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A randomized, open-label, parallel, multi-center Phase IV study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high-risk Asian patients with hypercholesterolemia.
Kim, JB, Song, WH, Park, JS, Youn, TJ, Park, YH, Kim, SJ, Ahn, SG, Doh, JH, Cho, YH, Kim, JW
PloS one. 2021;(1):e0245481
Abstract
BACKGROUND Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia. METHODS A 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint. RESULTS LDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk patients) with atorvastatin 20 mg than with 10 mg (40.3% vs. 25.6%, p < 0.05). Apolipoprotein B decreased significantly with atorvastatin 20mg versus 10 mg (-36.2% vs. -29.9%, p < 0.05). Lipid ratios also showed greater improvement with atorvastatin 20 mg than with 10 mg (total cholesterol/high-density lipoprotein cholesterol ratio, -33.3% vs. -29.4%, p < 0.05; apolipoprotein B/apolipoprotein A1 ratio, -36.7% vs. -31.4%, p < 0.05). Atorvastatin 20 mg was more cost-effective than atorvastatin 10 mg in terms of both the average and incremental cost-effectiveness ratios. Safety and tolerability of atorvastatin 20 mg were comparable to those of atorvastatin 10 mg. CONCLUSION In high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg.
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Effect of high-fat diet on the pharmacokinetics and safety of flumatinib in healthy Chinese subjects.
Kuang, Y, Song, HL, Yang, GP, Pei, Q, Yang, XY, Ye, L, Yang, S, Wu, ST, Guo, C, He, QN, et al
Cancer chemotherapy and pharmacology. 2020;(3):339-346
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Abstract
PURPOSE To evaluate the effect of a high-fat diet on the pharmacokinetics and safety of flumatinib mesylate tablets in healthy Chinese subjects. METHODS This study was a randomized, open-label, single-dose, two-period crossover trial in which subjects were randomly assigned to take 400 mg of flumatinib mesylate after a high-fat diet or a fasted state. After a 14-day washout period, the two groups were administered flumatinib mesylate under opposite conditions. Blood samples were collected at baseline 0 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, and 96 h, respectively. Plasma concentrations of flumatinib and its metabolites (M1 and M3) were analyzed using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated using the non-compartmental module of the Phoenix WinNonlin Version 7.0 software. BE module of WinNonLin was used for statistical analysis of AUC0-t, AUC0-∞ and Cmax in plasma. RESULTS Twelve healthy subjects, half male and half female, were enrolled. One subject withdrew due to a treatment-emergent adverse event. Eleven subjects were administered drugs on fasting and 12 were administered drugs after a high-fat diet. On high-fat diet/fasting, the least square geometric mean (LSGM) ratios of flumatinib, M1, M3, and their 90% confidence interval (CI) were as follows: for flumatinib, Cmax, AUC0-t and AUC0-∞ were 281.65% (225.80-351.31%), 167.43% (143.92-194.79%), and 166.87% (143.47-194.09%); for M1, Cmax, AUC0-t, and AUC0-∞ were 188.59% (145.29-244.79), 163.94% (149.11-180.24%), and 164.48% (150.36-179.94%); for M3, Cmax, AUC0-t, and AUC0-∞ were 63.47% (54.02-74.57%), 85.23% (74.72-97.22%), and 96.73% (86.63-108.02%). CONCLUSION Among the subjects, oral administration of 400 mg of flumatinib was safe and well tolerated. High-fat diet significantly increases the exposure to flumatinib, therefore, fasting may be recommended. CLINICAL TRIAL REGISTRATION The study was registered at chictr.org Identifier: ChiCTR-IIR-17013179.
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Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.
Guo, C, Kuang, Y, Zhou, H, Yuan, H, Pei, Q, Li, J, Jiang, W, Ng, CM, Chen, X, Huo, Y, et al
Circulation. Genomic and precision medicine. 2020;(4):e002602
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Abstract
BACKGROUND Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.
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The impact on glycemic control through progressive resistance training with bioDensityTM in Chinese elderly patients with type 2 diabetes: The PReTTy2 (Progressive Resistance Training in Type 2 Diabetes) Trial.
Hangping, Z, Xiaona, Q, Qi, Z, Qingchun, L, Na, Y, Lijin, J, Siying, L, Shuo, Z, Xiaoming, Z, Xiaoxia, L, et al
Diabetes research and clinical practice. 2019;:64-71
Abstract
AIMS: To evaluate the effects of a novel, low-volume, high-intensity Progressive Resistance Training (PRT) technique on blood glucose control in elderly Chinese patients with Type 2 Diabetes. MATERIALS AND METHODS The PReTTy2 trial enrolled 300 male and female patients with Type 2 Diabetes in a randomized resistance training program with the bioDensity™ technique. 100 were control patients with no training intervention and 200 had resistance training. Anthropometry, biochemical parameters, HbA1c and fasting plasma glucose (FPG) were measured at baseline, 3-month and 6-month intervals. RESULTS 265 patients completed the study with no adverse events. There were no statistically significant differences in HbA1c for all patients, control and PRT groups, at baseline (p = 0.60), 3 months (p = 0.42) and 6-months (p = 0.45). Subgroup analysis with baseline HbA1c > 7.5% (58 mmol/mol), showed statistically significant differences in HbA1c and FPG between groups at 6 months (p < 0.05). All PRT group patients had statistically significant differences from baseline at 6 months for HDL (1.25 + 0.32 vs. 1.17 + 0.26 mmol/L, p < 0.001), LDL (3.23 ± 0.89 vs. 2.93 ± 0.80 mmol/L, p < 0.001) and total cholesterol (4.97 ± 1.22 vs. 4.58 ± 1.03 mmol/L, p < 0.001). CONCLUSIONS PRT improves glycemic indices in elderly patients with Type 2 Diabetes with poor glucose control as an adjunct to diet and medication. Progressive Resistance Training with bioDensity™ is feasible, safe and effective in elderly patients with Type 2 Diabetes.
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Dynamics of attentional bias for food in Dutch and Chinese children and the role of executive control.
Liu, Y, Nederkoorn, C, Roefs, A
Appetite. 2019;:104421
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Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section✰.
Ma, JH, Wang, SY, Yu, HY, Li, DY, Luo, SC, Zheng, SS, Wan, LF, Duan, KM
Psychiatry research. 2019;:252-258
Abstract
This study aimed to explore the effect of prophylactic ketamine administration on postpartum depression in Chinese woman undergoing cesarean section. This randomized controlled study included 654 Chinese women undergoing cesarean section. At 10 min after child birth, patients in the ketamine group were given 0.5 mg/kg ketamine, whereas patients in the control group received standard postpartum care. At the end of operation, all patients were armed with a patient-controlled intravenous analgesia device. The primary outcome was the prevalence of postpartum depression (PPD), as assessed by the Edinburgh Postnatal Depression Scale (EPDS), and the secondary outcomes included the safety assessment and the Numerical Rating Scale (NRS) of postoperative pain. The prevalence of postpartum blues and postpartum depression were significantly lower in the ketamine group than in the control group. Logistic analysis showed that ketamine administration protected against postpartum depression, and PPD-associated risk factors included stress during pregnancy, antenatal depressive symptom and antenatal suicidal ideation. In addition, the antidepressive effect of prophylactic ketamine was stronger in mothers with a history of moderate stress during pregnancy, antenatal depressive symptom and antenatal suicidal ideation. Our findings suggest that ketamine functions as a prophylactic agent against PPD.
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The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia.
Shinta, D, , , Adhiyanto, C, Htet, MK, Fahmida, U
Nutrients. 2019;(4)
Abstract
Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6-17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 μg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6.
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Study Protocol for a Prospective, Multicenter, Randomized, Open-Label, Parallel-Group Clinical Trial Comparing the Efficacy and Safety of a Needle-Free Insulin Injector and a Conventional Insulin Pen in Controlling Blood Glucose Concentrations in Chinese Patients with Type 2 Diabetes Mellitus (The FREE Study).
Ji, L, Chen, L, Wang, Y, Ma, Z, Ran, X, Sun, Z, Xu, X, Wang, G, Guo, L, Shan, Z
Advances in therapy. 2019;(6):1485-1496
Abstract
INTRODUCTION China has the largest number of diabetic patients in the world. In the past 2 decades, the prevalence of diabetes in China has increased dramatically, and the current status of diabetes control in the diabetic population is not satisfactory. Although insulin is currently recognized in diabetes treatment guidelines as the therapeutic option for patients not adequately controlled by diet/exercise and oral agents, the proportion of patients with type 2 diabetes using insulin is still very low, and the time when insulin therapy is initiated is relatively late. In using insulin injections, concerns about the complexity of the treatment regimen, a fear of needles, and other psychological barriers can affect insulin treatment, impacting on patient compliance and potentially resulting in a poor treatment response. Another type of insulin injection device that has become available recently, the needle-free injector, is now being used in clinical practice because of its unique features and patients' injection experiences. The aims of this study are to investigate the efficacy and safety of the needle-free injector-based insulin treatment in blood glucose control in patients with type 2 diabetes, as compared with a conventional needle-based insulin treatment, and to evaluate patient satisfaction with the different insulin delivery methods. METHODS AND PLANNED OUTCOMES A prospective, multicenter, randomized, open-label, parallel-group clinical trial was designed and implemented in China. A total of 420 patients with type 2 diabetes from ten research centers will be enrolled in the study. The primary efficacy endpoint is the change in the glycosylated hemoglobin (HbA1c) level from baseline to after 16 weeks of treatment after randomization. Secondary efficacy endpoints include measurements of blood glucose concentrations, the rate of achieving the target HbA1c level of less than 7%, patients' quality-of-life (as determined by the SF-36 questionnaire), the insulin dose administered, compliance with insulin therapy, and patients' satisfaction with their injection device. ETHICS AND DISSEMINATION The study was approved by the Independent Ethics Committee (IEC) of Peking University Peoples Hospital and was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent will be obtained from all participants before any study-related procedures are implemented. It is hoped that the study will provide evidence for the clinical application of the needle-free injector by providing data on its efficacy and safety, as compared with a conventional insulin pen, in the Chinese type 2 diabetes population. When available, the results will be published in an international peer-reviewed journal. TRIAL REGISTRATION ClinicalTrials.gov Identifier, NCT03243903. Registration date, August 9, 2017. FUNDING Beijing QS Medical Technology Co., Ltd.
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The Association of Acylcarnitines and Amino Acids With Age in Dutch and South-Asian Surinamese Living in Amsterdam.
Muilwijk, M, Vaz, FM, Celis-Morales, C, Peters, RJG, van Valkengoed, IGM
The Journal of clinical endocrinology and metabolism. 2018;(10):3783-3791
Abstract
CONTEXT Type 2 diabetes and cardiovascular disease occur more frequently and at a younger age in South-Asians than Europeans. This may be related to differences in regulation of the fatty acid metabolism during aging. We compared age-related acylcarnitine and amino acid concentrations in Dutch and South-Asian Surinamese study participants. METHODS We measured types of acylcarnitine and amino acid concentrations in plasma (by tandem mass spectrometry) in a random subsample of 350 Dutch and 350 South-Asian Surinamese origin participants of the Healthy Life in an Urban Setting study (Amsterdam, Netherlands). We derived principal components (PCs) from the metabolites. Linear regression was used to assess differences in PCs and individual metabolite concentrations, and their age trends between the groups by sex. We adjusted for body mass index and intake of fat and total energy. RESULTS Mean age was 44.8 (SD, 13.3) years. Amino acid concentrations were higher among South-Asian Surinamese women compared with Dutch women; acylcarnitine and amino acid levels were higher among South-Asian Surinamese men than Dutch men. Metabolite levels increased similarly with age in both ethnic groups. Results remained similar after adjustment. CONCLUSION Ethnic differences in metabolite concentrations suggest that fatty acid and amino acid metabolism are more dysregulated among South-Asian Surinamese compared with Dutch from a young age. During adulthood, metabolites increase similarly in both ethnic groups.
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Genome-wide DNA Copy-number Analysis in ACTS-CC Trial of Adjuvant Chemotherapy for Stage III Colonic Cancer.
Ishikawa, T, Uetake, H, Murotani, K, Kobunai, T, Ishiguro, M, Matsui, S, Sugihara, K
Anticancer research. 2016;(3):853-60
Abstract
BACKGROUND The adjuvant chemotherapy trial of TS-1 for colon cancer phase III trial was designed to validate the non-inferiority of the oral fluoropyrimidine S-1 to uracil and tegafur/leucovorin as adjuvant chemotherapy for stage III colonic cancer. As a prospective biomarker study of this trial, DNA copy number was studied using formalin-fixed, paraffin-embedded specimens. MATERIALS AND METHODS FFPE blocks were obtained from 795 patients of the 1,535 patients enrolled in the study. The quality of extracted DNA was assessed using arbitrarily primed polymerase chain reaction and microfluidic analysis. Genomic copy-number alterations in cancer were analyzed by high-density single-nucleotide polymorphism arrays. Copy-number changes in Japanese patients with colonic cancer were compared with those in Western countries using data from a previously reported meta-analysis. We then compared genome-wide segment copy number and clinicopathological features of colorectal cancer. RESULTS Genome-wide copy number was analyzed in 161 samples and DNA copy-number alteration profiles showed frequent DNA copy-number gains at chromosome 7, 8q and 13, and losses at 4, 5q, 8p, 17p and 18q. The weighted kappa statistic from comparing copy-number alteration status with data from Western countries was 0.828 (95% confidence interval=0.786 -0.871). DNA copy-number alterations of 8,684 segments were compared with clinicopathological features in 161 patients. Location of the tumor correlated with genomic segments of chromosome 4, 5, 7, 8, 13, 14, 18 and 20. Differentiation of the tumor correlated with segments in chromosome 4, 6, 8, 11, 13, 14,15, 16, 17 and 20. CONCLUSION Somatic copy-number alteration profiles of stage III colonic cancer in the Japanese ACTS-CC trial closely agreed with the results of previous Western studies. Location and differentiation of the tumor correlated with DNA copy-number alterations. Our findings will facilitate understanding the characteristics of colonic cancer. Further investigation may contribute to the exploration of valid biomarkers.