and hospital-level variables. We compared the intraclass correlation coefficient (ICC) and the proportion of variance explained by hospital-level characteristics across the three health systems., Results: There were 17 351 patients from 160 Korean hospitals, 29 804 patients from 660 Japanese hospitals, and 10 863 patients from 104 Taiwanese hospitals included in the analysis. Inpatient mortality rates were 6.3%, 7.3%, and 6.0% in Korea, Japan, and Taiwan, respectively. After adjusting for patient and hospital characteristics, Taiwan had the lowest variation in mortality (ICC, 1.8%), followed by Korea (2.2%) and then Japan (4.5%). The measured hospital characteristics explained 38%, 19%, and 9% of the institutional variance in Korea, Taiwan, and Japan, respectively., Conclusion: Korea, Japan, and Taiwan had similarly uniform outcomes across hospitals for patients undergoing PCI for AMI. However, Japan had a relatively large institutional variance in mortality and a lower proportion of variation explainable by hospital characteristics, compared with Korea and Taiwan., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: It remains unclear which factors contribute to dysphagia recovery after an acute stroke. This study aimed to identify factors associated with complete oral intake recovery in patients with post-stroke dysphagia., Methods: Data were obtained from the Diagnosis Procedure Combination database, which is a nationwide database of administrative claims and discharge abstracts in Japan. We selected patients admitted within 3 days of stroke onset and conducted multivariable logistic regression analysis. Total oral intake within 30 days of admission was the primary outcome measure., Results: A total of 151,302 patients were included, and total oral intake was observed in 48% of them within 30 days of admission. Total oral intake was significantly associated with age, sex, stroke subtype, consciousness disturbance, low body mass index, multiple comorbidities, and the modified Rankin Scale before stroke onset. In addition, males had worse outcomes than females (odds ratio, 0.75; 95% confidence interval, 0.73-0.77, p < 0.001), and intracerebral and subarachnoid hemorrhagic stroke subtypes were associated with non-recovery., Conclusion: This study identified several prognostic factors for total oral intake in patients with acute stroke. These results may be useful for predicting a patient's dysphagia prognosis at the time of admission and designing a nutritional management plan for patients with acute stroke., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Renal failure and hepatic cirrhosis are mutually aggravating factors. However, no specific therapeutic strategies for hepatic encephalopathy (HE) and end-stage kidney disease have been established. The coexistence, with an extremely poor prognosis, makes randomized controlled trials unfeasible. We evaluated whether an infusion of branched-chain amino acids was associated with mortality in patients hospitalized for HE and end-stage kidney disease., Design and Methods: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with HE and end-stage kidney disease who received hemodialysis 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 and those who did not. We conducted analyses using overlap weights based on propensity scores to compare in-hospital mortality between the groups. Sub-group analysis was conducted by stratifying patients by Child-Pugh class., Results: We identified 553 eligible patients, including 503 patients who received branched-chain amino acid infusion and 50 who did not. The patients who received branched-chain amino acid infusion had lower mortality than those who did not (10.2% vs. 20.1%, relative risk 0.51, 95% confidence interval 0.27-0.95). Sub-group analysis showed that branched-chain amino acid infusion was associated with decreased in-hospital mortality in patients with Child-Pugh class C (16.2% vs. 39.0%, relative risk 0.41, 95% confidence interval 0.23-0.76)., Conclusions: Branched-chain amino acid infusion may improve the prognosis of HE in patients with end-stage kidney disease, particularly those with lower liver function. Further research is necessary to provide a suitable treatment for HE in patients with end-stage kidney disease., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Polypharmacy and its adverse drug events are a major healthcare challenge related to falls, hospitalisations and mortality. Comprehensive geriatric assessment (CGA) may contribute to polypharmacy improvement, however, there is no clear evidence so far., Methods: Using a national inpatient database in Japan from April 1, 2014 to March 31, 2018, we investigated the association between CGA and polypharmacy. We identified patients aged ≥65 years admitted for ischaemic stroke who could receive oral medications. Propensity score matching was conducted for patients with and without CGA during hospitalisation. The outcomes were polypharmacy (defined as use of five or more types of oral medications) at discharge, the number of medication types prescribed at discharge, and the difference between the numbers of medication types prescribed on admission and at discharge., Findings: A total of 162,443 patients were analysed, of whom 39,356 (24·2%) received CGA, and propensity score matching identified 39,349 pairs. Compared with non-CGA group, the CGA group had a significantly lower proportion of polypharmacy at discharge (34·3% vs. 32·9%, p  < 0·001) and a smaller number of medication types prescribed at discharge (3·84 vs. 3·76, p  < 0·001)., Interpretation: This study shows the clear evidence that there is a positive relationship between CGA and a reduction in the number of medications in older inpatients with ischaemic stroke., Funding: The Ministry of Health, Labour and Welfare, Japan and the Ministry of Education, Culture, Sports, Science and Technology, Japan., Competing Interests: All authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© 2022 The Author(s).)

Objective: To investigate the association between exposure to topical ophthalmic antibiotics during pregnancy and adverse neonatal outcomes., Methods: In this retrospective cohort study, we identified pregnant women with hordeola, chalazia, blepharitis, or bacterial conjunctivitis from 2005 to 2018 using the Japanese Medical Data Centre Claims Database. From the eligible women, we extracted women who were dispensed no topical antibiotics during the first trimester (non-antibiotic group), women who were dispensed topical fluoroquinolones alone at least once (fluoroquinolone alone group), and women who were dispensed any single type of antibiotic (single-antibiotic group). We compared the frequency of congenital anomalies (CA), preterm birth (PB), low birth weight (LBW), and the composite outcome of these three between the fluoroquinolone and non-antibiotic groups and between the single-antibiotic and non-antibiotic groups, using propensity score adjustment., Results: A total of 891 eligible women were identified. In the fluoroquinolone (n = 409) and non-antibiotic (n = 309) groups, CA occurred in 6.8% and 6.8%, PB in 2.4% and 3.2%, LBW in 2.9% and 3.2%, and the composite outcome in 10.5% and 11.3%, respectively. Analysis using propensity score adjustment showed no significant difference between the groups in the frequency of CA (adjusted odds ratio, 1.15; 95% confidence interval, 0.61-2.18), PB (0.80; 0.30-2.17), LBW (1.08; 0.45-2.63), or the composite outcome (1.12; 0.67-1.87). Comparison of the single-antibiotic and non-antibiotic groups showed similar results., Conclusions: Topical ophthalmic antibiotics for hordeola, chalazia, blepharitis, or bacterial conjunctivitis during the first trimester were not associated with increased adverse neonatal outcomes., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: To describe patterns in antibiotic prophylaxis for tooth extraction following the 2016 Japanese National Action Plan on Antimicrobial Resistance., Methods: Using a health insurance claims database, we retrospectively identified tooth extraction visits by patients aged ≥18 years from September 2015 to August 2018 and classified patients as undergoing extraction of a fully impacted or horizontally impacted mandibular wisdom tooth, being at risk of infective endocarditis or surgical site infection, or being at low risk. Antibiotic use and type of antibiotics prescribed on the day of tooth extraction were evaluated across the study period, with stratification by tooth extraction category and facility type (hospital or dental clinic)., Results: We identified 662,435 patients with tooth extraction. The mean age was 42.7 years, and 57% were male. Twelve percent underwent wisdom tooth extraction, 32% were high risk, and 10% visited hospitals. The proportion of antibiotic use was 83% overall and 82% among low-risk patients. This proportion remained similar throughout the study period. A shift from third-generation cephalosporins to amoxicillin was observed from 2015 to 2018: the proportion prescribed third-generation cephalosporins decreased from 58% to 34% in hospitals and from 57% to 56% in clinics, and the proportion prescribed amoxicillin increased from 16% to 37% in hospitals and from 6% to 10% in clinics., Conclusions: The pattern of prophylactic antibiotic use for tooth extraction gradually changed after the initiation of the National Action Plan. Further efforts are required to reduce potentially inappropriate prescriptions for low-risk patients, especially in dental clinics., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.)

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).)

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.)

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).)

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.)

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.

Introduction: To develop and validate a new trauma mortality prediction scoring system based on International Statistical Classification of Diseases (ICD)-10 codes, using a Japanese administrative claims and discharge abstract database., Methods: This retrospective observational study used the Japanese Diagnosis Procedure Combination database. Injuries were categorised into 33 groups with 5 additional groups based on injury sites and types. A multivariable logistic regression analysis was performed for in-hospital mortality in a derivation cohort after adjusting for the 38 groups, patient's sex, age and Charlson Comorbidity Index score. Each variable was assigned a score that was equal to the value of the regression coefficient. The new severity score was defined as the sum of the scores. The new scoring system was tested in a validation cohort., Results: The mortality rates were 2.4% (9270/393 395) and 2.5% (8778/349 285) in the derivation and validation cohorts, respectively. The area under the receiver operating curve (AUROC) of the new scoring system was 0.887 (95% CI 0.884 to 0.890) in the validation cohort. Subgroup analyses showed that the scoring system retained high predictive performance both for patients <65 years (AUROC 0.934, 95% CI 0.928 to 0.939) and for elderly patients at the age of ≥65 years (AUROC 0.825, 95% CI 0.820 to 0.829)., Conclusions: A new ICD-10-based injury severity scoring system was developed and validated. Further studies are required to validate the scoring system in other databases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: Sivelestat is widely used in Japan for the treatment of acute respiratory distress syndrome caused by pneumonia. Although the efficacy of sivelestat was reported in several Japanese studies in the early 2000 s, a multinational randomized control trial did not support these findings. We therefore conducted the present study to examine the association between the use of sivelestat and mortality in pneumonia patients requiring mechanical ventilation., Methods: We conducted a retrospective observational study using the Diagnosis Procedure Combination database, a national inpatient database in Japan. We identified pneumonia patients requiring mechanical ventilation who were hospitalized between April 2012 and March 2014. Propensity score matching was performed to compare 7- and 30-day mortality between patients with and without sivelestat use., Results: The eligible patients (n = 16,471) were categorized into the sivelestat (n = 1707) and control (n = 14,764) groups. The unmatched comparison showed significant differences between the sivelestat and control groups in both 7-day mortality (11.0 vs. 7.6%, p < 0.001) and 30-day mortality (29.9 vs. 19.7%, p < 0.001). In the 1516 pairs of propensity-matched patients, there were no significant differences in 7-day mortality (sivelestat vs., Control: 10.2 vs. 10.9%, p = 0.516) and 30-day mortality (sivelestat vs. control 29.0 vs. 29.0%, p = 1.000)., Conclusions: The propensity-matched analyses revealed that the use of sivelestat was not associated with decreased mortality for pneumonia patients requiring mechanical ventilation.

Background and Objective: Although oral care may have salutary effects among frail elderly people, access to dental care is often limited in long-term care facilities. In 2009, the Japanese long-term care insurance system introduced an additional reimbursement scheme for enhanced oral care supervised by dentists in nursing facilities. The aim of this study was to examine whether enhanced oral care provided by trained nursing facility staff members is sufficient to improve health outcomes among nursing facility residents., Design, Setting, and Participants: This was a quasi-experimental study using a nationwide long-term care database. Using facility-level propensity score matching, we identified 170,874 residents in 742 facilities that provided enhanced oral care and 167,546 residents in 742 control facilities that provided only standard care from 2009 to 2012. We used a resident-level difference-in-differences approach to analyze the impact of enhanced oral care on health outcomes among nursing facility residents., Results: After controlling for resident characteristics and background time trends, no significant differences were found between residents admitted to the facilities with and without enhanced oral care in the incidence of critical illness, transfer to a hospital, mortality, or costs. Yearly change in the odds of discharge to home was significantly increased for residents with enhanced oral care (odds ratio = 1.07; 95% confidence interval: 1.02-1.12; P = .008)., Conclusion: The results suggest that enhanced oral care provided by trained nursing facility staff members may improve the general condition of elderly residents in nursing facilities and promote their discharge to home., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Diagnoses recorded in administrative databases have limited utility for accurate identification of severe sepsis and disseminated intravascular coagulation (DIC). We evaluated the performance of alternative identification methods that use procedure records., Methods: We obtained data for adult patients admitted to intensive care units in three hospitals during a 1-year period. Severe sepsis and DIC were identified by three means: laboratory data, diagnoses, and procedures. Using laboratory data as a reference, the sensitivity and specificity of procedure-based methods and diagnosis-based methods were compared., Results: Of 595 intensive care unit admissions, 212 (35.6%) and 81 (13.6%) were identified as severe sepsis and DIC, respectively, using laboratory data. The sensitivity of procedure-based methods for identifying severe sepsis was 64.2%, and the specificity was 65.3%. Two diagnosis-based methods -the Angus and Martin algorithms- exhibited sensitivities of 21.7% and 14.6% and specificities of 98.7% and 99.5%, respectively, for severe sepsis. For DIC, the sensitivity of procedure-based methods was 55.6%, and the specificity was 67.1%, and the sensitivity and specificity of diagnosis-based methods were 35.8% and 98.2%, respectively., Conclusions: Procedure-based methods were more sensitive and less specific than diagnosis-based methods in identifying severe sepsis and DIC. Procedure records could improve disease identification in administrative databases.

Objectives: To compare mortality between de-escalation and continued empirical treatment in patients with community-acquired pneumonia., Methods: Using a nationwide administrative database, we identified adult patients with community-acquired pneumonia caused by Streptococcus pneumoniae, other streptococci, Haemophilus influenzae, Klebsiella pneumoniae, or Escherichia coli (n = 10,231) or of unknown etiology (n = 8247), discharged between July 2010 and March 2013. De-escalation was determined by the spectrum and number of antimicrobials at day 4. We used propensity score matching to obtain 489 pairs of de-escalation and continuation groups among pathogen-identified patients and 278 pairs among culture-negative patients to compare mortalities., Results: In the pathogen-identified patients, de-escalation was noninferior to continuation in 15-day mortality [5.3% in de-escalation versus 4.3% in continuation, a difference of 1.0% (95% confidence interval, -1.7% to 3.7%)] and in-hospital mortality [8.0% in de-escalation versus 8.8% in continuation, a difference of -0.8% (95% confidence interval, -4.3% to 2.7%)]. In the culture-negative cases, de-escalation was noninferior to continuation in terms of 15-day mortality but not in terms of in-hospital mortality., Conclusions: Among patients with community-acquired pneumonia of specific etiology, de-escalation was noninferior to continuation of empirical treatment, suggesting that de-escalation is a safe strategy and supporting current recommendations. Safety of de-escalation in culture-negative cases is questionable., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: Intravenous magnesium sulfate is used as adjunctive therapy for severe asthma exacerbations. However, previous randomized controlled trials of the administration of intravenous magnesium sulfate for asthma exacerbations have shown mixed results, and no study has evaluated its effect on mortality in patients with life-threatening asthma. The objective of this study was to investigate the association between intravenous magnesium sulfate administration and mortality in patients with severe asthma., Methods: Patients with severe asthma requiring intravenous corticosteroids and oxygenation were selected using the Japanese Diagnosis Procedure Combination inpatient database. One-to-one propensity score matching was performed between patients having received or not intravenous magnesium sulfate. Primary outcomes were 7-, 14- and 28-day mortalities. Secondary outcomes were total dose of intravenous corticosteroids during hospitalization, duration of mechanical ventilation and length of stay., Results: Among 14,122 eligible patients, 619 received intravenous magnesium sulfate. Propensity score matching created a matched cohort of 599 pairs with and without intravenous magnesium sulfate. There were no significant differences between patients with and without intravenous magnesium sulfate in terms of 28-day mortality (1.3% vs 1.8%, P = 0.488), median total dose of intravenous corticosteroids (2400 mg vs 2400 mg, P = 0.580), median duration of mechanical ventilation (1 day vs 1 day, P = 0.118) and median length of stay (16 days vs 13 days, P = 0.640)., Conclusion: This study found no significant benefit of intravenous magnesium sulfate use in terms of mortality in patients with severe acute asthma., (© 2016 Asian Pacific Society of Respirology.)

Background: Repeated drug overdose is a major risk factor for suicide. Data are lacking on the effect of psychiatric intervention on preventing repeated drug overdose., Aims: To investigate whether psychiatric intervention was associated with reduced readmission to emergency centres due to drug overdose., Method: Using a Japanese national in-patient database, we identified patients who were first admitted to emergency centres for drug overdose in 2010-2012. We used propensity score matching for patient and hospital factors to compare readmission rates between intervention (patients undergoing psychosocial assessment) and unexposed groups., Results: Of 29 564 eligible patients, 13 035 underwent psychiatric intervention. In the propensity-matched 7938 pairs, 1304 patients were readmitted because of drug overdose. Readmission rate was lower in the intervention than in the unexposed group (7.3% v . 9.1% respectively, P <0.001)., Conclusions: Psychiatric intervention was associated with reduced readmission in patients who had taken a drug overdose., Declaration of Interest: None., Copyright and Usage: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Objectives: Comorbidity measures are widely used in administrative databases to predict mortality. The Japanese Diagnosis Procedure Combination database is unique in that secondary diagnoses are recorded into subcategories, and procedures are precisely recorded. We investigated the influence of these features on the performance of mortality prediction models., Study Design and Setting: We obtained data of adult patients with main diagnosis of acute myocardial infarction, congestive heart failure, acute cerebrovascular disease, gastrointestinal hemorrhage, pneumonia, or septicemia during a 1-year period. Multiple models were constructed representing different subcategories from which Charlson and Elixhauser comorbidities were extracted. Prevalence of comorbidities and C statistics of logistic regression models predicting in-hospital mortality was compared. Associations between four procedures (computed tomography, oxygen administration, urinary catheter, and vasopressors) and mortality were also evaluated., Results: C statistics of the model using all secondary diagnoses (Charlson: 0.717; Elixhauser: 0.762) were greater than those using a limited subcategory to strictly specify comorbidities (Charlson: 0.708; Elixhauser: 0.744). However, misidentification of complications and main diagnoses as comorbidities was observed in the all-diagnosis model. The four procedures were associated with mortality., Conclusion: Subcategorized diagnoses allowed correct identification of comorbidities and procedures predicted mortality. Incorporation of these two features should be considered for other administrative databases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Risk adjustment is important in studies using administrative databases. Although utilization of diagnostic and therapeutic procedures can represent patient severity, the usability of procedure records in risk adjustment is not well-documented. Therefore, we aimed to develop and validate a severity index calculable from procedure records., Methods: Using the Japanese nationwide Diagnosis Procedure Combination database of acute-care hospitals, we identified patients discharged between 1 April 2012 and 31 March 2013 with an admission-precipitating diagnosis of acute myocardial infarction, congestive heart failure, acute cerebrovascular disease, gastrointestinal hemorrhage, pneumonia, or septicemia. Subjects were randomly assigned to the derivation cohort or the validation cohort. In the derivation cohort, we used multivariable logistic regression analysis to identify procedures performed on admission day which were significantly associated with in-hospital death, and a point corresponding to regression coefficient was assigned to each procedure. An index was then calculated in the validation cohort as sum of points for performed procedures, and performance of mortality-predicting model using the index and other patient characteristics was evaluated., Results: Of the 539 385 hospitalizations included, 270 054 and 269 331 were assigned to the derivation and validation cohorts, respectively. Nineteen significant procedures were identified from the derivation cohort with points ranging from -3 to 23, producing a severity index with possible range of -13 to 69. In the validation cohort, c-statistic of mortality-predicting model was 0.767 (95 % confidence interval: 0.764-0.770). The ω-statistic representing contribution of the index relative to other variables was 1.09 (95 % confidence interval: 1.03-1.17)., Conclusions: Procedure-based severity index predicted mortality well, suggesting that procedure records in administrative database are useful for risk adjustment.

Position-specific scoring matrix (PSSM) has been widely used for identifying protein functional sites. However, it is 20-dimentional and contains many redundant features. The Kidera factors were reported to contain information relating almost all physical properties of amino acids, but it requires appropriate weighting coefficients to express their properties. We developed a novel method, named as KSPSSMpred, which integrated PSSM and the Kidera Factors into a 10-dimensional matrix (KSPSSM) for ligand-binding site prediction. Flavin adenine dinucleotide (FAD) was chosen as a representative ligand for this study. When compared with five other feature-based methods on a benchmark dataset, KSPSSMpred performed the best. This study demonstrates that, KSPSSM is an effective feature extraction method which can enrich PSSM with information relating 188 physical properties of residues, and reduce 50% feature dimensions without losing information included in the PSSM.

Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been widely adopted by sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved at some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. Every value in PSSMs is calculated independently of each other, without carrying the contextual information of residues in the sequence. Therefore, adopting the direct output of PSSM for prediction fails to consider the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of combining PSSMs with the specific conservation patterns of functional sites for prediction, three different PSSM-based methods for identifying three kinds of functional sites have been analyzed. Results suggest that, different PSSM-based methods differ in their capability to identify different patterns of functional sites, and better combining PSSMs with the specific conservation patterns of residues would largely facilitate the prediction.

Background: Identifying ligand-binding sites is a key step to annotate the protein functions and to find applications in drug design. Now, many sequence-based methods adopted various predicted results from other classifiers, such as predicted secondary structure, predicted solvent accessibility and predicted disorder probabilities, to combine with position-specific scoring matrix (PSSM) as input for binding sites prediction. These predicted features not only easily result in high-dimensional feature space, but also greatly increased the complexity of algorithms. Moreover, the performances of these predictors are also largely influenced by the other classifiers., Results: In order to verify that conservation is the most powerful attribute in identifying ligand-binding sites, and to show the importance of revising PSSM to match the detailed conservation pattern of functional site in prediction, we have analyzed the Adenosine-5'-triphosphate (ATP) ligand as an example, and proposed a simple method for ATP-binding sites prediction, named as CLCLpred (Contextual Local evolutionary Conservation-based method for Ligand-binding prediction). Our method employed no predicted results from other classifiers as input; all used features were extracted from PSSM only. We tested our method on 2 separate data sets. Experimental results showed that, comparing with other 9 existing methods on the same data sets, our method achieved the best performance., Conclusions: This study demonstrates that: 1) exploiting the signal from the detailed conservation pattern of residues will largely facilitate the prediction of protein functional sites; and 2) the local evolutionary conservation enables accurate prediction of ATP-binding sites directly from protein sequence.

Background: Molecular recognition features (MoRFs) are short binding regions located in longer intrinsically disordered protein regions. Although these short regions lack a stable structure in the natural state, they readily undergo disorder-to-order transitions upon binding to their partner molecules. MoRFs play critical roles in the molecular interaction network of a cell, and are associated with many human genetic diseases. Therefore, identification of MoRFs is an important step in understanding functional aspects of these proteins and in finding applications in drug design., Results: Here, we propose a novel method for identifying MoRFs, named as MFSPSSMpred (Masked, Filtered and Smoothed Position-Specific Scoring Matrix-based Predictor). Firstly, a masking method is used to calculate the average local conservation scores of residues within a masking-window length in the position-specific scoring matrix (PSSM). Then, the scores below the average are filtered out. Finally, a smoothing method is used to incorporate the features of flanking regions for each residue to prepare the feature sets for prediction. Our method employs no predicted results from other classifiers as input, i.e., all features used in this method are extracted from the PSSM of sequence only. Experimental results show that, comparing with other methods tested on the same datasets, our method achieves the best performance: achieving 0.004~0.079 higher AUC than other methods when tested on TEST419, and achieving 0.045~0.212 higher AUC than other methods when tested on TEST2012. In addition, when tested on an independent membrane proteins-related dataset, MFSPSSMpred significantly outperformed the existing predictor MoRFpred., Conclusions: This study suggests that: 1) amino acid composition and physicochemical properties in the flanking regions of MoRFs are very different from those in the general non-MoRF regions; 2) MoRFs contain both highly conserved residues and highly variable residues and, on the whole, are highly locally conserved; and 3) combining contextual information with local conservation information of residues facilitates the prediction of MoRFs.

Background: Multiple sequence alignment (MSA) is a useful tool in bioinformatics. Although many MSA algorithms have been developed, there is still room for improvement in accuracy and speed. In the alignment of a family of protein sequences, global MSA algorithms perform better than local ones in many cases, while local ones perform better than global ones when some sequences have long insertions or deletions (indels) relative to others. Many recent leading MSA algorithms have incorporated pairwise alignment information obtained from a mixture of sources into their scoring system to improve accuracy of alignment containing long indels., Results: We propose a novel group-to-group sequence alignment algorithm that uses a piecewise linear gap cost. We developed a program called PRIME, which employs our proposed algorithm to optimize the well-defined sum-of-pairs score. PRIME stands for Profile-based Randomized Iteration MEthod. We evaluated PRIME and some recent MSA programs using BAliBASE version 3.0 and PREFAB version 4.0 benchmarks. The results of benchmark tests showed that PRIME can construct accurate alignments comparable to the most accurate programs currently available, including L-INS-i of MAFFT, ProbCons, and T-Coffee., Conclusion: PRIME enables users to construct accurate alignments without having to employ pairwise alignment information. PRIME is available at http://prime.cbrc.jp/.