Rapid response to a coronavirus disease 2019 (COVID-19) outbreak in a psychiatry hospital-Kanazawa City, Japan, March to April 2020.

A coronavirus disease 2019 (COVID-19) outbreak in a psychiatry hospital revealed specific challenges in its response such as difficulty in isolation, transfer, and identification of close contacts, suboptimal infection control practices, and shortage of personal protective equipment, which were overcome by support from the public health center and a neighboring university hospital.

[Retrospective Examination of Usefulness and Adverse Effects of Tapentadol in Patients with Cancer Pain during Anticancer Treatment].

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

[A New Twist on the Administration of Naldemedine for Opioid-Induced Constipation in an Outpatient].

Opioid-induced constipation(OIC)occurs with high frequency in patients with cancer undergoing pain treatment using opioids. Osmotic or irritant laxatives are usually used to prevent OIC. Recently, naldemedine has become operational for OIC. Although naldemedine achieved the desired effect, diarrhea is a little feared from the results of clinical phase III study(V9236 clinical trial). We herein report the use of naldemedine to alleviate diarrhea and expect the improvement of the quality of the bowel habits in outpatients with cancer undergoing pain treatment using opioids.

[Combinatorial Use of Rapid-Onset Opioid and Short-Acting Opioid Is Effective against Breakthrough Cancer Pain].

Breakthrough cancer pain is divided into "predictable breakthrough pain" and "unpredictable breakthrough pain". Uncontrolled breakthrough pain in cancer negatively affects the quality of life of the patients. The short-acting opioid(SAO) requires considerable time to produce analgesia, and is not adequate as a rescue drug. The rapid-onset opioid(ROO)immediately produces analgesia, but its appropriate usage is difficult. For instance, the frequency and interval of ROO usage is limited, making the optimization of dosage cumbersome. Therefore, ROO has not yet gained popularity. Here, we report that a combinatorial use of ROO and SAO is effective against breakthrough cancer pain, with SAO and ROO being suitable for "predictable breakthrough pain", and "unpredictable breakthrough pain", respectively. The effectiveness and safety of this combination were assessed for many patients with breakthrough cancer pain.

Single administration of vildagliptin attenuates postprandial hypertriglyceridemia and endothelial dysfunction in normoglycemic individuals.

Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.

Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals - a randomized cross-over trial.

BACKGROUND: Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. METHODS: Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. RESULTS: Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. CONCLUSION: Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state.

Add-on ezetimibe reduces small dense low-density lipoprotein cholesterol levels without affecting absorption of eicosapentaenoic acid in patients with coronary artery disease: a pilot study.

BACKGROUND: Residual risk of cardiovascular disease from increased small dense low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this study was to evaluate the effect of ezetimibe as an add-on to statins and supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of EPA in patients with coronary artery disease. METHODS: The study population consisted of ten male patients who were concurrently receiving statins and EPA 1,800 mg/day. Serum lipids and PUFAs, including EPA and arachidonic acid, were measured in blood samples collected before ezetimibe (baseline), 4 weeks after starting 10-mg/day ezetimibe, and 4 weeks after discontinuing ezetimibe. RESULTS: Ezetimibe significantly decreased sdLDL-cholesterol levels after 4 weeks of treatment (baseline 35 ± 13 mg/dl; treatment 27 ± 9 mg/dl), but the levels returned to baseline after discontinuation of ezetimibe (37 ± 13 mg/dl). The concentration of EPA did not significantly change during the study. CONCLUSION: Ezetimibe shows great promise as an add-on therapy to statins to reduce sdLDL-cholesterol-related residual risk of cardiovascular disease without affecting absorption of supplemental EPA in patients with coronary artery disease.

Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects.

BACKGROUND: No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans. METHODS AND RESULTS: In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10). CONCLUSIONS: In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

Bezafibrate improves postprandial hypertriglyceridemia and associated endothelial dysfunction in patients with metabolic syndrome: a randomized crossover study.

BACKGROUND: Postprandial elevation of triglyceride-rich lipoproteins impairs endothelial function, which can initiate atherosclerosis. We investigated the effects of bezafibrate on postprandial endothelial dysfunction and lipid profiles in patients with metabolic syndrome. METHODS: Ten patients with metabolic syndrome were treated with 400 mg/day bezafibrate or untreated for 4 weeks in a randomized crossover study. Brachial artery flow-mediated dilation (FMD) and lipid profiles were assessed during fasting and after consumption of a standardized snack. Serum triglyceride and cholesterol contents of lipoprotein fractions were analyzed by high-performance liquid chromatography. RESULTS: Postprandial FMD decreased significantly and reached its lowest value 4 h after the cookie test in both the bezafibrate and control groups, but the relative change in FMD from baseline to minimum in the bezafibrate group was significantly smaller than that in the control group (-29.0 ± 5.9 vs. -42.9 ± 6.2%, p = 0.04). Bezafibrate significantly suppressed postprandial elevation of triglyceride (incremental area under the curve (AUC): 544 ± 65 vs. 1158 ± 283 mg h/dl, p = 0.02) and remnant lipoprotein cholesterol (incremental AUC: 27.9 ± 3.5 vs. 72.3 ± 14.1 mg h/dl, p < 0.01). High-performance liquid chromatography analysis revealed that postprandial triglyceride content of the chylomicron and very low-density lipoprotein fractions was significantly lower in the bezafibrate group than in the control group (p < 0.05). CONCLUSION: Bezafibrate significantly decreased postprandial endothelial dysfunction, and elevations of both exogenous and endogenous triglycerides in patients with metabolic syndrome, suggesting that bezafibrate may have vascular protective effects in these patients. CLINICAL TRIAL REGISTRATION: Unique Identifiers: UMIN000012557.

Arterial stiffness determined according to the cardio-ankle vascular index is associated with paroxysmal atrial fibrillation: a cross-sectional study.

BACKGROUND: Several lines of evidence suggest that atrial fibrillation (AF) may be a consequence of vascular disease. We investigated the relationship between cardio-ankle vascular index (CAVI), a new index of arterial stiffness, and the presence of paroxysmal AF (PAF). METHODS AND RESULTS: 181 outpatients (91 patients with PAF and 90 age- and gender-matched subjects without PAF) were analysed for their sinus rhythm. The CAVI was significantly higher in patients with PAF than in subjects without PAF (9.0±1.0 vs 8.7±0.8, p<0.01). In all subjects, the CAVI was significantly correlated with the left ventricular mass index (r=0.30, p<0.01), left atrial diameter (r=0.22, p<0.01), and augmentation index, a parameter of wave reflection (r=0.32, p<0.01), in addition to age, systolic blood pressure and pulse pressure. Logistic analysis demonstrated that the CAVI was independently associated with PAF even after adjustment for confounding factors. The adjusted OR of PAF was 1.8 for each unit increase in the CAVI (p=0.01). CONCLUSIONS: Our finding suggests that increased arterial stiffness may be involved in the maintenance of AF.

Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non-diabetic subjects: a preliminary report.

BACKGROUND: Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile. METHODS: A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test. RESULTS: Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 µg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from -4.2 ± 0.5% to -2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = -0.46, p = 0.03) and RLP-C (r = -0.45, p = 0.04). CONCLUSION: Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.