Conservative management of spontaneous spinal epidural hematoma: A case report with favorable prognosis.

Sudden spinal epidural hematoma (SSEH) is relatively rare. Sudden pain from the neck to the back and subsequent extremity paralysis necessitate immediate head and cervical magnetic resonance imaging or computed tomography, keeping SSEH in mind. Although surgery is recommended for progressive paralysis, conservative treatment is indicated for mildly symptomatic cases.

Relationships between acute generalized eruptive pustulosis, age, sex, primary disease, and prescription medications: Further analysis of the Japanese Adverse Drug Event Report database.

Background: Acute generalized eruptive pustulosis (AGEP) is a rare, but serious, drug-related adverse event. This study aimed to determine the relationships between AGEP and age, sex, primary disease, and prescription medications using a database of adverse drug events, namely, the Japanese Adverse Drug Event Report (JADER) database. Methods: In this retrospective observational study, we analyzed AGEP reports extracted from the JADER database based on the preferred term for AGEP (code 10048799). We evaluated the effects of causative drugs, underlying diseases, age, and sex. The association between AGEP and prescription drugs was analyzed using the reporting odds ratio and adjusted for covariates using multiple logistic regression. Association rule mining was performed to evaluate the correlation between each combination of factors and AGEP. Results: Between April 2004 and March 2023, 823,662 reports, including 869 reports on AGEP, were entered in the JADER database. The highest percentage of reports in each age group was in males aged <10 years, and clarithromycin was the most used drug in males aged <10 years. Nasopharyngitis was the most common reason for use, and Kawasaki disease was reported as a reason for use among males under 10 years of age, but not among females. Conclusions: In boys aged <10 years, attention should be paid to the occurrence of AGEP when prescribing clarithromycin and treating Kawasaki disease.

Survey of community and hospital pharmacist involvement in outpatient chemotherapy using Japanese health information data.

In this study, information on injectable anticancer drug use and additional fee for enhanced collaboration (AEC) and additional fee for specific drug management guidance 2 (ASD2) claims from the NDB Open Data Japan (NODJ) dataset and the number of patients with cancer according to sex and age from the National Cancer Registry (NCR) dataset were integrated and evaluated to determine the current status and challenges in pharmacist interventions for patients receiving cancer treatment. The NODJ data, including receipt data billed from 2020 to 2021, were obtained from the Ministry of Health, Labour and Welfare website. The use of injectable anticancer drugs decreased relative to the number of cancer patients aged ≥ 75 years compared to those aged < 75 years. Regarding injectable anticancer drug use, the number of AEC claims was similar between men and women, but the number of ASD2 claims was lower in men than in women. The number of times community pharmacists claimed their ASD2 was approximately 5% of the number of times hospital pharmacists claimed their AEC. This study revealed that several patients did not receive sufficient guidance from community pharmacists compared to hospital pharmacists, suggesting a potential insufficiency in the collaboration between the two groups.

Analysis of drug-induced interstitial lung disease caused by herbal medicine using the Japanese Adverse Drug Event Report database.

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a severe adverse event leading to morbidity and mortality. This study evaluated the adverse event indicators of DIILD and time-to-onset profiles following the daily intake of herbal drugs (Scutellariae radix ["ogon" in Japanese], Bupleuri radix ["saiko" in Japanese], and Pinelliae tuber ["hange" in Japanese]) using the Japanese Adverse Drug Event Report database. DIILD was defined in accordance with the Medical Dictionary for Regulatory Activities. METHODS: The Japanese Adverse Drug Event Report database contained 830,079 reports published between April 2004 and April 2023. The association between herbal medicines and DILLD was evaluated using the pharmacovigilance index as the reporting odds ratio (ROR), logistic regression models, propensity score-matching techniques, and Weibull shape parameters. RESULTS: The adjusted RORs using multivariate logistic regression models for Scutellariae radix (daily intake), Pinelliae tuber (daily intake), sex (male), age (≥ 60 years), Scutellariae radix (daily intake)*age (≥ 60 years), and Scutellariae radix (daily intake)* Pinelliae tuber (daily intake) were 1.47 (1.36 - 1.59), 1.05 (1.01 - 1.10), 1.45 (1.34 - 1.57), 1.92 (1.74 - 2.11), 3.35 (3.12 - 3.60), and 1.49 (1.46 - 1.53), respectively. DIILD onset profiles were evaluated using the Weibull shape parameter. A logistic plot of daily intake and onset of DIILD was drawn. ROR signals were detected in 32 of 54 herbal medicines, including Scutellariae radix, Bupleuri radix, and Pinelliae tuber. The median duration (days) (interquartile range) to DIILD onset was 36.0 (27.0-63.0) for Saikokaryukotsuboreito, 35.0 (21.0-55.0) for Saireito, and 31.0 (13.5-67.5) for Shosaikoto. The Weibull shape parameter beta (95% confidence interval) values for Saikokaryukotsuboreito, Saireito, and Shosaikoto were 1.36 (1.08-1.67), 1.36 (1.20-1.52), and 1.31 (0.98-1.68), respectively. CONCLUSIONS: DIILD demonstrated a dose-dependent to crude drugs. Clinicians should strive for the early detection of DIILD and avoid the inadvertent administration of herbal medicines.

Progressive multifocal leukoencephalopathy analyzed using the Japanese Adverse Drug Event Report database.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) has been reported as the development of drugs with immunomodulatory properties, such as anticancer, immunosuppressive, and biological agents, has accelerated. To clarify an incidence profile of drug-associated PML in real-world clinical practice, we analyzed reported patients with PML using the Japanese Adverse Drug Event Report (JADER) database. METHODS: We analyzed PML reports extracted from the JADER database based on the preferred term of "progressive multifocal leukoencephalopathy" from between 2004 and 2021. This was a retrospective, observational study. We evaluated the effects of causative drugs, underlying diseases, and the age of the patients on the annual number of PML reports. RESULTS: The JADER database contained 773,966 reports published between April 2004 and March 2022, from which we identified 361 PML events. These PML events may include multiple counts of the same case reported by different pathways and patients diagnosed with probable or possible PML. The number of PML reports and reporting ratios have gradually increased over the past decade. The annual number of PML reports associated with biologics, immunosuppressants, and antineoplastic drugs showed an increasing trend. Females aged ≥30 years showed an increase in PML reports; in contrast, there the number of reports for males aged ≥50 years increased. CONCLUSIONS: The number of PML reports and reporting ratios have gradually increased in the past decade in Japan, and it considered that it was related to change in the treatment of malignancies and autoimmune diseases, and the increasing use of biologics, immunosuppressive agents, and antineoplastic agents.

Evaluation of neuroleptic malignant syndrome induced by antipsychotic drugs using spontaneous reporting system.

Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this study, the association between antipsychotic drugs and NMS was comprehensively evaluated by cluster and association analyses using the Japanese Adverse Drug Event Report (JADER) database. The analyses were performed using 20 typical antipsychotics (TAPs) alongside 9 atypical antipsychotics (AAPs). The Standardised MedDRA Queries (SMQ) database was used to analyze NMS (SMQ code: 20000044). Reporting odds ratios (RORs) were used for AE signal detection. The relationship between antipsychotic drugs and AEs for NMS was investigated by performing hierarchical cluster analysis using Ward's method. Between April 2004 and September 2021, the total number of JADER reports was 705,294. RORs (95 % confidence interval) of NMS for haloperidol, chlorpromazine, risperidone, and aripiprazole were 12.1 (11.1-13.3), 6.3 (5.7-7.0), 6.2 (5.8-6.6), and 4.7 (4.4-5.1), respectively. Three clusters were formed, with characteristics as follows: Cluster 1 consisted of only TAPs, such as bromperidol and fluphenazine, whilst having a high reporting rate of hypotension, tachycardia, dyskinesia, and dystonia. Cluster 2 consisted of all AAPs alongside several TAPs, such as haloperidol and chlorpromazine, with higher reporting rates of disturbance of consciousness, extrapyramidal disorders (excluding dyskinesia and dystonia), and serotonin syndrome. Cluster 3 consisted of only perphenazine, whilst having a higher reporting rate of coma, leukocytosis, and Parkinsonism. The results of this study may therefore aid in the management of NMS using antipsychotic drugs.

Profiles and Outcomes of Skin Injuries Caused by Injectable Drug Extravasation: An Analysis of the Japanese Adverse Drug Event Report Database.

Extravasation occurs when injectable drugs leak out of the blood vessels, damaging the surrounding tissues and causing a variety of skin injuries. This study aimed to comprehensively analyze extravasation risk, skin injury profiles, and outcomes for suspect drugs from the Japanese Adverse Drug Event Report (JADER) database. Adverse events were defined according to the Medical Dictionary for Regulatory Activities/Japanese version; the term extravasation (Standardized MedDRA Query Code: 20000136) was used in this analysis. The names of adverse events were entered as unified preferred terms and redefined to evaluate skin injury profiles. In addition, skin injury outcomes were divided into 2 broad categories: "improvement" and "no improvement." Reporting odds ratios were used to detect signals for adverse events. A total of 656 cases of extravasation-related adverse events were reported between April 2004 and January 2022. Signals for extravasation-related adverse events were detected from 11 drugs. Then, their respective skin injury profiles and outcomes were determined. These results suggest a relationship between adverse events associated with extravasation and 11 drugs and identify the characteristics of each skin injury and their outcomes. These findings will contribute to improving the quality of infusion management in clinical practice.

Systematic surveillance of immune-related adverse events in clinical practice and impact of subsequent steroid medication on survival outcomes.

BACKGROUND: Recent advances in immune-checkpoint inhibitors (ICIs) have highlighted the need for effective management of immune-related adverse events (irAEs). This study aimed to conduct a systematic surveillance of real-world development of irAEs for understanding their characteristics and examine the prognostic impact of steroid use for these events. METHODS: We retrospectively investigated cancer patients treated with ICIs between 2014 and 2021 and collected information about irAEs throughout their development, management, and clinical outcomes. RESULTS: Overall, 458 patients (45.4%) developed 670 irAEs. The prevalence of irAEs varied by cancer type, but it was increased in regimens with longer treatment durations. Severe irAEs were more common in the nivolumab + ipilimumab and pembrolizumab + axitinib regimens. Patients who received steroids for irAEs at a dosage of < 2 mg/kg had comparable prognosis to those who did not receive steroids; however, patients who received methylprednisolone pulse therapy, primarily for severe pneumonitis and hepatitis, had shorter overall survival than those who did not receive steroids (7.8 versus 23.4 months, p = 0.016). Furthermore, methylprednisolone pulse therapy for irAEs was a poor prognostic factor in multivariate analysis (hazard ratio: 2.19, 95% confidence interval: 1.34-2.86, p < 0.001). CONCLUSION: Steroid treatment for irAE does not affect prognosis and should thus be used promptly to control inflammation. However, pulse therapy for severe cases is a poor prognostic factor, and early detection remains the key to managing such irAEs. The irAE characteristics in each regimen should be clarified to establish and provide more sophisticated irAE management, and the current findings will be beneficial to this goal.

Promoting generic drug usage in Japan: correlation between generic drug usage and monthly personal income.

BACKGROUND: To reduce pharmacy-related medical expenses, it is necessary to cut drug costs, potentially by increasing generic drug usage. This study analyzes the correlation between generic drug usage and monthly personal income by examining prescriptions for individual drugs. METHODS: We conducted a cross-sectional study based on the data set from the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan and the Basic Survey on Wage Structure. We calculated the correlation coefficient between the usage rate of generic drugs in each prefecture of Japan and monthly personal incomes. We then analyzed the correlation coefficients based on the therapeutic categories of medicinal drugs; the contingency table was visualized as a mosaic plot. To compare the proportions between multiple categories, the chi-squared test was applied as a statistical significance test that was used in the analysis of n × m contingency tables. We worked with the null hypothesis that there were no differences between classes in the population. RESULTS: Regarding the correlation coefficient between the usage rate of generic drugs and monthly personal incomes, the proportion of negative correlation coefficients for outpatient out-of-hospital and outpatient in-hospital prescriptions was over 70%, while that for inpatient prescriptions was 46.9%. The proportion of medicinal drugs exhibiting a negative correlation between the rates of generic drug usage and monthly personal incomes for outpatient out-of-hospital prescriptions and outpatient in-hospital prescriptions was higher than that of inpatient prescriptions. The proportion of statistically correlated medicinal drugs among inpatient prescriptions was lower than that among outpatient out-of-hospital and outpatient in-hospital prescriptions. The proportions of significant negative correlations for outpatient out-of-hospital, outpatient in-hospital, and inpatient prescriptions were 30.6%, 22.7%, and 3.5%, respectively. It was also observed that the rate of generic prescription usage for outpatient out-of-hospital and in-hospital prescriptions increased as monthly personal incomes decreased. In outpatients, the therapeutic categories with strong negative correlations were vasodilators and hyperlipidemia drugs. CONCLUSIONS: Our results may help to increase the usage rate of generic drugs in different prefectures by providing useful information for promoting them throughout Japan.

Predictive value of serum high-mobility group box 1 levels for checkpoint inhibitor pneumonitis.

BACKGROUND AND OBJECTIVE: Checkpoint inhibitor pneumonitis (CIP), caused by the anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) antibody, can be a fatal adverse event in cancer patients. However, no predictive biomarkers for CIP have been identified. Because high-mobility group box 1 (HMGB1) can aggravate lung injury and potentially increase the immune response, it was investigated as a predictive blood marker. METHODS: Blood samples, prospectively stored before anti-PD-1/PD-L1 monotherapy between December 2015 and October 2020, were obtained at two university hospitals from 87 and 43 non-small cell lung cancer (NSCLC) patients (discovery and validation cohorts, respectively). We retrospectively evaluated the association of serum HMGB1 levels with the incidence of CIP developed within 3 months of initiating anti-PD-1/PD-L1 therapy. RESULTS: CIP was observed in 9 (10.3%) and 6 (14.0%) patients in the discovery and validation cohorts, respectively. In each cohort, serum HMGB1 levels were significantly and reproducibly higher in patients with CIP. In the discovery cohort, an HMGB1 cut-off level of 11.24 ng/ml was identified by receiver operating characteristic analysis. CIP incidence in the HMGB1high subgroup was significantly higher than that in the HMGB1low subgroup in the discovery (41.2% vs. 2.9%) and validation cohorts (36.4% vs. 6.3%). In an exploratory pooled analysis, three patients died of grade 5 CIP; a 19.29 ng/ml HMGB1 cut-off level detected grade 5 CIP with 100% sensitivity and 96.85% specificity. CONCLUSION: Our results suggest that HMGB1 may be a potential blood marker to predict the development and severity of CIP in NSCLC patients.

Association Between Patient Preference for Inhaler Medications and Asthma Outcomes.

Purpose: Asthma guidelines recommend considering the patient preference to optimize medication choices. Patient preference for inhaler medication may affect asthma outcomes, but evidence regarding this is lacking. This study investigated the associations between patient preference for inhaler medications and asthma outcomes. Patients and Methods: A multicenter questionnaire survey was conducted among 351 adult patients with asthma treated with regular inhaled corticosteroids. Agreement between patients' preferences and current medication was evaluated using two questions: matched preference was defined as patients answering that the current inhaler medication was the most preferred treatment and they were satisfied with it. Mismatched preference was defined as when patients reported that the current inhaler medication was not the most preferred treatment and/or they were not satisfied with it. We investigated the factors associated with patient preference for asthma inhaler medications. Results: In total, 269 (76.6%) patients were classified into the matched preference group and 82 (23.4%) patients into the mismatched preference group. Multivariate analyses showed that matched preference was independently associated with higher asthma control test scores (P<0.001), fewer exacerbations (P=0.009), less regular oral corticosteroid use (P=0.009), and better inhaler adherence (P=0.006) than the mismatched preference group. In subgroup analysis, younger age was associated with matched preference in patients using dry powder inhalers but not in those using pressurized metered dose inhalers. Conclusion: The use of preference-matched inhaler medication was associated with better asthma outcomes. Evaluation of patients' preference for inhaler medication might provide useful information for individualized treatment with asthma inhaler medications.

Restrictive and stimulative impacts of COVID-19 policies on activity trends: A case study of Kyoto.

This paper employs regression with ARIMA errors (RegARIMA) to quantify the impacts of multiple non-pharmaceutical interventions, daily new cases, seasonal and calendar effects, and other factors on activity trends across the timeline of the ongoing COVID-19 pandemic in Japan. The discussion focuses on two controversial policy sets imposed by the Japanese government that aim to contain the pandemic and to stimulate the recovery of the economy. The containing effect was achieved by stay-at-home requests and declaring a "State of Emergency" in the combat against the first waves of infectious cases. After observing reduced cases, Go-to-travel and Go-to-eat campaigns were launched in July 2020 to encourage recreational travel and to revive the economy. To better understand the impact of the policies we utilize "Google trends" which measure how much these policies are looked up online. We suggest this reflects how much they are part of the public discussion. A case study is conducted in Kyoto, a city famous for tourism. The proposed RegARIMA model is compared with linear regression and time series models. The outperformances in measuring the magnitude of intervention impacts and forecasting the future trends are confirmed by using a total of twelve activity and mobility indices as the dependent variable. Nine indices are released by Google and Apple and three are obtained from local Wi-Fi packet sensors. The effect of the State of Emergency declaration is found to erode at the second implementation, and the second stage of the Go-to-travel campaign successfully stimulated travel demand in the autumn sighting season of 2020.

Early Detection of Cardiac Amyloidosis in Transthyretin Mutation Carriers.

Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

Role of Soluble Receptor for Advanced Glycation End Products in Postoperative Fibrotic Lung Injury.

BACKGROUND: In lung cancer patients with interstitial lung disease (ILD) postoperative acute exacerbation can be fatal. However the predictive biomarkers for postoperative exacerbation of ILD have not been fully elucidated. The soluble receptor for advanced glycation end products is a lung-derived antiinflammatory protein that can prevent acute lung injury. This study aimed to elucidate its role in this fatal complication, especially focusing on the predictive potential of serum levels of soluble receptor for advanced glycation end products. METHODS: We retrospectively enrolled 152 patients with lung cancer and ILD who underwent lung resection and had blood samples collected before surgery. Independent predictors of postoperative acute exacerbation were evaluated in all patients and in subgroups based on the surgical procedure. Additionally serial changes in soluble receptor levels in these subgroups were evaluated. RESULTS: Seventeen patients (11.2%) developed postoperative acute exacerbation. Receiver operating characteristic curve analysis revealed 547.4 pg/mL as the optimal soluble receptor level cutoff value. Univariate and multivariate logistic regression analyses revealed a significant association between soluble receptor serum levels (≤547.4 pg/mL) and postoperative acute exacerbation. In the subgroup analysis this independent association was observed only in the lobectomy group. Additionally lobectomy caused a significant reduction in postoperative soluble receptor levels. CONCLUSIONS: Decreased baseline levels of circulatory soluble receptor might be a potential risk factor for postoperative acute exacerbation in patients with lung cancer and ILD. Moreover additional reduction in the levels of this antiinflammatory protein occurs because of lung resection.

Development of Liquid-Chromatography Tandem-Mass-Spectrometry Method for Determining Environmental Contamination by Powdered Medicinal Drugs in Pharmacies.

The environment and personnel are both exposed to powdered pharmaceuticals inside pharmacies. This makes developing new methods for rapidly determining such contaminants an important objective. In this study, we developed a liquid-chromatography tandem-mass-spectrometry (LC-MS/MS) method for the simultaneous qualitative and quantitative determination of powdered medicinal drugs, such as famotidine, risperidone, lansoprazole, olanzapine, haloperidol, clarithromycin, promethazine, levomepromazine, and chlorpromazine. The method involves the use of acetaminophen as the internal standard, an LC-MS/MS method with a core-shell column, and a 10 mM ammonium formate/acetonitrile gradient mobile phase. The analytes were separated within 14 min, and MS with an electrospray ionization source in positive-ion mode was used. The limits of detection for the 9 drugs were .1-8.4 ng/mL. Linear calibration curves in the 10-50 000 ng/mL range were constructed, and inter-day accuracies of 92.6-113.8% were determined for the 9 drugs. The coefficients of variation were less than 14.6%. These data suggest that the proposed method is applicable for the routine assaying of powdered-medicine contamination in pharmacies.

Pseudohypoxic brain swelling and secondary hydrocephalus with pseudomeningocele after lumbar surgery: a case report.

BACKGROUND: Postoperative intracranial complications are rare in spine surgery not including cranial procedures. We describe an uncommon case of pseudohypoxic brain swelling (PHBS) and secondary hydrocephalus after transforaminal lumbar interbody fusion (TLIF) presenting as impaired consciousness and repeated seizures. CASE PRESENTATION: A 65-year-old man underwent L4-5 TLIF for lumbar spondylolisthesis and began experiencing generalized seizures immediately postoperatively. Computed tomography (CT) revealed diffuse cerebral edema-like hypoxic ischemic encephalopathy. He was transported to our hospital, at which time epidural drainage was halted and anti-edema therapy was commenced. His impaired consciousness improved. However, he suffered secondary hydrocephalus due to continuous bleeding from a dural defect and spinal epidural fluid collection 3 months later. Following the completion of dural repair and insertion of a ventriculoperitoneal shunt, his neurologic symptoms and neuroimaging findings improved significantly. CONCLUSIONS: PHBS can be considered in patients with unexpected neurological deterioration following lumbar spine surgery even with the absence of documented durotomy. This might be due to postoperative intracranial hypotension-associated venous congestion, and to be distinguished from the more common postoperative cerebral ischemic events-caused by arterial or venous occlusions-or anesthetics complications.

Association between glucose intolerance and chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease.

PURPOSE: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. METHODS: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. RESULTS: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057-9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023-0.290) and 0.474 (0.213-1.109) µg/mL, P = 0.001]. CONCLUSION: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia.

Pharmacovigilance study of anti-infective-related acute kidney injury using the Japanese adverse drug event report database.

BACKGROUND: Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKI, along with patients' age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infective-related AKI-onset profiles. METHOD: We calculated reporting odds ratios (RORs) for reports of anti-infective-related AKI (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated the effect of anti-infective combination therapy. The background factors of cases with anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were matched using propensity score. We evaluated time-to-onset data and hazard types using the Weibull parameter. RESULTS: Among 534,688 reports (submission period: April 2004-June 2018), there were 21,727 AKI events. The reported number of AKI associated with glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were 596, 494, 341, 315, and 313, respectively. Crude RORs of anti-infective-related AKI increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 1.94 (1.80-2.09)] than in monotherapies [ROR, 1.29 (1.22-1.36)]. After propensity score matching, the adjusted RORs of anti-infective monotherapy and combination therapy (≥ 2 anti-infectives) were 0.67 (0.58-0.77) and 1.49 (1.29-1.71), respectively. Moreover, 48.1% of AKI occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation. CONCLUSION: RORs derived from our new SRS analysis indicate potential AKI risks and number of administered anti-infectives.

Circulation of fibrous microplastic (microfiber) in sewage and sewage sludge treatment processes.

The fate of microplastics (MPs) in the sewage treatment process has been investigated worldwide, and novel results have been reported; few studies have also clarified the fate of MPs in the sewage sludge treatment process. Although most MPs in sewage are transferred to sludge, some flow back from the sludge treatment process to the sewage treatment process. Therefore, throughout the sewage treatment plant, the removal rate of MPs may increase via a countermeasure during the sludge treatment process. In this study, samples obtained from sewage and sewage sludge treatments were used to degrade organic matter with hydrogen peroxide. Water sample particles were trapped on Ni filters with 20-µm-sized pores, dried at room temperature and then the MPs were detected and identified by FTIR microscopy. Note that sludge samples were treated with hydrogen peroxide and separated by specific gravity using NaI solution. The concentration of MPs per unit volume was then calculated and the MPs load was estimated using flow rates of water and sludge. Subsequently, we clarified the fate of MPs with sizes of 20 µm or greater in a sewage treatment plant. When the MPs load in the influent sewage is 100%, 12% of the MPs were found to return to the sewage treatment process via the sidestream of the sludge treatment process. Per this observation, it was made evident that MPs are in fact circulating throughout the sewage and sludge treatment processes. MPs in the sidestream mainly consisted of the effluent from the sludge concentration process, and most MPs were thought to be fibrous polyethylene terephthalate (fibrous MPs, i.e. microfibers [MFs]). The results show that MFs circulate throughout the sewage and sludge treatment processes, and for effectively increasing the removal rate of MPs, the removal of MFs proves correspondingly effective during the sludge treatment process.

Predictive role of circulatory HMGB1 in postoperative acute exacerbation of interstitial lung disease in lung cancer patients.

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29-11.70] ng/mL vs. 3.55 [2.07-5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.