Treatment for patients with autosomal dominant polycystic kidney disease in the chronic kidney disease without kidney replacement therapy in real-world clinical practice: a descriptive retrospective cohort study.

BACKGROUND: In real-world clinical practice, treatments selected for patients with autosomal dominant polycystic kidney disease (ADPKD) in the chronic kidney disease (CKD) without kidney replacement therapy (KRT) have not been reported. This study investigated the oral treatments used in these patients and the changes in their use in recent years. Additionally, we studied the factors affecting tolvaptan dose reduction or discontinuation. METHODS: This retrospective cohort study was conducted using the medical records of 160 hospitals in Japan. Patients with ADPKD or polycystic kidney disease registered on the database between January 2014 and December 2020 were selected. Changes in prescription proportions over time were assessed using the Cochran-Armitage test. We focused on patients prescribed with >15 mg of tolvaptan daily to identify the factors related to its dose reduction or discontinuation and used Multivariate Cox regression analysis to evaluate them. RESULTS: Tolvaptan use in patients with ADPKD in the CKD without KRT stage has increased. As of 2020, 25% of patients were treated with tolvaptan. Overall, 3639 patients with ADPKD were enrolled in the database, of whom 156 were treated with tolvaptan. Of these, 64 patients (41%) reduced or discontinued tolvaptan during the observation period. The presence of an estimated glomerular filtration rate <60 mL/min/1.73 m2 at the beginning of the treatment was associated with a higher risk of tolvaptan dose reduction or discontinuation. CONCLUSION: The proportion of patients with ADPKD treated with high-dose tolvaptan is increasing. However, patients with late-stage CKD tended to reduce or discontinue tolvaptan.

Correction: Electronic Health Record-Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/40595.].

The association between intraoperative anesthesia methods used during gastric cancer surgery and long-term mortality: A retrospective observational study using a Japanese claims database.

PURPOSE: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. METHODS: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. RESULTS: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93). CONCLUSIONS: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy.

In-hospital mortality and cardiovascular treatment during hospitalization for heart failure among patients with schizophrenia: a nationwide cohort study.

AIMS: Schizophrenia is associated with cardiovascular disease (CVD) risk, and patients with schizophrenia are more likely to receive suboptimal care for CVD. However, there is limited knowledge regarding in-hospital prognosis and quality of care for patients with schizophrenia hospitalized for heart failure (HF). This study sought to elucidate the association between schizophrenia and in-hospital mortality, as well as cardiovascular treatment in patients hospitalized with HF. METHODS: Using the nationwide cardiovascular registry data in Japan, a total of 704,193 patients hospitalized with HF from 2012 to 2019 were included and stratified by age: young age, > 18 to 45 years (n = 20,289); middle age, >45 to 65 years (n = 114,947); and old age, >65 to 85 years (n = 568,957). All and 30-day in-hospital mortality as well as prescription of cardiovascular medications were assessed. After multiple imputation for missing values, mixed-effect multivariable logistic regression analysis was performed using patient and hospital characteristics with hospital identifier as a variable with random effects. RESULTS: Patients with schizophrenia were more likely to experience prolonged hospital stays, and incur higher hospitalization costs. In-hospital mortality for non-elderly patients with schizophrenia was significantly worse than for those without schizophrenia: the mortality rate was 7.6% vs 3.5% and the adjusted odds ratio (OR) was 1.96 (95% confidence interval (CI): 1.24-3.10, P = 0.0037) in young adult patients; 6.2% vs 4.0% and 1.49 (95% CI: 1.17-1.88, P < 0.001) in middle-aged patients. Thirty-day in-hospital mortality was significantly worse in middle-aged patients: the mortality rate was 4.7% vs 3.0% and an adjusted OR was 1.40 (95% CI: 1.07-1.83, P = 0.012). In-hospital mortality in elderly patients did not differ between those with and without schizophrenia. Prescriptions of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were significantly lower in patients with schizophrenia across all age groups. CONCLUSION: Schizophrenia was identified as a risk factor for in-hospital mortality and reduced prescription of cardioprotective medications in non-elderly patients hospitalized with HF. These findings highlight the necessity for differentiated care and management of HF in patients with severe mental illnesses.

Health-Related Quality of Life After Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: A Systematic Review and Meta-analysis.

BACKGROUND: There has been no meta-analysis of whether percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) improves health-related quality of life (HRQL) compared with OMT alone in patients with stable ischemic heart disease (SIHD). METHODS: We searched MEDLINE, Cochrane Central Registry of Controlled Trials, Embase, ClinicalTrials.gov, and International Clinical Trials Registry Platform in November 2022. We included randomized controlled trials (RCTs) that compared PCI with OMT vs OMT alone with HRQL in patients with SIHD. The primary outcome was the aggregated physical HRQL, including physical functioning using the Short Form (SF)-36 or RAND-36, physical limitation using the Seattle Angina Questionnaire (SAQ) or SAQ-7, McMaster Health Index Questionnaire, and Duke Activity Status Index within 6 months. Data were analyzed using a random effects model when substantial heterogeneity was identified or a fixed effect model otherwise. RESULTS: Among 14 systematically reviewed RCTs, 12 RCTs with 12,238 patients were meta-analyzed. Only 1 trial had a low risk of bias in all domains. PCI with OMT improved aggregated physical HRQL (standardized mean difference, 0.16; 95% confidence interval [CI], 0.1-0.23; P < 0.0001) at 6 months. Also, PCI with OMT improved physical functioning on the SF-36/RAND-36 (mean difference 3.65; 95% CI, 1.88-5.41) and physical limitation on the SAQ/SAQ-7 (mean difference, 3.09; 95% CI, 0.93-5.24) compared with OMT alone at 6 months. However, all of the aggregated physical HRQL domains were classified into small effects, and no HRQL domain exceeded the prespecified minimal clinically important difference. CONCLUSIONS: These findings showed that PCI with OMT improved HRQL compared with OMT alone in patients with SIHD, but the benefit was not large.

Effectiveness of intraoperative nicorandil in patients with a history of ischemic heart disease undergoing high-risk noncardiac surgery: a retrospective cohort study.

PURPOSE: Nicorandil is occasionally administered to prevent myocardial ischemia during the perioperative period in patients with ischemic heart disease (IHD); however, its effectiveness has not been clarified. In this study, we examined the effectiveness of intraoperative nicorandil administration in noncardiac surgery. METHODS: We identified patients with a history of IHD who had undergone high-risk noncardiac surgery between April 2015 and March 2020 from a nationwide in-patient database in Japan. The patients were divided into those who received nicorandil (nicorandil group) and those who did not (control group). The primary outcome was the 30-day in-hospital mortality. The secondary outcome was major adverse cardiovascular events (MACE), defined as the composite outcome of the 30-day in-hospital mortality, acute myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. One-to-one propensity score matching was performed. The outcomes were analyzed using a Cox proportional hazards model. RESULTS: Of 8037 patients, 2886 received nicorandil during surgery. After propensity score matching, 2554 pairs were analyzed. There was no significant difference in the 30-day in-hospital mortality (26 [1.02%] vs. 36 [1.41%]; hazard ratio [HR] 1.36; 95% confidence interval [CI] 0.82-2.26; P = 0.229) or incidence of MACE (42 [1.64%] vs. 55 [2.15%]; HR 1.24; 95% CI 0.86-1.93; P = 0.216) between the control and nicorandil groups. CONCLUSION: The findings of this study suggest that intraoperative nicorandil administration is not associated with the 30-day in-hospital mortality in high-risk noncardiac surgery.

Association between patient volume to cardiologist, process of care, and clinical outcomes in heart failure.

AIMS: The impact of hospital volume on clinical performance has been investigated by many researchers to date and thought that it is associated with quality of care and outcome for patients with heart failure (HF). This study sought to determine whether annual admissions of HF per cardiologist are associated with process of care, mortality, and readmission. METHODS AND RESULTS: Among the nationwide registry 'Japanese registry of all cardiac and vascular diseases - diagnostics procedure combination' data collected from 2012 to 2019, a total of 1 127 113 adult patients with HF and 1046 hospitals were included in the study. Primary outcome was in-hospital mortality, and secondary outcome was 30 day in-hospital mortality and readmission at 30 days and 6 months. Hospital and patient characteristics and process of care measures were also assessed. Mixed-effect logistic regression and Cox proportional-hazards model was used for multivariable analysis, and adjusted odds ratio and hazard ratio were evaluated. Process of care measures had inverse trends for annual admissions of HF per cardiologist (P < 0.01 for all measures: prescription rate of beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, mineralocorticoid receptor antagonist, and anticoagulant for atrial fibrillation). Adjusted odds ratio for in-hospital mortality was 1.04 (95% confidence interval (CI): 1.04-1.08, P = 0.04) and 30 day in-hospital mortality was 1.05 (95% CI: 1.01-1.09, P = 0.01) for interval of 50 annual admissions of HF per cardiologist. Adjusted hazard ratio for 30 day readmission was 1.05 (95% CI: 1.02-1.08, P < 0.01) and 6 month readmission was 1.07 (95% CI: 1.03-1.11, P < 0.01). Plots of the adjusted odds indicated 300 as the threshold of annual admissions of HF per cardiologist for substantial increase of in-hospital mortality risk. CONCLUSIONS: Our findings demonstrated that annual admissions of HF per cardiologist are associated with worse process of care, mortality, and readmission with the threshold for mortality risk increased, emphasizing the optimal proportion of patients admitted with HF to cardiologist for better clinical performance.

Electronic Health Record-Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial.

BACKGROUND: Clinical guidelines recommend regular serum lithium monitoring every 3 to 6 months. However, in the real world, only a minority of patients receive adequate monitoring. OBJECTIVE: This study aims to examine whether the use of the electronic health record (EHR)-nested reminder system for serum lithium monitoring can help achieve serum lithium concentrations within the therapeutic range for patients on lithium maintenance therapy. METHODS: We conducted an unblinded, single-center, EHR-nested, parallel-group, superiority randomized controlled trial comparing EHR-nested reminders with usual care in adult patients receiving lithium maintenance therapy for mood disorders. The primary outcome was the achievement of therapeutically appropriate serum lithium levels between 0.4 and 1.0 mEq/L at 18 months after enrollment. The key secondary outcomes are included as follows: the number of serum lithium level monitoring except for the first and final monitoring; exacerbation of the mood disorder during the study period, defined by hospitalization, increase in lithium dose, addition of antipsychotic drugs or mood stabilizers, or addition or increase of antidepressants; adherence defined by the proportion of days covered by lithium carbonate prescription during the study period. RESULTS: A total of 111 patients were enrolled in this study. A total of 56 patients were assigned to the reminder group, and 55 patients were assigned to the usual care group. At the follow-up, 38 (69.1%) patients in the reminder group and 33 (60.0%) patients in the usual care group achieved the primary outcome (odds ratio 2.14, 95% CI 0.82-5.58, P=.12). The median number of serum lithium monitoring was 2 in the reminder group and 0 in the usual care group (rate ratio 3.62; 95% CI 2.47-5.29, P<.001). The exacerbation of mood disorders occurred in 17 (31.5%) patients in the reminder group and in 16 (34.8%) patients in the usual care group (odds ratio 0.97, 95% CI 0.42-2.28, P=.95). CONCLUSIONS: We found insufficient evidence for an EHR-nested reminder to increase the achievement of therapeutic serum lithium concentrations. However, the number of monitoring increased with relatively simple and inexpensive intervention. The EHR-based reminders may be useful to improve quality of care for patients on lithium maintenance therapy, and they have potentials to be applied to other problems. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000033633; https://tinyurl.com/5n7wtyav.

Cardiac Rehabilitation for Patients With Stable Ischemic Heart Disease Without Revascularization　- Rationale and Design of a Single-Arm Pilot Study.

Background: Clinical practice guidelines strongly recommend optimal medical therapy (OMT), including lifestyle modification, pharmacotherapy, and exercise-based cardiac rehabilitation (CR), in patients with stable ischemic heart disease (SIHD). However, the efficacy and safety of CR in patients with SIHD without revascularization remain unclear. Methods and Results: The Prospective Registry of STable Angina RehabiliTation (Pre-START) study is a multicenter, prospective, single-arm, open-label pilot study to evaluate the efficacy and safety of CR on health-related quality of life (HRQL), exercise capacity, and clinical outcomes in Japanese patients with SIHD without revascularization. In this study, all patients will undergo guideline-based OMT and are encouraged to have 36 outpatient CR sessions within 5 months after enrollment. The primary endpoint is the change in the Seattle Angina Questionnaire-7 summary score between baseline and the 6-month visit; an improvement of ≥5 points will be defined as a clinically important change. Secondary endpoints include changes in other HRQL scores and exercise capacity between baseline and the 6-month visit, as well as clinical outcomes between enrollment and the 6-month visit. Conclusions: The Pre-START study will provide valuable evidence to elucidate the efficacy and safety of CR in patients with SIHD and indispensable information for a subsequent randomized controlled trial. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000045415) on April 1, 2022.

The Association Between Hypouricemia and Cardiometabolic Diseases: Analyzing Nationwide Data From Medical Checkup and Health Insurance Records.

OBJECTIVES: The aims of this study were to evaluate the association between hypouricemia and cardiometabolic diseases, such as hypertension, dyslipidemia, and reduced kidney function, and to explore the sex-specific optimal range for serum uric acid (sUA) associated with the lowest risk for these diseases. METHODS: In this cross-sectional study, we identified individuals with sUA data between April 2018 and March 2019 and recorded the frequency of cardiometabolic comorbidities according to sUA. Univariable and multivariable logistic regression analyses were performed for the overall population and after classifying by sex to assess the association between sUA and cardiometabolic comorbidities. RESULTS: Among 796,508 individuals, a J-shaped association was observed between the sUA level and cardiometabolic diseases in the overall population. The adjusted odds ratios (95% confidence interval) for hypertension, dyslipidemia, and reduced renal function in individuals with sUA ≤1.0 mg/dL compared with those with sUA ranging between 2.1 and 3.0 mg/dL were 1.38 (1.13-1.69), 1.52 (1.30-1.78), and 2.17 (1.47-3.20), respectively. A J-shaped association between sUA and hypertension was observed only in women. The optimal range of sUA associated with the lowest risk for hypertension was assumed to be <6 mg/dL in men and 1-4 mg/dL in women. A J-shaped association between the sUA and dyslipidemia and reduced renal function was observed in both men and women. The optimal range of sUA for dyslipidemia and reduced renal function was approximately 2-5 mg/dL in men and 1-4 mg/dL in women. CONCLUSIONS: Excess and extremely low uric acid levels may be related to an increased cardiometabolic risk.

Intensive care unit versus high-dependency care unit admission on mortality in patients with septic shock: a retrospective cohort study using Japanese claims data.

BACKGROUND: Septic shock is a common and life-threatening condition that requires intensive care. Intensive care units (ICUs) in Japan are classified into ICUs and high-dependency care units (HDUs), depending on presence of full-time certified intensivists and the number of assigned nurses. Compared with other developed countries, there are fewer intensive care beds and certified intensivists in Japan; therefore, non-intensivists often treat patients with septic shock in HDUs. It is unknown where we should treat patients with septic shock because no studies have compared the clinical outcomes between ICU and HDU treatment. This study aimed to elucidate which units should admit patients with septic shock by comparing mortality data and resource use between ICU and HDU admissions. METHODS: In this retrospective cohort study, we used a nationwide Japanese administrative database to identify adult patients with septic shock who were admitted to ICUs or HDUs between January 2010 and February 2021. The patients were divided into two groups, based on admittance to ICU or HDU on the day of hospitalization. The primary outcome was 30-day all-cause mortality adjusted for covariates using Cox regression analyses; the secondary outcomes were the length of ICU or HDU stay and length of hospital stay. RESULTS: Of the 10,818 eligible hospitalizations for septic shock, 6584 were in the ICU group, and 4234 were in the HDU group. Cox regression analyses revealed that patients admitted to the ICUs had lower 30-day mortality (adjusted hazard ratio: 0.89; 95% confidence interval: 0.83-0.96; P = 0.005). Linear regression analyses showed no significant difference in hospital length of stay or ICU or HDU length of stay. CONCLUSIONS: An association was observed between ICU admission and lower 30-day mortality in patients with septic shock. These findings could provide essential insights for building a more appropriate treatment system.

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study.

BACKGROUND: Although several studies have compared the effectiveness and safety of rivaroxaban and apixaban in patients with venous thromboembolism (VTE), direct comparison of these drugs with edoxaban is lacking. OBJECTIVE: We compared the effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with VTE. PATIENTS/METHODS: In this retrospective cohort study using a Japanese hospital administrative database, we identified three mutually exclusive groups of patients with VTE beginning treatment with edoxaban, rivaroxaban, or apixaban. Primary effectiveness outcome was recurrent VTE, and principal safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. Subjects were followed for up to 180 days. Baseline characteristics among groups were balanced using propensity score matching weights. RESULTS: Three thousand three hundred sixty-nine edoxaban, 1592 rivaroxaban, and 1998 apixaban initiators were identified. There were no significant differences among the three drugs in the prevention of recurrent VTE (adjusted incidence rate ratio [aIRR], 0.77; 95% confidence interval [CI], 0.45-1.30 for edoxaban vs. rivaroxaban; aIRR, 0.92; 95% CI, 0.54-1.56 for edoxaban vs. apixaban; and aIRR, 1.20; 95% CI, 0.69-2.10 for rivaroxaban vs. apixaban), or in the risk of intracranial hemorrhage or gastrointestinal bleeding (aIRR, 1.57, 95% CI, 0.85-2.90 for edoxaban vs. rivaroxaban; aIRR, 1.30, 95% CI, 0.76-2.23 for edoxaban vs. apixaban; and aIRR, 0.83, 95% CI, 0.42-1.64 for rivaroxaban vs. apixaban). CONCLUSIONS: In routine care, edoxaban, rivaroxaban, and apixaban appear to have similar effectiveness and safety in the treatment of VTE.

Comparison of noninvasive follow-up testing in patients after percutaneous coronary intervention with drug-eluting stent implantation.

BACKGROUND: This study sought to elucidate the trend of noninvasive follow-up testing in Japan and its impact on subsequent resource use and clinical outcomes after drug-eluting stent (DES) implantation. METHOD: This retrospective study used data from a Japanese nationwide administrative database. We performed trend analyses for patients who underwent DES implantation from 2013 to 2019 and further analyzed who received at least one noninvasive follow-up testing. We compared stress electrocardiography (ECG), coronary computed tomography angiography (CCTA), and myocardial perfusion imaging (MPI) and outcomes using inverse probability weighting with generalized propensity scores. Primary outcomes included subsequent coronary angiography (CAG) and re-percutaneous coronary intervention (re-PCI). RESULTS: In trend analysis, 23.7% of patients underwent noninvasive follow-up testing, and 47.5% underwent CAG without preceding noninvasive follow-up testing. Total follow-up tests and CAG declined, whereas stress ECG, CCTA, and MPI increased (p for trend <0.001 for all). Among 32,850 patients who underwent noninvasive follow-up tests, 7465 (22.7%), 12,617 (38.4%), and 12,768 (38.9%) patients underwent stress ECG, CCTA, and MPI, respectively. Both CCTA and MPI were associated with a lower risk of subsequent CAG [CCTA vs. stress ECG, hazard ratio (HR): 0.28, 95% confidence interval (CI): 0.26 to 0.31; MPI vs. stress ECG, HR: 0.61, 95% CI: 0.57-0.66], but both CCTA and MPI were associated with a higher risk of re-percutaneous coronary intervention (CCTA vs. stress ECG, HR: 1.21, 95% CI: 1.06-1.37; MPI vs. stress ECG, HR, 1.25; 95% CI, 1.10-1.43) than stress ECG. CONCLUSIONS: More than half of the patients had undergone a follow-up test after DES implantation within two years of PCI with DES implantation. Total follow-up tests and CAG decreased, but noninvasive follow-up tests increased. Neither CCTA nor MPI are recommended for initial follow-up testing after PCI because they were associated with the higher risk of re-PCI than stress ECG.

Complications associated with the use of enzyme-inducing and non-enzyme-inducing anti-seizure medications in the Japanese population: A retrospective cohort study.

OBJECTIVE: Enzyme-inducing anti-seizure medications (EIASMs) may contribute to the development of complications such as fracture and cardiovascular disease. The objective of the study was to determine whether the use of EIASMs is associated with a higher risk of fracture and cardiovascular outcome in young Japanese patients with epilepsy. METHOD: Adult patients diagnosed with epilepsy and initiated a monotherapy with an anti-seizure medication (ASM) between 2008 and 2018 were included in the study. The primary outcomes were the occurrence of acute myocardial infarction (AMI) or stroke. The secondary outcome was fracture. We performed a propensity score-matched analysis (1:1) to control for imbalances in patient characteristics, and the matched hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULT: Of the 7115 eligible patients, 626 (8.79%) initiated treatment with EIASMs. The median age of the patients was 44 years (interquartile range: 31-54 years), and 56.2% were male. Propensity score matching generated 626 matched pairs of patients treated with EIASMs and non-EIASMs. There were no significant differences in the risk of stroke (EIASM group: n = 28[4.47%], non-EIASM group: n = 22[3.51%], HR: 1.47, 95% CI: 0.79-2.72, p = 0.22) or fracture (EIASM group: n = 7[1.12%], non-EIASM group: n = 5[0.80%], HR: 1.00, 95% CI: 0.29-3.45, p = 1.00) between the two groups. The hazard ratio for the occurrence of AMI could not be calculated due to the small number of events (EIASM group: n = 0[0.00], non-EIASM group: n = 2[0.32]). SIGNIFICANCE: Our cohort study did not find increased risk of the occurrence of stroke, AMI, or fracture hospitalization with the use of enzyme-inducing ASMs. Although the findings suggested that exposure to EIASMs does not appear to increase the risk of complications in young patients, caution should be taken as patients with epilepsy tend to take medication in the long run.

Association between antiulcer agents and Clostridioides difficile infection in patients receiving antibiotics: A retrospective cohort study using the diagnosis procedure combination database in Japan.

OBJECTIVES: To evaluate baseline risk for hospital onset Clostridioides difficile infection (HO-CDI) and the association with the use of antiulcer agents among patients undergoing antibiotic therapy in Japan. METHODS: We conducted a retrospective cohort study using Japanese Diagnosis Procedure Combination database. Between July 2018 and January 2019, patients aged ≥18 years were included if they started antibiotics within two days of hospital admission. We defined exposure as proton pump inhibitors or histamine 2 receptor antagonists starting from day 2 to day 4 and the primary outcome as HO-CDI within 30 days. We performed multivariable analyses with complete cases using the propensity score (inverse probability treatment weighting [IPTW]) and several sensitivity analyses. RESULTS: In total, 87,137 patients were included. The median age was 78 years; 52.0% were men, and 23.6% received antiulcer agents. Within 30 days of admission, HO-CDI were observed in 0.41% and 0.26% of the antiulcer agent and control groups, respectively. IPTW revealed a positive association between antiulcer agents and HO-CDI (adjusted odds ratio, 1.33; 95% confidence interval [CI]: 1.13, 1.56). In the IPTW method, the risk difference was smaller (0.09%, 95% CI: 0.04%, 0.15%). CONCLUSION: The use of antiulcer agents in patients with antibiotics was associated with HO-CDI in Japan. However, the baseline risk and the difference in HO-CDI event rates were small; thus, as per several clinical practice guidelines, it is important to monitor antiulcer agent use and discontinue unnecessary use. The baseline risk should be considered when clinically evaluating the association between antiulcer agents and HO-CDI.

Temporal trends in the prevalence and characteristics of hypouricaemia: a descriptive study of medical check-up and administrative claims data.

We aimed to describe temporal trends in the prevalence and characteristics of hypouricaemia. We analysed medical check-up and administrative claims data to calculate hypouricaemia prevalence from 2009 to 2019. Then, using data from 2018 to 2019, we compared the characteristics of individuals with and without hypouricaemia. We also compared the characteristics of those with lower (serum uric acid [sUA] ≤ 1.0 mg/dL) and higher (1.0 mg/dL < sUA ≤ 2.0 mg/dL) hypouricaemia. In total, 1,600,290 subjects underwent medical check-ups. The age-adjusted prevalence of hypouricaemia remained stable at 0.2% overall (men, 0.1%; women, 0.4%). We identified 1704 subjects with hypouricaemia (598 men and 1106 women) among 796,508 subjects and studied their characteristics. The proportion of most pre-existing diseases, including urinary stones, was lower in those with hypouricaemia than in those without hypouricaemia. Cardio-metabolic diseases and Parkinson's disease were more frequent in men with hypouricaemia than those without hypouricaemia. Women with hypouricaemia tended to have healthier characteristics. Hypertension and dyslipidaemia were more common in the lower hypouricaemia group than in the higher hypouricaemia group. The age-adjusted prevalence of hypouricaemia remained stable over 10 years. The characteristics of hypouricaemia subjects appear to differ between the sexes and between lower and higher hypouricaemia groups. Key Points • The prevalence of hypouricaemia remained almost unchanged over 10 years. • Cardio-metabolic diseases and Parkinson's disease were more frequent in men with hypouricaemia than in those without hypouricaemia. • Subjects with extremely low serum urate (sUA ≤ 1.0 mg/dL) appeared to have higher cardio-metabolic disease risks. • Routine checks of sUA could be useful in screening or predicting these conditions.

Appropriateness of Percutaneous Coronary Intervention Performed by Japanese Expert Operators in Patients With Chronic Total Occlusion.

BACKGROUND: The appropriateness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions has rarely been investigated.Methods and Results: The Japanese CTO-PCI Expert Registry enrolled consecutive patients undergoing CTO-PCI carried out by highly experienced Japanese CTO specialists who performed more than 50 CTO-PCIs per year and 300 CTO-PCIs in total. This study included patients undergoing CTO-PCI between January 2014 and December 2019. The appropriateness, trends, and differences among the procedures performed by the operators using the 2017 appropriate use criteria were analyzed. Furthermore, we performed a logistic regression analysis to assess whether the appropriateness was associated with in-hospital major adverse cardiovascular and cerebrovascular events (MACCE). Of the 5,062 patients who underwent CTO-PCI, 4,309 (85.1%) patients who did not undergo the non-invasive stress test were classified as having no myocardial ischemia. Of the total cases, 3,150 (62.2%) were rated as "may be appropriate," and 642 (12.7%) as "rarely appropriate" CTO-PCI cases. The sensitivity analyses showed that the number (%) of "may be appropriate" ranged from 4,125 (57.8%) to 4,744 (66.4%) and the number of "rarely appropriate" ranged from 843 (11.8%) to 970 (13.6%) among best and worst scenarios. CONCLUSIONS: In a large Japanese CTO-PCI registry, approximately 13% of CTO-PCI procedures were classified as "rarely appropriate". Substantial efforts would be required to decrease the number of "rarely appropriate" CTO-PCI procedures.

Association of short-term exposure to air pollution with myocardial infarction with and without obstructive coronary artery disease.

BACKGROUND: Air pollution including particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) increases the risk of acute myocardial infarction. However, whether short-term exposure to PM2.5 triggers the onset of myocardial infarction with nonobstructive coronary arteries, compared with myocardial infarction with coronary artery disease, has not been elucidated. This study aimed to estimate the association between short-term exposure to PM2.5 and admission for acute myocardial infarction, myocardial infarction with coronary artery disease, and myocardial infarction with nonobstructive coronary arteries. DESIGN: This was a time-stratified case-crossover study and multicenter validation study. METHODS: This study used a nationwide administrative database in Japan between April 2012-March 2016. Of 137,678 acute myocardial infarction cases, 123,633 myocardial infarction with coronary artery disease and 14,045 myocardial infarction with nonobstructive coronary arteries were identified by a validated algorithm combined with International Classification of Disease (10th revision), diagnostic, and procedure codes. Air pollutants and meteorological data were obtained from the monitoring station nearest to the admitting hospital. RESULTS: In spring (March-May), the short-term increase of 10 µg/m3 in PM2.5 2 days before admission was significantly associated with admission for acute myocardial infarction, myocardial infarction with nonobstructive coronary arteries, and myocardial infarction with coronary artery disease after adjustment for meteorological variables (odds ratio 1.060, 95% confidence interval 1.038-1.082; odds ratio 1.151, 1.079-1.227; odds ratio 1.049, 1.026-1.073, respectively), while the association was not significant in other variables. These associations were also observed after adjustment for other co-pollutants. The risk for myocardial infarction with nonobstructive coronary arteries (vs myocardial infarction with coronary artery disease) was associated with an even lower concentration of PM2.5 under the current environmental standards. CONCLUSIONS: This study showed the seasonal difference of acute myocardial infarction risk attributable to PM2.5 and the difference in the threshold of triggering the onset of acute myocardial infarction subtype.