Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002–2011 in Japan (JDDM32)

Aims/Introduction

Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP‐4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10‐year period from 2002 to 2011.

Materials and Methods

We carried out a cross‐sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data.

Results

Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono‐ and combination therapy. DPP‐4 inhibitors (DPP‐4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono‐ and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two‐ and 14.8‐fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011.

Conclusions

The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP‐4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level.     

Lumped parameter model for hemodynamic simulation of congenital heart diseases

The recent development of computer technology has made it possible to simulate the hemodynamics of congenital heart diseases on a desktop computer. However, multi-scale modeling of the cardiovascular system based on computed tomographic and magnetic resonance images still requires long simulation times. The lumped parameter model is potentially beneficial for real-time bedside simulation of congenital heart diseases. In this review, we introduce the basics of the lumped parameter model (time-varying elastance chamber model combined with modified Windkessel vasculature model) and illustrate its usage in hemodynamic simulation of congenital heart diseases using examples such as hypoplastic left heart syndrome and Fontan circulation. We also discuss the advantages of the lumped parameter model and the problems for clinical use.     

Impact of MRI-based postimplant dosimetric assessment in prostate brachytherapy using contrast-enhanced T1-weighted images

PurposeTo compare contrast-enhanced T1-weighted (CE-T1WI) magnetic resonance imaging (MRI) with computed tomography (CT) for postimplant dosimetry and seed recognition in prostate brachytherapy.Methods and MaterialsA total of 245 patients who received ¹²⁵I prostate brachytherapy with or without external beam radiotherapy were enrolled. For postimplant analysis, CT and MRI scans were obtained at 1 month after seed implantation. For MRI-based dosimetry, T2-weighted images were fused with the CE-T1WI; the prostate was delineated on the T2-weighted images, and the seed detection was performed manually on the CE-T1WI. In CT-based dosimetry, the seed detection was essentially performed automatically. The dosimetric results obtained by MRI-based and CT-based dosimetry were compared.ResultsThe mean prostate D₉₀ (the minimum dose received by 90% of the prostate volume) estimated by MRI-based and CT-based dosimetry were 113% and 115%, respectively, with no significant difference. The mean prostate V₁₀₀ (the percent volume of the postimplant prostate receiving 100% of the prescribed dose) estimated by MRI-based and CT-based dosimetry were 95.2% and 95.8%, respectively, again with no significant difference. The mean prostate V₁₅₀ (the percent volume of the postimplant prostate receiving 150% of the prescribed dose) estimated by MRI-based and CT-based dosimetry were 52.8% and 57.0%, respectively (p < 0.01). In all of the 35 patients (14%) in whom the MRI-based V₁₅₀ were at least 10% lower than the CT-based results, the seed detection by CT-based dosimetry was overestimated in highly seed-clustered areas or in the areas close to calcifications because of reconstruction artifacts in CT images.ConclusionsMRI-based dosimetry using CE-T1WI appears to be acceptable. Our results suggest that MRI-based dosimetry is a practical method for estimation of the higher dose distribution, especially if seeds are clustered together or when they are close to calcifications.     

Deaths within 12 months after (125)I implantation for brachytherapy of prostate cancer: an investigation of radiation safety issues in Japan (2003-2010)

PurposeThe International Commission on Radiological Protection recommends removing the prostate before cremation if death occurs within 12 months after ¹²⁵I brachytherapy. However, the incidence of death within this time frame has not been robustly investigated in any country. The purpose this study was to investigate the incidence and cause of death and actions taken when death has occurred within 12 months after ¹²⁵I brachytherapy for prostate cancer in Japan.Methods and MaterialsData were extracted from the Japan Radioisotope Association database to investigate the total number of implantation cases, number of early deaths after implantation, cause of death, and postmortem actions between September 2003 and the end of June 2010 in Japan. Early death was defined as occurring within 12 months after ¹²⁵I brachytherapy for prostate cancer.ResultsDuring the study period, 15,427 patients underwent ¹²⁵I brachytherapy and 43 (0.28%) died within 12 months after implantation. For 37 of the 43 patients (86%), the brachytherapy source was retrieved together with the prostate gland at autopsy; however, autopsy could not be performed in six (14%) of the deceased patients. The largest proportion of early deaths was because of cerebrovascular or cardiovascular disease (17/43, 40%), followed by malignant tumor (15/43, 35%), and respiratory disease or infection (7/43, 16%).ConclusionsThe incidence of early deaths within 12 months after ¹²⁵I brachytherapy in Japan was 0.28%. In almost all cases, the brachytherapy sources were removed in the intact prostate before the body was cremated and stored appropriately.     

Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.     

Prompt institution of percutaneous cardiopulmonary support managed perioperative refractory vascular spasm after isolated coronary artery bypass grafting surgery

A 51-year-old Japanese male underwent on-pump coronary artery bypass grafting surgery. After weaning from cardiopulmonary bypass (348 min), sudden bradycardia and hypotension occurred, followed by ventricular fibrillation. Although defibrillation and infusion of catecholamine restored sinus rhythm, transesophageal echocardiography demonstrated severely reduced contraction of both ventricles, and perioperative vascular spasm was suspected. As vascular spasm was refractory to medications, percutaneous cardiopulmonary support (PCPS) system was quickly instituted under cardiac massage. Coronary angiography revealed vascular spasm of not only the native coronary arteries but also the implanted left internal thoracic artery. After 3 days of full hemodynamic assist, PCPS was withdrawn with no obvious abnormalities in regional wall motion by transesophageal echocardiography. The patient was extubated on postoperative day 6 with no impaired brain function. In this case, the immediate diagnosis of refractory vascular spasm by transesophageal echocardiography and full cardiocirculatory assistance by PCPS helped to save the life of the patient.