Japanese Database Research Articles

Favorable Impact of Azithromycin on Patients in the Intensive Care Unit with Coronavirus Disease 2019: Insights from the First Wave Using a Japanese Database

BackgroundAzithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory properties. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently administered before specific treatments were developed. However, the efficacy of this treatment has not been verified. We retrospectively investigated the effects of its intravenous (IV) administration in patients with severe/critical COVID-19 using the National Administrative Database of Japan during the first wave (February–April 2020). MethodsPatients were categorized based on whether they received IV azithromycin within three days of hospitalization. An overlap weighting method with estimated propensity scores was used to reduce bias. ResultsAmong the 830 patients with severe/critical COVID-19, 148 (17.8%) received azithromycin, and 682 (82.2%) did not. After adjustment, the use of azithromycin was associated with a shorter duration of intensive care unit (ICU) management (-3.48 days, 95% confidence interval [CI]: -4.59 to -2.38). However, other endpoints, including mortality rate, duration of mechanical ventilation, and duration of hospital stay, did not suggest any associations. Furthermore, of the 115 ICU patients, 27 (23.5%) were treated with IV azithromycin and 88 (76.5%) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95% CI: 0.22 to 0.92), 30-day mortality (OR, 0.46, 95% CI: 0.22 to 0.94), and a shorter duration of ICU management (-2.94 days, 95% CI: -5.15 to -0.73). ConclusionWe verified that IV azithromycin was associated with favorable impact in patients with COVID-19 requiring ICU management.

Impact of inpatient cardiac rehabilitation on hospital-associated disability for older patients undergoing transcatheter aortic valve implantation: insight from the JROAD/JROAD-DPC database

Abstract Background Hospital-associated disability (HAD), a decline in the ability to perform activities of daily living (ADL) during hospitalization, is a modifiable target in the integrated care for older adults. Inpatient rehabilitation during the perioperative period is a part of a comprehensive cardiac rehabilitation (CR) program and plays a pivotal role in functional recovery and smooth reintegration into the home, community, and workplace after surgery. Prior research, including meta-analyses, have shown that outpatient CR participation after discharge of patients who underwent transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement is associated with a significant improvement in exercise capacity and indexes of ADL. However, the impact of inpatient CR on the occurrence of HAD remains unexplored. Purpose Using a large real-world nationwide database in Japan, the aim of this study was to determine the prevalence of HAD and the impact of inpatient CR participation on the development of HAD in older patients undergoing TAVI. Methods Older patients undergoing TAVI were extracted from the Japanese nationwide database (JROAD-DPC) from April 2014 to March 2021 and were divided into patients receiving inpatient CR (CR group) and non-CR group. HAD was defined as a decrease in the Barthel Index score ≥ 5 points at discharge relative to admission. Results Of 19,789 eligible patients, 17,066 (86%) underwent inpatient CR (average age, 84.3 ± 4.9 years; Woman, 65%). The overall prevalence of HAD was 9.6%, with a lower incidence in the CR group than those in the non-CR group (8.8% vs. 14.2%, p < 0.01). Participation in inpatient CR was associated with a significantly lower odds ratio (OR) of HAD in multivariate logistic regression analysis (adjusted OR, 0.62; 95% confidence interval [CI], 0.54–0.70; p < 0.01) and in inverse probability of treatment weighting-adjusted logistic regression analyses (adjusted OR, 0.82; 95% CI, 0.77–0.88; p < 0.01; Table). Analyses in subgroups of interest showed heterogeneity of the effects of inpatient CR with possible loss in patients with a body mass index of less than 18.5 kg/m² or BI score of less than 60 points at admission (Figure). Conclusions A substantial number of older patients undergoing TAVI developed HAD during perioperative period. Participation in inpatient CR was associated with a lower likelihood of HAD in TAVI recipients, but the benefit of inpatient CR for development of HAD was possibly lost in patients with a low BMI and low a BI score at admission, indicating the necessity of HAD-targeted multidisciplinary CR for lean patients with ADL disability before TAVI.Figure

The impact of daily step count with mobile health apps on clinical outcomes among general population

Abstract Background/Introduction Numerous studies have investigated the correlation between daily step count and the reduction of all-cause mortality and cardiovascular events. However, the optimal daily step count for the general population remains controversial. Purpose This study aims to assess cardiovascular risk based on individual step counts using a large cohort that includes step count data from mHealth Apps (Kencom), health checkups databases, and Japanese insurance claims databases. Methods We analyzed data from 85,204 users registered with Kencom between January 2016 and September 2021. The mean step count during one year before and after baseline data collection was used to define each individual's step count. We divided participants into low (N=45,539) and high (N=39,665) step count groups based on their mean step counts. Additionally, we categorized users into five groups based on their step counts (<4000; 4000-5999; 6000-7999; 8000-9999; and ≥10000) to evaluate cardiovascular events. The primary outcome was the occurrence of cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation, as classified by the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The cumulative incidence was estimated over 5 years. Results The high step count group was generally younger and predominantly male. No significant differences in cardiovascular risk factors such as hypertension, dyslipidemia, diabetes mellitus, and current smoking status were found between the two groups. Stratifying baseline characteristics by step count revealed significant differences among the five groups, with the exception of sex. The cumulative incidence of cardiovascular events was significantly lower in the high step count group compared to the low step count group (6.5% vs. 7.5%, log-rank P=0.005, Figure 1). After adjusting for confounding factors, the risk reduction of the high step count group remained significant (HR: 0.92, 95% CI: 0.87-0.98, P=0.005). Among the five step count groups, the incidence of primary outcome significantly differed, with only Group 5 (≥10000 steps) showing a significant reduction in the risk of cardiovascular events compared to Group 1 (<4000 steps) after adjustment (HR: 0.87, 95% CI: 0.77-0.99, P=0.03). Subgroup analyses based on sex indicated that the risk reduction was significant in males in Group 5 but not in females. Conclusion The risk of cardiovascular events was higher in the low step count group compared to the high step count group. After adjusting for confounders, only the highest step count group (≥10,000 steps/day) showed a significant reduction in cardiovascular event risk compared to the lowest step count group.

Volume-outcome relationships for intra-aortic balloon pump in acute myocardial infarction

Abstract Background Acute myocardial infarction (MI) is one of the major scenarios of intra-aortic balloon pump (IABP) use, particularly when complicated by cardiogenic shock. The utilization of mechanical circulatory support devices including IABP varies widely per hospital, while whether a higher IABP volume at each hospital is translated into better outcomes in acute MI is unclear. Purpose To evaluate the relationship between the volume of IABP use and mortality at the hospital level in patients with acute MI undergoing percutaneous coronary intervention (PCI). Methods Using a Japanese nationwide administrative database, a total of 26,490 patients with acute MI undergoing primary PCI from 154 hospitals were included. The primary endpoint was the observed/predicted in-hospital mortality ratio. The predicted mortality per patient was calculated using baseline variables and was averaged for each hospital. The associations among PCI volume for acute MI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed at the hospital level. Results Of the 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of IABP use per hospital in acute MI was 4.5 [2.4-10.7]. In lower primary PCI volume centers, IABP was more likely to be underused than expected, and the observed/predicted in-hospital mortality ratio was higher than in higher volume centers (Figure). The observed/predicted mortality ratio seemed lowest in hospitals where the observed/predicted IABP use ratio was around one. Conclusions The present study showed that the lower annual number of IABP use was associated with an increased mortality risk at the hospital level, and suggested that standardized IABP use can be an institutional quality indicator in a setting of acute MI.

Guideline-directed medical therapy implementation changes after acute coronary syndrome and their effect of prognosis: insights from Japanese real-world database using a storage system

Abstract Background The implementation of guideline-directed medical therapy (GDMT) after acute coronary syndrome (ACS) was reported to improve prognosis. However, there have been limited number of real-world studies clarifying the association between the status of GDMT implementation and clinical prognosis in ACS patients based on recent multicenter database. Purpose The purpose of this study was to survey the extent to which GDMT was performed over time in patients after percutaneous coronary intervention (PCI) for ACS, as well as to investigate the prognostic impact of GDMT. Methods This study is a retrospective, multicenter, observational study. We developed the Clinical Deep Data Accumulation System (CLIDAS), which consists of 6 university hospitals and the national cardiovascular center in Japan, directly obtains clinical data including patients background, laboratory data, echocardiogram, electrocardiogram, cardiac catheterization report, prescription, and long-term outcome from electronic medical records. 4107 patients who underwent PCI for ACS and were prescribed one or more antiplatelet drugs at baseline from April 2013 to March 2019 were analyzed, and divided into GDMT group (n = 2514) and non-GDMT group (n = 1593). GDMT was defined as all prescriptions for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, beta-blocker, and statin at baseline. The primary outcome was the major adverse cerebrocardiovascular event (MACCE) defined as being the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Results The median follow-up duration was 2.36 years (interquartile range: 0.78-4.00 years). The study cohort consisted of 76% of men with a median age of 71 years. The incidence of MACCE was significantly lower in the GDMT group than in the non-GDMT group (8.8% vs. 13.0%, log rank P <0.001). Multivariable Cox regression analyses revealed that the GDMT group was a lower hazard ratio (HR) for MACCE after adjusting for confounding factors including the information about the first half and the second half (HR, 0.80; 95% confidence interval, 0.65-0.98; P = 0.035). The implementation rate of GDMT in the first half group (from April 2013 to March 2016) was lower than that in the second half group (from April 2016 to March 2019) (58.3% vs. 64.4%, P <0.001). Conclusion The real-world CLIDAS database revealed that GDMT was significantly associated with the reduction of MACCE in patients with ACS after PCI. In addition, an increase in the rate of GDMT implementation over time was observed.Kaplan-Meier curves for MACCE

Factors associated with neurological outcomes in patients experiencing out-of-hospital cardiac arrest and severe acidaemia: retrospective analysis of a nation-wide registry

Background and objectiveAcidaemia is common among individuals who experience out-of-hospital cardiac arrest (OHCA). While severe acidaemia is a strong predictor of unfavourable outcomes, a subset of patients exhibits dramatic recovery. Despite these conflicting outcomes, little is known about the factors associated with neurological outcomes in those who experience OHCA with severe acidaemia. MethodsThis retrospective analysis used data from a Japanese multicentre nationwide database, the Japanese Association for Acute Medicine OHCA Registry. The analysis included data from adult patients with OHCA for whom blood pH data were available upon arrival to hospital. The primary outcome was 30-day survival with favourable neurological outcomes, defined as a Glasgow-Pittsburgh cerebral performance category score of 1 or 2. Patients were categorised with severe acidaemia if their blood pH was ≤ 6.8. Factors associated with favourable outcomes were investigated using multiple logistic regression analysis. ResultsData from 49,044 patients were included in the analysis, of whom 16,620 exhibited severe acidaemia with a median pH of 6.70 (interquartile range [IQR] 6.61–6.76], and 0.5% (86/16,620) experienced a neurologically favourable outcome. After adjustment for important prognostic factors, witnessed status exhibited a strong association with favourable neurological outcome (adjusted odds ratio [aOR] 6.46 [95% confidence interval (CI) 2.64–15.8]), while initial blood pH exhibited no significant association (aOR 0.90 with every 0.1 unit increase [95% CI 0.71–1.14]). ConclusionAlthough the number is small, a notable number of patients with severe acidaemia exhibited good neurological recovery. Witness status was critical for the prognosis of these patients.

Adding Biomarker Change Information to the Kidney Failure Risk Equation Improves Predictive Ability for Dialysis Dependency in eGFR <30 mL/min/1.73m2

Abstract Background Although the Kidney Failure Risk Equation (KFRE), a well-known predictive model for predicting dialysis dependency, is useful, it remains unclear whether the addition of biomarker changes to the KFRE model in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 will improve its predictive value. Methods We retrospectively identified adults with eGFR < 30 mL/min/1.73 m2 without dialysis dependency, and available health checkup data for 2 successive years using a large Japanese claims database (DeSC, Tokyo, Japan). We dichotomized the entire population into 50% training set and the other half as validation set. To assess the incremental value in the predictive ability for dialysis dependency by the addition of changes in eGFR and proteinuria, we calculated the difference in the C-statistics and net reclassification index (NRI). Results We identified 4,499 individuals and observed 422 individuals (incidence of 45.2 per 1000 person-years) who developed dialysis dependency during the observation period (9,343 person-years). Adding biomarker changes to the KFRE model improved C-statistics from 0.862 to 0.921, with an improvement of 0.060 (95% CI of 0.043–0.076, P <0.001). The corresponding NRI was 0.773 (95% CI: 0.637– 0.908), with an NRI for events of 0.544 (95% CI of 0.415–0.672) and NRI for non-events of 0.229 (95% CI of 0.186–0.272). Conclusions The KFRE model was improved by incorporating yearly changes in its components. The added information may help clinicians identify high-risk individuals and improve their care.

Diagnostic validity and solute-corrected prevalence for hyponatremia and hypernatremia among 1,813,356 admissions

Abstract Background and hypothesis We aimed to evaluate the diagnostic validity of the International Classification of Diseases, 10th Revision (ICD-10) codes for hyponatremia and hypernatremia, using a database containing laboratory data. We also aimed to clarify whether corrections for blood glucose, triglyceride, and total protein may affect the prevalence and the diagnostic validity. Methods We retrospectively identified admissions with laboratory values using a Japanese hospital-based database. We calculated the sensitivity, specificity, and positive/negative predictive values of recorded ICD-10-based diagnoses of hyponatremia (E87.1) and hypernatremia (E87.2), using serum sodium measurements during hospitalization (<135 mmol/L and >145 mmol/L, respectively) as the reference standard. We also performed analyses with corrections of sodium concentrations for blood glucose, triglyceride, and total protein. Results We identified 1,813,356 hospitalizations, including 419,470 hyponatremic and 132,563 hypernatremic cases based on laboratory measurements and 18,378 hyponatremic and 2,950 hypernatremic cases based on ICD-10 codes. The sensitivity, specificity, positive predictive value, and negative predictive value of the ICD-10 codes were 4.1%, 99.9%, 92.5%, and 77.6%, respectively, for hyponatremia and 2.2%, >99.9%, 96.5%, and 92.8%, respectively, for hypernatremia. Corrections for blood glucose, triglyceride, and total protein did not largely alter diagnostic values, though prevalence changed especially after corrections for blood glucose and total protein. Conclusions The ICD-10 diagnostic codes showed low sensitivity, high specificity, and high positive predictive value for identifying hyponatremia and hypernatremia. Corrections for glucose or total protein did not affect diagnostic values but would be necessary for accurate prevalence calculation.

A Study of the Factors Impeding Proper Dietary Habits: An Investigation Using the Japanese Comprehensive Survey of Living Conditions

(1) Background: Diet is significant for nutritional intake and serves as an essential element for improving quality of life (QOL). Poor dietary management skills increase the risk of onset or progression of lifestyle-related diseases, and, in particular, are a factor in reduced QOL during old age. This study aimed to clarify the physical and social background factors impeding dietary self-management. (2) Methods: The study participants were 3814 men (age range, 30–69 years) extracted from anonymous data comprising 15,294 persons provided from the Japanese national statistics database. The participants were classified into two groups (Concerned vs. Unconcerned) according to whether they were concerned about their diet. Adjusted odds ratios (ORs) for diet-conscious behaviors were then obtained by means of binomial logistic regression analysis performed following univariate analysis. (3) Results: The Concerned and Unconcerned groups comprised 2548 (66.8%) and 1266 subjects (33.2%), respectively. The diet-conscious behavior with the highest response rate was eating regularly (46.7%). The most frequent items in the Unconcerned group were the subjective symptom “irritable” (48.9%), high stress (46.3%), working more than 56 h/week (43.8%), and smoking (41.9%). The only item with a large significant OR in the binomial logistic regression analysis was smoking (OR: 2.2). (4) Conclusions: These results suggest that a smoking habit and stress are factors that impede diet management behaviors.

Evaluation of β-Blocker-Induced Bradyarrhythmia Using an Analysis of the Japanese Adverse Drug Event Report Database.

β-Adrenergic receptor blockers (β-blockers) are used to treat hypertension, ischemic heart disease, chronic heart failure, and tachyarrhythmia. The main side effects of treatment include bradycardia, atrioventricular block, and hypotension. Bradycardia may result in pacemaker implantation as well as the discontinuation of β-blockers. Bradycardia is difficult to confirm at a single institution because it diagnosed only by symptoms when electrocardiogram (ECG) are not routinely performed. Previous studies reported an increase in bradycardia in heart failure patients treated with β-blockers; however, limited information is currently available for non-heart failure patients. Bradycardia induced by β-blockers has not yet been comprehensively examined. Therefore, the present study investigated data on the incidence and duration of bradyarrhythmia caused by β-blockers using the Japanese Adverse Drug Event Report database (JADER). Cases of adverse effects associated with this medication were extracted from JADER and Fisher's exact test was performed to assess whether each β-blocker caused bradyarrhythmia. In addition, only data from patients who reported bradyarrhythmia after β-blocker treatment were extracted, and the Weibull distribution was used to analyze the time-to-onset of bradyarrhythmia. Thirteen β-blockers caused bradyarrhythmia and signals were observed for 12 drugs, except nadolol. Bradyarrhythmia induced by oral β-blockers was more likely to be of the early failure type, and developed within 2 months of treatment initiation with most β-blockers. A comprehensive analysis of bradyarrhythmia with β-blockers suggests that careful monitoring is needed, particularly early in the initiation of treatment.

Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database—authors’ response

Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database—authors’ response

Policy Decision-Making for Population Decline Using AI to Estimate Population Density From Well-Being Indicators

This paper examines whether a model that infers habitable area population density from regional well-being indicators can serve as a guide for policy decision-making to address population decline. The study uses 51 subjective evaluation items from the regional well-being indicators and habitable area population density calculated from e-stat, a Japanese government database. The inference model was created through ensemble learning, generating six weak learners and combining them with a meta-model to form the final model. Using data from Shimonoseki City in Yamaguchi Prefecture, Japan, we varied the value of a single subjective evaluation item to observe changes in the inferred population density. The results showed that subjective evaluations related to public transportation, crime prevention, dining options, and local government initiatives significantly impact habitable area population density. Prioritizing these factors could enhance resident satisfaction and potentially mitigate the issue of population decline.

Disproportionality analysis of flutamide- or bicalutamide-induced liver injury with and without steroids by using the Japanese Adverse Drug Event Report database.

Although the mechanism underlying flutamide- or bicalutamide-induced liver injury may be immune related, the details remain unclear. If this mechanism is immune related, steroid use may be considered as a treatment option. Disproportionality analysis was conducted to evaluate the effect of concomitant steroid use on flutamide- and bicalutamide-induced liver injury. Male patients aged 20years or older who were receiving nonsteroidal anti-androgens from April 2004 to October 2023 were screened from the Japanese Adverse Drug Event Report database. Data on liver injury, age, weight, height, steroid use, obesity, hepatic stenosis, alcohol-related hepatic disorders, hepatitis B and C, and common drugs known to cause drug-induced liver injury were analyzed. Liver injury was defined by the Standardized Medical Dictionary for Regulatory Activities query index (code 20000006, version 27.0). Among 142,430 patients, 2,316 were administered nonsteroidal anti-androgens. Reports of liver injury were disproportionate depending on the agents used (reporting odds ratio [ROR], 1.29; 95% confidence intervals [CI], 1.13-1.46), especially among flutamide or bicalutamide users (flutamide: ROR, 6.09; 95% CI, 4.51-8.23; bicalutamide: ROR, 1.24; 95% CI, 1.05-1.48). Multivariable logistic regression analysis correlated steroid use with a lower risk of flutamide- or bicalutamide-induced liver injury (flutamide: odds ratio, 0.07; 95% CI, 0.01-0.52; bicalutamide: odds ratio, 0.45; 95% CI, 0.21-0.96). Our findings suggest that flutamide and bicalutamide may increase the risk of liver injury compared to enzalutamide, apalutamide, and darolutamide. Furthermore, our study indicated that steroid use could aid in the management of liver injury.

Uncertainties of Economic Policy and Government Management Stability Played Important Roles in Increasing Suicides in Japan from 2009 to 2023.

Standardized suicide mortality rates per 100,000 (SMRs) in Japan consistently decreased from 2009 to 2019 but increased from 2020. The causes of these temporal SMR fluctuations remain to be clarified. Therefore, this study was conducted to identify the causalities underlying the recently transformed fluctuations of suicide mortality in Japan. Monthly suicide numbers disaggregated by sex and social standing, and political uncertainty indices, such as economic policy uncertainty (EPU) and government management instability (AENROP), were obtained from Japanese government databases. Interrupted time-series analysis was performed to analyze temporal fluctuations of SMRs disaggregated by sex/social standing associated with the three General Principles of Suicide Prevention Policy (GPSPP) periods and the COVID-19 pandemic. Panel data and vector autoregressive analyses were conducted to investigate causalities from political uncertainties to SMRs. During the first and second GPSPPs (2009-2017), all SMRs disaggregated by sex and social standing decreased, whereas those of unemployed females did not change. During the third GPSPP (2017-2022), decreasing trends in all SMRs were attenuated compared to previous periods. All female SMRs, except unemployed females, showed sharp increases synchronized with the pandemic outbreak. No male SMRs showed sharply increasing at the pandemic outbreak. SMRs of unemployed males/females drastically increased in the later periods of the pandemic, while SMRs of employed and multiple-person/single-person household males did not increase during the pandemic. SMR of unemployed males was positively related to AENROP but not EPU. Other male SMRs were positively related to EPU/AENROP. On the contrary, not all female SMRs were related to EPU/AENROP. Increasing AENROP generally contributed to increasing male SMRs throughout the observation period; however, susceptibility to AENROP and/or political information might have unexpectedly contributed to suppressing the sharply increasing male SMRs induced by large-scale social shocks (the COVID-19 pandemic outbreak) in Japan.

Duration of prehospital and in-hospital cardiopulmonary resuscitation and neurological outcome in paediatric out-of-hospital cardiac arrest

BackgroundBecause of their young age and lack of known comorbidities, paediatric patients with out-of-hospital cardiac arrest (OHCA) often undergo prolonged cardiopulmonary resuscitation (CPR). We aimed to determine the association between...

Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database.

The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92-3.63, p = 0.08). Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.

Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors used in Patients with DiabetesMellitus and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently become a standard treatment for heart failure and renal failure. The number of patients using these drugs is expected to increase further. However, no adverse drug event profiles have been published for the use of SGLT2i in patients without diabetes. To analyze and clarify the differences in adverse event profiles associated with the use of SGLT2i in patients with diabetes or heart failure using the Japanese Adverse Drug Event Report (JADER) database, a Japanese reporting system for adverse events. The JADER database, containing reports submitted between April 2004 and January 2024, was used. Our study focused on patients with diabetes or heart failure, analyzing adverse events associated with empagliflozin and dapagliflozin. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated for signal detection. We identified risks of adverse drug events such as ketoacidosis, urinary tract infection, dehydration, and acidosis in both patient groups. However, the risks of cerebral infarction and ischemic heart disease were identified only in patients with diabetes, while risks of renal dysfunction, hypoglycemia, and sepsis were identified only in those with heart failure. Adverse events should be managed appropriately for patients using SGLT2i, as the adverse event profiles differ between those with diabetes and those with heart failure. Understanding these differences is crucial for improving patient safety and optimizing treatment outcomes.

Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan.

SGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan. We conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12months. After 6months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01-0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30-0.84, P = 0.009) compared to DPP4i. SGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.

Association between Polypharmacy and Adverse Events in Patients with Alzheimer's Disease: An Analysis of the Japanese Adverse Drug Event Report Database (JADER).

Background and Objectives: Alzheimer's disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer's disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer's disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer's disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer's disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer's disease drugs and their combination patterns.

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study

ObjectivesLow-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. MethodsThis retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0–20.0 mg/kg/d) and low-dose (7.5–15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. ResultsAmong 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, −1.4 %; 95 % CI, −4.5–1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3–6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, −4.0 %; 95 % CI, −7.4 to −0.6 %; P = 0.020). ConclusionLow-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.