Objective: In the previous study, the CYP database was constructed in order to relate drug-drug interactions to the CYP metabolic information of the package inserts.  In this study, we evaluated the clinical usefulness of the CYP database by using the Pharmaceutical and Medical Devices Agency (PMDA) Drug Monitoring Information.
Methods: We examined the drugs in CYP isoform responsible for drug metabolism.  The age, sex, suspect drugs and co-administered drugs were extracted from 6,236 cases of the PMDA database of drug monitoring from January till November of 2008.
Results: Twenty-three percent of all cases had co-administered drugs.  Forty-five percent of these cases were metabolized both suspect and co-administered drugs by the same CYP isoform, and three fourths of these cases were able to be detected only by the CYP database.  In addition, the administration of substrate medicines in combination with substrate medicines was the largest (57%), followed by cases of substrate medicines in combination with inhibitor medicines (28%).  Seventy-seven percent of the suspect drugs that had a large number of reported cases of side effects were substrate medicines, and the frequency of co-administration with substrate medicines was very high.
Conclusion: These data suggest that the CYP database, being used together with package inserts, might be a clinically useful tool to avoid adverse events caused by drug-drug interactions.

BACKGROUND: Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects. METHODS: We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (Deltainsulin/Deltaglucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance). RESULTS: In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles. CONCLUSION: These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status.
Asian Continental Ancestry Group ; Cholesterol, HDL* ; Fasting ; Glucose ; Glucose Tolerance Test ; Hand ; Humans ; Insulin* ; Linear Models ; Triglycerides*

Lower-extremity antigravity muscle contraction (the static muscle pump and muscle mechanoreflex) and the baroreflex are involved in regulating blood pressure (BP) during upright standing. We hypothesized that in females with orthostatic hypotension (showing a decrease > 20/10 mmHg within 3 min upon standing from supine), the muscle pump and mechanoreflex of the antigravity muscles is small during upright standing in those who have not undergone exercise training. To test this hypothesis, we compared the cardiovascular responses to head-up tilt, head-up suspension, head-up tilt + venous occlusion (which stops venous return from the lower extremities by static muscle pump), and head-up suspension + venous occlusion of 14 young females with orthostatic hypotension, of which seven had undergone exercise training (tOH) and seven had not (uOH), with those of eight females with orthostatic normotension (control) who had not undergone exercise training. Changes in BP, heart rate (HR), and stroke volume (SV) during both head-up tilt and suspension were measured. Although the increase in HR was larger and the decrease in SV tended to be smaller during head-up tilt than during suspension in the tOH, the response patterns of both were the same in the uOH. In occlusion trials, the increase in HR was larger during head-up tilt than during suspension in the tOH, whereas the increases in HR in both scenarios were the same in the uOH. These findings suggest a small muscle mechanoreflex of the antigravity muscles during upright standing in females with orthostatic hypotension who have not undergone exercise training.

Retrospective cohort study.

Background: Although practicing advanced care planning (ACP) has recently been recommended, little is known about physicians’ practice of ACP, and barriers to ACP in Japan. We aimed to clarify the proportion of physicians practicing ACP and explore barriers to ACP. Methods: We conducted a cross-sectional survey among physicians at a tertiary hospital (934 beds) in 2019, and asked them about their practice and awareness of ACP as well as beliefs regarding end-of-life discussions. A multivariate logistic regression analysis was conducted to explore barriers to their practice of ACP. Results: In total, 90 of 186 physicians responded (response rate, 48%). Forty-two (46%; 95% confidence interval=37-57%) reported that they practiced ACP. In multivariate analysis, determinants of “not” practicing ACP included the lack of awareness of ACP and physicians’ greater beliefs regarding the lack of resources as well as the lack of time and perception of burden. Conclusion: Even at the tertiary hospital, only less than a half of physicians practiced ACP, and the lack of their awareness of ACP and various beliefs served as barriers to their practice. Initiatives to raise awareness of ACP and optimize the management to ensure sufficient time and resources for physicians may be promising to promote ACP.

Retrospective cohort study.

Objective: To evaluate the efficacy of high-flow nasal cannula oxygen (HFNC) for dyspnea in patients with advanced disease. Methods: A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Ichu-shi Web. Inclusion criteria were: 1) randomized controlled trials evaluating the effect of HFNC on dyspnea; 2) aged 18 years or older with advanced disease with hypoxemia; 3) control group was conventional oxygen therapy or noninvasive positive pressure ventilation. Exclusion criteria were: 1) patients in intensive care unit, 2) weaning from ventilator. Results: Six studies (4 from database searches, and 2 from hand searches) were included. In the 2 studies evaluating short-term intervention, one showed HFNC was more efficacious, and the other conventional oxygen was more efficacious. In the 2 studies evaluating long-term interventions: one showed HFNC was more efficacious, and the other showed no significant difference. In the 2 studies evaluating the intervention during exercise, one showed HFNC was more efficacious, and the other showed no significant difference. Conclusion: HFNC may be effective for dyspnea in patients with advanced disease associated with hypoxemia.