Factor affecting severe atherothrombotic cerebral infarction in patients with type 2 diabetes mellitus: Large-scale claim database analysis of Japan.

Aims: This study aimed to investigate the factors associated with the exacerbation of the severity of atherothrombotic brain infarction at discharge in patients with type 2 diabetes using a large-scale claims database.

Materials And Methods: This retrospective cross-sectional study utilized the Medical Data Vision administrative claims database, a nationwide database in Japan using acute care hospital data, and the Diagnosis Procedure Combination system. Diagnosis Procedure Combination data collected between April 1, 2008, and December 31, 2022, were extracted.

Real-world risk of cardiovascular diseases in patients with type 2 diabetes associated with sodium-glucose cotransporter 2 inhibitors in comparison with metformin: A propensity score-matched model analysis in Japan.

We aimed to compare the effects of cardiovascular disease risk in Japanese patients with type 2 diabetes on sodium-glucose cotransporter 2 inhibitors (SGLT2Is) or metformin. This retrospective, real-world cohort study was carried out using a claims database and propensity score matching; 58,402 eligible patients (29,201 per group) were included. The outcomes included nonfatal myocardial infarction, angina pectoris, nonfatal stroke, hospitalization for heart failure and composite end-points.

A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales.

Background: Anticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales.

Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations.

Background: Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown.

Methods: Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients.

Results: Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs.

[Association between Elimination Half-life of Benzodiazepines and Falls in the Elderly: A Meta-analysis of Observational Studies].

Benzodiazepine receptor agonists (BZDRAs) have been associated with an increased risk of falls in the elderly. However, the association between the elimination half-life (t) of BZDRAs and the difference between benzodiazepines (BZDs) and non-benzodiazepines (Z-drugs) has not been clarified. By conducting a meta-analysis of observational studies, we compared the risk of falls with respect to 1) short-acting BZDRAs (t<12 h) vs.

Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies.

Background: Human papillomavirus (HPV) vaccines have been shown to be effective for the eradication of HPV and prevention of cervical cancer. However, the number of women who receive HPV vaccinations has decreased over the last several years in Japan, due to concerns about adverse reactions associated with the vaccines. We evaluated the safety of three types of HPV vaccines separately in young women and the difference in the risk of adverse reactions between HPV and other vaccines by conducting a meta-analysis.

Predictors of the therapeutic effect of sivelestat in patients with acute lung injury associated with systemic inflammatory response syndrome.

Background: Sivelestat, a neutrophil elastase inhibitor, was previously approved in Japan for the treatment of acute lung injury associated with systemic inflammatory response syndrome. However, sivelestat produced inconsistent therapeutic benefits. This study aimed to identify factors predicting the therapeutic effects of sivelestat.

Determinants of the over-anticoagulation response during warfarin initiation therapy in Asian patients based on population pharmacokinetic-pharmacodynamic analyses.

Unlabelled: To clarify pharmacokinetic-pharmacodynamic (PK-PD) factors associated with the over-anticoagulation response in Asians during warfarin induction therapy, population PK-PD analyses were conducted in an attempt to predict the time-courses of the plasma S-warfarin concentration, Cp(S), and coagulation and anti-coagulation (INR) responses. In 99 Chinese patients we analyzed the relationships between dose and Cp(S) to estimate the clearance of S-warfarin, CL(S), and that between Cp(S) and the normal prothrombin concentration (NPT) as a coagulation marker for estimation of IC50. We also analyzed the non-linear relationship between NPT inhibition and the increase in INR to derive the non-linear index λ.

Inter-individual differences in baseline coagulation activities and their implications for international normalized ratio control during warfarin initiation therapy.

Background And Objective: Genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) and patient demographic characteristics are responsible for inter-individual differences in warfarin maintenance dosage requirements. At present, however, the factors associated with over-anticoagulation responses, especially before achieving the maintenance phase, have not been completely clarified. In this study, we investigated the effects of baseline coagulation activity assessed in terms of the level of fully carboxylated plasma normal prothrombin (NPT) on international normalized ratio (INR) control during the induction phase of warfarin therapy.

Computer-based evolutionary search for a nonlinear conversion function for establishing in vitro-in vivo correlation (IVIVC) of oral drug formulations.

Establishment of in vitro-in vivo correlation (IVIVC) accelerates optimization of desirable drug formulations and/or modification of the manufacturing processes in the scale-up and post-approval periods. This article presents a method of finding the optimal conversion function for establishing Level A point-to-point IVIVC, based on a computer-based evolutionary search technique. Gene expression programming (GEP) is a technique for optimizing a mathematical expression tree with the help of a genetic algorithm.

Population pharmacokinetics of R- and S-carvedilol in Japanese patients with chronic heart failure.

Carvedilol is a beta-adrenoceptor antagonist used for treating chronic heart failure (CHF). Two clinical studies were conducted to evaluate the population pharmacokinetics and pharmacodynamics of R- and S-carvedilol, and associated covariates, in patients with CHF. Fifty-eight patients (male=45, female=13) with New York Heart Association class I-IV CHF were enrolled in two clinical studies.

A study of cardiovascular function in Tsumura Suzuki obese diabetes, a new model mouse of type 2 diabetes.

Diabetes mellitus is a well known and important risk factor for cardiovascular diseases, including heart failure. A new model of Type 2 diabetes, Tsumura Suzuki Obese Diabetes (TSOD) mice, was introduced recently into the research field of diabetes. The cardiac functions of TSOD mice were studied in comparison with Tsumura Suzuki Non Obesity (TSNO, non-diabetic control) mice, for the first time.

Stereoselective first-pass metabolism of verapamil in the small intestine and liver in rats.

Verapamil (VP) is used as a racemate but shows stereoselective pharmacokinetics and pharmacodynamics. It undergoes extensive first-pass metabolism. Stereoselective first-pass metabolism in the intestine and liver was investigated in vivo and in vitro to determine its impact on the disposition of VP and its main metabolite, norverapamil (NVP).

Enantioselective and highly sensitive determination of carvedilol in human plasma and whole blood after administration of the racemate using normal-phase high-performance liquid chromatography.

A highly sensitive HPLC method for enantioselective determination of carvedilol in human whole blood and plasma was developed. Carvedilol and S-carazolol as an internal standard extracted from whole blood or plasma were separated using an enantioselective separation column (Chiralpak AD column; 2.0 diameter x 250 mm) without any chiral derivatizations.

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters.

Evaluation of Bayesian estimation of pharmacokinetic parameters.

The validity of pharmacokinetic parameters estimated by the maximum a posteriori probability (MAP) Bayesian method was investigated by simulation studies. A 1-compartment model with bolus intravenous administration was used as a pharmacokinetic model, and the coefficients of variation for the parameters and residual error were set at 30% and 10%, respectively. The accuracy of the posterior modes of pharmacokinetic parameters estimated by the MAP Bayesian method was assessed by the difference between the true value and the estimated value.

[Effectiveness of anti-emetics for the prophylaxis of cisplatin-induced delayed emesis: a systematic review].

We performed a systematic review of the effectiveness of anti-emetics for prophylaxis of cisplatin-induced delayed emesis using meta-analysis. We selected 12 reports of randomized controlled trials from MEDLINE (1966-2003. 4) and The Cochrane Library Issue 1, 2003.

Pharmacokinetics and preventive effects of targeted catalase derivatives on hydrogen peroxide-induced injury in perfused rat liver.

Purpose: To investigate the pharmacokinetics and preventive effects of liver-targeted catalase (CAT) derivatives on hepatic injury caused by reactive oxygen species.

Methods: The hepatic uptake of 111In-CAT, galactosylated (Gal-), mannosylated (Man-) and succinylated (Suc-) CAT was investigated in isolated perfused rat livers in a single-pass constant infusion mode. Then, pharmacokinetic parameters were obtained by fitting equations derived from a one-organ pharmacokinetic model to the outflow profile.