Efficacy of the bleeding risk scoring system for optimal prophylactic anticoagulation therapy of venous thromboembolism in trauma patients: a single-center, retrospective, observational cohort study.

BACKGROUND: We developed a bleeding risk scoring system (BRSS) using prophylactic anticoagulation therapy to comprehensively assess the risk of venous thromboembolism (VTE) in trauma patients. This study evaluated the usefulness of this system in trauma patients, with a focus on minimizing the rate of bleeding events associated with prophylactic anticoagulation therapy. METHODS: We retrospectively evaluated the efficacy of BRSS in trauma patients who received prophylactic anticoagulation therapy for VTE at the Kitasato University Hospital Emergency and Critical Care Center between April 1, 2015, and August 31, 2020. To compare the incidence of bleeding events, patients were divided into two groups: one group using the BRSS (BRSS group) and another group not using the BRSS (non-BRSS group). RESULTS: A total of 94 patients were enrolled in this study, with 70 and 24 patients assigned to the non-BRSS and BRSS groups, respectively. The major bleeding event rates were not significantly different between the two groups (BRSS group, 4.2%; non-BRSS group, 5.7%; p = 1.000). However, minor bleeding events were significantly reduced in the BRSS group (4.2% vs.27.1%; p = 0.020). Multivariate logistic regression analysis showed that BRSS was not an independent influencing factor of major bleeding events (odds ratio, 0.660; 95% confidence interval: 0.067-6.47; p = 0.721). Multivariate logistic regression analysis showed that BRSS was an independent influencing factor of minor bleeding events (odds ratio, 0.119; 95% confidence interval: 0.015-0.97; p = 0.047). The incidence of VTE did not differ significantly between groups (BRSS group, 4.2%; non-BRSS group, 8.6%; p = 0.674). CONCLUSIONS: BRSS may be a useful tool for reducing the incidence of minor bleeding events during the initial prophylactic anticoagulation therapy in trauma patients. There are several limitations of this study that need to be addressed in future research.

Investigating effective methods of clinical pharmacy training on oncology for community pharmacists: An observational study.

INTRODUCTION: Kitasato University Hospital offers a training course for community pharmacists that focus on advanced pharmacy management care in outpatient cancer chemotherapy. The objective of this training program is to facilitate the transition from general to oncology certification for community pharmacists with limited experience in outpatient oncology to support the acquisition of an oncology specialty. AIM: To evaluate the relationship between the changes in awareness, knowledge, and self-assessment that advanced pharmacy management care traineeship in an outpatient oncology unit for community pharmacists brings to trainees and the duration of training. METHODS: A quantitative text analysis was conducted of the daily training reports of six community pharmacists who had participated previously in the training course and had received in-service training in oncology for at least 30 days. The pre- and post-training results of the knowledge tests and self-assessments of confidence, understanding, and performance were compared. This study was approved by the Research Ethics Committee of Kitasato Institute Hospital in October 2019 (Study No. 19044). RESULTS: The terms Prescription, Recommendation were extracted from the daily report after the 21st day of oncology in-service training. Furthermore, factors such as knowledge of cancer pharmacotherapy, confidence in patient education regarding the side effects of chemotherapy, and understanding of the work of pharmacists in outpatient cancer chemotherapy significantly increased at the end of the training. CONCLUSIONS: Community pharmacists with limited experience in outpatient oncology could improve their knowledge, understanding, and awareness of outpatient oncology patient care through 30 days of in-service oncology training in a hospital setting. The issues that emerged included training pharmacists to send follow-up documents on the patients' side effects and medication status as well as developing the literature search environment in community pharmacies.

Smoking cessation in the elderly as a sign of susceptibility to symptomatic COVID-19 reinfection in the United States.

Background: We aimed to clarify the relationship between coronavirus disease 2019 (COVID-19) reinfection and basic disease and smoking status. Methods: The electronic health records of 165,320 patients with COVID-19 from January 1, 2020, to August 27, 2021, were analyzed. Data on age, race, sex, smoking status (never, current, former), and basic disease were analyzed using Cox proportional hazard models. Results: In total, 6,133 patients (3.7%) were reinfected. The overall reinfection rate for never, current, and former smokers was 4.2, 3.5, and 5.7%, respectively. Although the risk of reinfection was highest among former smokers aged ≥65 years (7.7% [422/5,460]), the reinfection rate among current smokers aged ≥65 years was 6.2% (341/5,543). Among reinfected patients, the number of basic diseases was higher in former smokers (2.41 ± 1.16) than in current (2.28 ± 1.07, P = 0.07) and never smokers (2.07 ± 1.05, P < 0.001). Former smokers who are older may have been exposed to factors that increase their risk of symptomatic COVID-19 reinfection.

Real-world risk of lower-limb amputation associated with sodium-glucose cotransporter 2 inhibitors versus metformin: A propensity score-matched model analysis in Japan.

AIMS/INTRODUCTION: We aimed to clarify the real-world risk of lower-limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium-glucose cotransporter 2 inhibitors (SGLT2is). MATERIALS AND METHODS: We carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower-limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents. RESULTS: Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80-2.24). However, female sex (HR 2.78, 95% CI 1.12-6.94) and use of strong statins (HR 2.68; 95% CI 1.18-8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group. CONCLUSIONS: SGLT2is might not be related to an increased risk of lower-limb amputation in patients with type 2 diabetes in real-world clinical practice. The possible increased risk of SGLT2is-associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable.

The change rate in serum nitric oxide may affect lenvatinib therapy in hepatocellular carcinoma.

BACKGROUND: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). METHODS: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO3-) to nitrite (NO2-) with nitrate reductase, followed by quantitation of NO2- based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE. RESULTS: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively). CONCLUSION: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.

Risk Factors for Non-Adherence to Medications That Affect Surgery: A Retrospective Study in Japan.

Purpose: Data on risk factors for non-adherence to doctors' and pharmacists' instructions to discontinue medications prior to surgery are lacking. This study aimed to identify characteristics and risk factors for such non-adherent patients. Patients and Methods: Data (including patient age, sex, prescription medications, comorbidities, presence of roommate at home, and number of days between receiving instruction and surgery) of 887 patients who used medications affecting surgery at a university hospital from April 2017 to March 2020 were retrospectively evaluated. The primary endpoint was to investigate the rate of non-adherence and to explore independent risk factors for non-adherence (with age categorized as ≥65 [versus <65] years). Secondary endpoints included analysis of limited number of departments subgroup and a sensitivity analysis (with age categorized as ≥75 [versus <75] years) to confirm the robustness of the primary endpoint results. Independent risk factors for non-adherence were identified using logistic regression analysis. Results: The non-adherence rate was 11.4% (n=101/887), median age (interquartile range) at admission was 73 (70-79) years, and proportion of male patients was 81.2% (n=82). The main analysis adjusted for age ≥65 (versus <65) years showed age as a risk factor for increased non-adherence (adjusted odds ratio: 2.1, 95% confidence interval: 1.09-4.05; p=0.027). However, analyses adjusted for departments (other than urology, gynecology, and breast surgery, with a large sex bias in hospitalized patients) and for age ≥75 (versus <75) years showed no such risk. Conclusion: Age ≥65 years was associated with a higher risk of non-adherence to medications that should be discontinued before surgery. It is important for doctors and pharmacists to ensure that patients at high risk for non-adherence are aware of the importance of adherence. Our findings may help identify patients at high risk for non-adherence to such medications.

Internal Validation of a Risk Scoring System for Venous Thromboembolism After Total hip or Knee Arthroplasty.

We developed a computerized clinical decision support system (CCDSS) for venous thromboembolism (VTE) risk assessment. We aimed to demonstrate its relevance and evaluate associations between risk level and VTE incidence in patients undergoing total hip/knee arthroplasty. In this case-control study, VTE was confirmed using ultrasonography/computed tomography angiography in 1098 adults at a tertiary care hospital over five years (2013-2018). Postoperative VTE incidence was classified into three risk levels (moderate, high, and highest). The overall VTE incidence was 11.7%, which increased with a risk level of 0%, 5.8%, and 12.8% in moderate-risk, high-risk, and highest-risk patients, respectively. Highest-risk patients were significantly more likely to develop VTE than high-risk patients (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.2-5.5; p = 0.01). VTE development was more likely in patients with risk scores ≥4 relative to those with risk scores of 2-3 (OR 1.8; 95% CI 1.2-2.7; p = 0.003) and -1 to 1 (OR 3.3; 95% CI 1.6-7.7; p < 0.001). This study indicates that risk level and VTE incidence are associated; our scoring system appears useful for patients undergoing total hip/knee arthroplasty.

Serum concentration of oral midazolam as pediatric preanesthetic medication and factors related to the sedation level.

BACKGROUND: Preanesthetic medication is important to eliminate surgical anxiety in pediatric patients and facilitate their smooth transfer to the operating room. Midazolam is the most commonly used preanesthetic medication. However, it has been reported that the sedative effect varies from patient to patient. In this study, the pharmacokinetics of midazolam were examined, and the aim was to assess the factors affecting the quality of sedation. METHODS: The participants were children ranging in age from 6 months to 8 years scheduled for surgery. Midazolam 0.5 mg/kg was administered orally 30 min before entering the operating room, and the sedation level was evaluated at the time of mask application. Blood was collected after slow induction, and the serum concentration of midazolam was measured using high-performance liquid chromatography. RESULTS: A total of 98 patients were registered. There was no difference in serum concentrations between the effective sedation group and the ineffective sedation group (48.0 vs. 49.1 ng/mL), regardless of the effect of midazolam. Percentages of ineffective sedation by age (0 to 7 years) were 66.6%, 60%, 33.3%, 11.1%, 0%, 0%, 12.5%, and 0%, respectively. On multivariate logistic regression analysis, siblings (OR = 3.9, CI: 1.1-14.0, p = .03) and age (OR = 3.2, CI:1.2-8.5, p = .02) were related to an insufficient sedative effect. CONCLUSION: The serum concentration of oral midazolam reached effective levels even in patients in whom the sedative effect was inadequate. It is important to manage the perioperative period with appropriate concurrent premedication taking into account patient age and social background characteristics. CLINICAL TRIAL REGISTRATION: Clinical trial registry: UMIN R000052504.

Timing of re-dosing based on population pharmacokinetic-pharmacodynamics target attainment analysis of cefmetazole in subjects undergoing lower gastrointestinal surgery.

INTRODUCTION: This study was conducted to evaluate the population pharmacokinetics of prophylactic cefmetazole sodium (CMZ) based on the serum concentrations and establish a pharmacodynamics target concentration exceeding the minimum inhibitory concentration (MIC) to design the re-dosing interval. METHODS: Serum (n = 362) samples from 107 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index obtained was regarded as the probability of maintaining CMZ serum trough exceeding the minimal inhibitory concentration (MIC) of 2 mg/L. This MIC was chosen to account for methicillin-susceptible Staphylococcus aureus (MSSA), E. coli, and Klebsiella pneumoniae RESULTS: The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance and body weight were identified as significant covariates influencing the central clearance and volume of distribution in the central compartment. The probability of achieving serum concentrations exceeding the MIC90 for MSSA, E. coli, and Klebsiella pneumoniae for a 1 g dose with a 10 min intravenous infusion was above 90% except for good renal function (CLcr â‰§ 95 mL/min) at 2 h after the initial dose. For patients with good renal function (CLcr â‰§ 95 mL/min), a CMZ of 2 g re-dosing interval seemed necessary to meet the achievement probability. In patients with impaired renal function (CLcr ≤20 mL/min), the probability of achievement exceeded 90% even when the dosing interval was extended to 8 h. CONCLUSIONS: We evaluated re-dosing intervals based on the population pharmacokinetics. Re-dosing intervals should be determined based on renal function.

Evaluation of a carbapenem antimicrobial stewardship program and clinical outcomes in a Japanese hospital.

INTRODUCTION: Microorganisms can evolve and become resistant to antimicrobials, and this is known as antimicrobial resistance (AMR). Inappropriate use of antibiotics contributes to AMR, and antimicrobial stewardship programs have been developed to mitigate AMR. The Appropriate Use of Carbapenems Program was implemented in March 2019 in a university hospital and its effect was evaluated. METHODS: We conducted a prospective audit and feedback on carbapenems at the time of prescription daily. Additionally, we compared a monthly survey of the total days of therapy (DOTs) per 1000 patient-days for carbapenems, piperacillin/tazobactam, and fluoroquinolones. The susceptibility of Pseudomonas aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin was tested before (January 2018 to February 2019) and after (March 2019 to December 2020) the intervention. RESULTS: The monthly median DOTs of carbapenem usage decreased after the intervention; carbapenem use immediately declined during the intervention period. The monthly median DOTs of piperacillin/tazobactam and fluoroquinolones also decreased and continued to decline significantly after the intervention. Susceptibility of P. aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin did not change significantly during the study. CONCLUSION: The implementation of the Appropriate Use of Carbapenems Program was effective in reducing the use of broad-spectrum antibiotics and maintaining the antibiotic susceptibility of P. aeruginosa.

Population Pharmacokinetic-Pharmacodynamic Target Attainment Analysis of Flomoxef in the Serum and Liver Tissue of Patients Undergoing Hepatic Resection.

The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (n = 210) and liver tissue samples (n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CLCR) was identified as a significant covariate influencing total clearance when CLCR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.

Initial trough concentration may be beneficial in preventing linezolid-induced thrombocytopenia.

We assessed whether prospective therapeutic drug monitoring to optimise the therapeutic range could prevent linezolid-induced thrombocytopenia. This prospective interventional study was conducted from September 2017 to October 2020 among 37 adult patients receiving linezolid. Patients were administered one of the following two initial dosages: 600 mg twice or once daily for patients with a creatinine clearance rate of ≥50 or <50 mL/min, respectively. Linezolid dosage adjustment was performed on days 3-5 based on the trough concentration. The serum linezolid levels in 22 and 15 patients were within and above the therapeutic range (2-7 µg/mL), respectively. The incidence of thrombocytopenia was significantly lower among patients whose linezolid levels were within the therapeutic range (4.5%;1/22) than in those whose levels were above the therapeutic range (80%; 12/15). It is important to maintain the linezolid level within the therapeutic range at the first therapeutic drug monitoring to prevent thrombocytopenia.

Acute kidney injury in Japanese type 2 diabetes patients receiving sodium-glucose cotransporter 2 inhibitors: A nationwide cohort study.

The present retrospective study aimed to identify factors associated with an increased risk of acute kidney injury in Japanese patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors. We identified 171,622 patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors; among them, 476 (0.3%) patients developed acute kidney injury. The hazard ratio for acute kidney injury occurrence risk was analyzed using a Cox proportional hazards model adjusted for patient characteristics at baseline and use of concomitant agents. In the adjusted model, patients who developed acute kidney injury were mostly men, aged ≥65 years, had lower body mass index, had a history of heart failure and used diuretics more frequently than those who did not. These findings suggest that associated clinical risk factors should be thoroughly evaluated before administering sodium-glucose cotransporter 2 inhibitors to minimize acute kidney injury onset.

Association of serum and fat tissue antibiotic concentrations with surgical site infections in lower gastrointestinal surgery.

BACKGROUND: During surgery, the effectiveness of perioperative prophylactic antibiotic administration against surgical site infections is inferred from serum concentrations and not from tissues where local infections occur. This study aimed to measure the serum and tissue concentrations of cefmetazole in colorectal surgery cases to clarify whether there is an association between the incidence of surgical site infections and antibiotic concentrations. METHODS: This prospective cohort study was performed at a single tertiary care center. The data of 105 patients who underwent colorectal surgery between October 2017 and September 2019 were evaluated. The primary outcome was the incidence of surgical site infections. Univariate analysis was performed to investigate the association between surgical site infections, perioperative factors, and the serum and tissue concentrations of cefmetazole. RESULTS: The incidence of surgical site infections was 13/105 (12.4%). Cefmetazole concentrations were measured at initial incision (serum; 101 vs 93.1 mg/L, P = .75, subcutaneous fat tissue; 2.8 vs 3.7 mg/g, P = .15), intestinal resection (serum; 35.1 vs 36.7 mg/L, P = .63, mesenteric adipose tissue; 1.3 vs 1.7 mg/g, P = .55), and at skin closure (serum; 34.5 vs 44.8 mg/L, P = .18, subcutaneous fat tissue; 1.0 vs 2.2 mg/g, P = .09). In univariate analysis with P ≤ .10, cefmetazole concentration in subcutaneous fat tissue at skin closure was found to be a significant risk factor for surgical site infections. Age, additional intraoperative administration of cefmetazole, and creatinine clearance were also significant risk factors for the occurrence of surgical site infections. CONCLUSION: Low subcutaneous fat cefmetazole concentrations at skin closure during gastrointestinal operations may also be involved in the occurrence of surgical site infections.

Development and validation of an equation to predict the incidence of coronary heart disease in patients with type 2 diabetes in Japan.

OBJECTIVE: In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation. RESULTS: By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities.

Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States.

The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0-4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470-34.600] and 55.803 [12.761-244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.

Population Pharmacokinetic and Pharmacodynamic Target Attainment Analysis of Cefazolin in the Serum and Hip Joint Capsule of Patients Undergoing Total Hip Arthroplasty.

The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in patients undergoing total hip arthroplasty and to establish the pharmacodynamic target concentration exceeding the MIC for designing an effective dosing regimen for serum and the hip joint capsule. We analyzed 249 serum samples and 125 hip joint capsule samples from 125 individuals using a nonlinear mixed-effects model. The pharmacodynamic index target value obtained from our results indicates the probability of maintaining CFZ trough and hip joint capsule concentrations exceeding the MIC of 1 mg/liter to account for methicillin-susceptible S. aureus (MSSA). We estimated the population pharmacokinetics using a two-compartment model. The estimated population pharmacokinetic parameters were as follows: clearance (CL) (liters/h) = 1.46 × (creatinine clearance [CLcr] [ml/min]/77)0.891, volume of distribution of the central compartment (Vc) (liters) = 7.5, central-hip joint capsule compartment clearance (Q) (liters/h) = 3.38, and volume of distribution in the hip joint capsule compartment (VJC) (liters) = 36.1. The probability of achieving concentrations exceeding the MIC90 for MSSA was approximately 100% for serum and 100% for the hip joint capsule at 3 h after the initial dose. Our findings suggest that population-based parameters are useful for evaluating CFZ pharmacokinetics and that individual dosages should be determined based on the dosage regimen that achieves and maintains adequate tissue CFZ concentration.

On-label use of sodium-glucose cotransporter 2 inhibitors might increase the risk of diabetic ketoacidosis in patients with type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin-treated type 1 diabetes patients administered sodium-glucose cotransporter 2 (SGLT2) inhibitors in real-world clinical practice. MATERIALS AND METHODS: We carried out a real-world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin-treated adult type 1 diabetes patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in type 1 diabetes patients using SGLT2 inhibitors in an 'on-label' manner. Cox multivariate regression analyses were carried out to determine clinical factors linked to SGLT2 inhibitor-associated DKA. RESULTS: Of 11,475 type 1 diabetes patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person-years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio 1.66, 95% confidence interval 1.33-2.06; P < 0.001). The mean time until DKA onset in SGLT2 inhibitor-treated type 1 diabetes patients was 30.6 ± 30.1 days. The risk of SGLT2 inhibitor-associated DKA increased in type 1 diabetes patients irrespective of sex, age or body mass index. However, the risk did not increase in type 1 diabetes patients receiving continuous subcutaneous insulin infusion, which warrants further investigation because of the small number of type 1 diabetes patients receiving continuous subcutaneous insulin infusion. CONCLUSIONS: 'On-label' SGLT2 inhibitor use might increase DKA risk among insulin-treated type 1 diabetes patients irrespective of sex, age or body mass index. Both type 1 diabetes patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.

Real-world risk of hypoglycemia-related hospitalization in Japanese patients with type 2 diabetes using SGLT2 inhibitors: a nationwide cohort study.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are believed to lower glucose levels and inhibit cardiovascular events related to type 2 diabetes (T2D). To maximize their benefits, the risk of resultant hypoglycemia has to be minimized; however, the magnitude of this risk remains unclear. Here, we aimed to identify clinical factors linked to an increased risk of hypoglycemia among Japanese patients with T2D and treated with SGLT2 inhibitors. RESEARCH DESIGN AND METHODS: This was a real-world retrospective cohort study conducted using the Japanese Medical Data Vision database. We identified patients with T2D and treated with SGLT2 inhibitors who were enrolled in the database from April 2014 to October 2019. Cox multivariate regression analyses were performed to determine demographical and clinical factors linked to SGLT2 inhibitor-associated hypoglycemia-related hospitalization. RESULTS: Of 171 622 patients prescribed SGLT2 inhibitors, hypoglycemia-related hospitalization occurred in 216 (0.13%), with 0.60 incidences per 100 person-years. The risk of SGLT2 inhibitor-associated hypoglycemia was higher with each 10-year increase in age (HR 1.49; 95% CI 1.32 to 1.68) and high in patients with body mass index <25 kg/m2 (HR 1.98; 95% CI 1.50 to 2.61), insulin use (HR 3.26; 95% CI 2.43 to 4.38), and sulfonylurea use (HR 1.44; 95% CI 1.02 to 2.03). The risk was lower in women than in men (HR 0.73; 95% CI 0.54 to 0.98) and low in concomitant metformin users (HR 0.52; 95% CI 0.37 to 0.74). CONCLUSIONS: These findings may help minimize the risk of hypoglycemia-related hospitalization due to T2D treatment with SGLT2 inhibitors. We revealed that the risk of hypoglycemia may be higher when combining SGLT2 inhibitors with sulfonylureas and/or insulin. Furthermore, we discovered a high risk of hypoglycemia in older and non-obese patients. These findings may assist in maximizing the benefits of SGLT2 inhibitors for the treatment of T2D.