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High-Dose Versus Standard-Dose Intensity-Modulated Radiotherapy With Concurrent Paclitaxel Plus Carboplatin for Patients With Thoracic Esophageal Squamous Cell Carcinoma: A Randomized, Multicenter, Open-Label, Phase 3 Superiority Trial.
You, J, Zhu, S, Li, J, Li, J, Shen, J, Zhao, Y, Li, X, Jia, L, Li, Q, Yang, J, et al
International journal of radiation oncology, biology, physics. 2023;(5):1129-1137
Abstract
PURPOSE The standard dose (SD) of definitive concurrent chemoradiotherapy (dCRT) remains 50.4 Gy in patients with esophageal cancer; a higher dose, when applied with conventional radiation therapy techniques, increases toxicities without improving survival. We investigated whether a high dose of 59.4 Gy using intensity-modulated radiation therapy (IMRT) would improve survival without increasing toxicities. METHODS Patients with inoperable thoracic esophageal squamous cell carcinoma (SCC) referred for dCRT were randomly assigned (1:1) to high-dose (HD) IMRT (59.4 Gy) or SD IMRT (50.4 Gy). Chemotherapy consisted of 6 cycles of concurrent weekly paclitaxel and carboplatin and a maximum of 2 cycles of consolidation chemotherapy. Nutritional intervention was implemented for patients with malnutrition on the basis of nutritional screening. The primary endpoint was median overall survival (mOS). Analyses were by modified intention to treat. RESULTS Between April 30, 2016, and April 30, 2019, 167 patients were enrolled at 9 participating centers in China. Seventy-one patients in the HD and 73 patients in the SD groups were included in the analysis; 86.8% of the patients completed radiation therapy and 70.1% received 5 or 6 cycles of concurrent chemotherapy. The median follow-up was 36.0 months. The mOS was 28.1 and 26.0 months in the HD and SD arms, respectively (P = .54). A total of 7 treatment-related deaths were observed. Grade 3 or worse treatment-related toxicities were observed in 62% and 68.5% of the patients in the HD and SD arms, respectively (P = .675). CONCLUSIONS For patients with inoperable thoracic esophageal SCC, a dose of 59.4 Gy did not improve survival compared with the SD of dCRT using IMRT.
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Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Benfotiamine in Healthy Subjects.
Sheng, L, Cao, W, Lin, P, Chen, W, Xu, H, Zhong, C, Yuan, F, Chen, H, Li, H, Liu, C, et al
Drug design, development and therapy. 2021;:1101-1110
Abstract
PURPOSE Safety, tolerability and pharmacokinetics of single and multiple ascending doses (SADs/MADs) of benfotiamine were assessed after oral administration in two randomized, double-blind, placebo-controlled, phase I trials. METHODS Healthy subjects were sequentially enrolled into one of five SAD (150-1200 mg) or three MAD (150, 300 or 600 mg) cohorts. In SAD study, each cohort of 12 subjects (n = 10, active; n = 2, placebo) were administrated once-daily doses. In MAD study, each cohort of 16 subjects (n = 12, active; n = 4, placebo) were administrated once-daily on day 1 and twice-daily on day 4-9, followed by a single morning dose on day 10. RESULTS In the SAD study, the median time to reach maximum concentration (Tmax) arrived 1.0 to 2.0 h for thiamine (TM), 3.5 to 8.0 h for thiamine monophosphate (TMP), and 8.0 to 24.0 h for thiamine diphosphate (TDP) after administration of benfotiamine. The area under concentration-time curve from 0 to last measurable concentration (AUC0-t) or maximum observed concentration (Cmax) of TM, TMP, and TDP was less or more dose proportional over the single dose studied except Cmax of TM. Food consumption did not increase the level of TM and TDP at baseline. TM exhibited a relatively long elimination half-life (t1/2) in all doses studied, resulting in accumulation ratio (Rac) of 1.96 to 2.11 and accumulation ratio based on Cmax (Rac, Cmax) of 1.60 to 1.88 following 7 days of multiple dosing. Comparable accumulation results were also obtained for TDP after multiple dosing. The incidence and severity of adverse events (AEs) were similar between benfotiamine and placebo. The commonly reported drug-related AEs were increased ALT and urinary WBC. CONCLUSION Both SAD and MAD studies of benfotiamine in healthy subjects were safe and well tolerated. TM and TDP exhibited moderate accumulation on repeated administration of benfotiamine.
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A Low-Carbohydrate Diet Realizes Medication Withdrawal: A Possible Opportunity for Effective Glycemic Control.
Han, Y, Cheng, B, Guo, Y, Wang, Q, Yang, N, Lin, P
Frontiers in endocrinology. 2021;12:779636
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Many studies have shown that diet restrictions can help glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to look at the efficacy of two diets, the LCD and the low-fat diet (LFD), on glycemic control and clinical treatment. The study was a prospective, open-label, double-arm, randomized controlled trial conducted from March 2019 to December 2020 in China. 134 T2DM participants took part and they were randomly assigned to the LCD group or the low -fat diet (LFD) group. The following were measured at the beginning and end of each intervention: weight, fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), glycosylated haemoglobin (HbA1c), antiglycemic medications, and medications for other diseases and emerging diseases. The effect of decreasing blood glucose control with the LCD is superior to that of the LFD for Chinese patients with T2DM. It also led to a lower medication effects score (MES). It can reduce body weight, BMI, and lipid-lowering agents. Strict diet control and monitoring are the keys to managing diabetes. Further larger scale studies are needed to obtain more evidence.
Abstract
Objective: Multiple studies have confirmed that diet restrictions can effectively realize glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). In 2018, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) stated that individuals can select a low-carbohydrate diet (LCD) according to their needs and preferences. Owing to the influence of Chinese traditional eating habits, only a small portion of patients in China have achieved their blood glucose goals. As a result, the Chinese government will incur huge expenditures. Method: This study recruited 134 T2DM participants and randomly assigned them to the LCD group (n = 67) or the low-fat diet (LFD) group (n = 67). All of the patients had a fixed amount of exercise and were guided by clinicians. After a period of dietary washout, all of the patients received corresponding dietary education according to group. The follow-up time was 6 months. The indicators for anthropometry, glycemic control, and medication application parameters were collected and compared between the two groups. Results: There were 121 participants who finally entered the study. The proportions of calories from three major nutrients the participants consumed met the requirements of LCD and LFD. Compared with baseline, the pre-postdifferences of body weight, BMI, and several other indicators were significant except for dosages of insulin used in the LCD group and MES in the LFD group. After the intervention, body weight, body weight index (BMI), fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), and glycosylated hemoglobin (HbA1c) levels in the LCD group decreased significantly (p < 0.05) compared with the LFD group. The number of patients using lipid-lowering agents was significant higher in the LCD group and lower in the LFD group. However, there was no significant difference between the two groups for antihypertensive, hormone-replacement, and other agents. Conclusions: The LCD diet can decrease body weight, glycemic levels, MES, and lipid-lowering agents more than the LFD diet, thus decreasing cost burden in Chinese patients with T2DM. Strict diet control and monitoring are the keys to managing diabetes.
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Non-technical skills curriculum incorporating simulation-based training improves performance in colonoscopy among novice endoscopists: Randomized controlled trial.
Walsh, CM, Scaffidi, MA, Khan, R, Arora, A, Gimpaya, N, Lin, P, Satchwell, J, Al-Mazroui, A, Zarghom, O, Sharma, S, et al
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2020;(6):940-948
Abstract
BACKGROUND AND AIMS Non-technical skills (NTS), involving cognitive, social and interpersonal skills that complement technical skills, are important for the completion of safe and efficient procedures. We investigated the impact of a simulation-based curriculum with dedicated NTS training on novice endoscopists' performance of clinical colonoscopies. METHODS A single-blinded randomized controlled trial was conducted at a single center. Novice endoscopists were randomized to a control curriculum or a NTS curriculum. The control curriculum involved a didactic session, virtual reality (VR) simulator colonoscopy training, and integrated scenario practice using a VR simulator, a standardized patient, and endoscopy nurse. Feedback and training were provided by experienced endoscopists. The NTS curriculum group received similar training that included a small-group session on NTS, feedback targeting NTS, and access to a self-reflective NTS checklist. The primary outcome was performance during two clinical colonoscopies, assessed using the Joint Advisory Group Direct Observation of Procedural Skills (JAG DOPS) tool. RESULTS Thirty-nine participants completed the study. The NTS group (n = 21) had superior clinical performance during their first (P < 0.001) and second clinical colonoscopies (P < .0.001), compared to the control group (n = 18). The NTS group performed significantly better on the VR simulator (P < 0.05) and in the integrated scenario (P < 0.05). CONCLUSION Our findings demonstrate that dedicated NTS training led to improved performance of clinical colonoscopies among novices.
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Protocol for a randomised trial evaluating the effect of applying gamification to simulation-based endoscopy training.
Scaffidi, MA, Khan, R, Walsh, CM, Pearl, M, Winger, K, Kalaichandran, R, Lin, P, Grover, SC
BMJ open. 2019;(2):e024134
Abstract
BACKGROUND Simulation-based training (SBT) provides a safe environment and effective means to enhance skills development. Simulation-based curricula have been developed for a number of procedures, including gastrointestinal endoscopy. Gamification, which is the application of game-design principles to non-game contexts, is an instructional strategy with potential to enhance learning. No studies have investigated the effects of a comprehensive gamification curriculum on the acquisition of endoscopic skills among novice endoscopists. METHODS AND ANALYSIS Thirty-six novice endoscopists will be randomised to one of two endoscopy SBT curricula: (1) the Conventional Curriculum Group, in which participants will receive 6 hours of one-on-one simulation training augmented with expert feedback and interlaced with 4 hours of small group teaching on the theory of colonoscopy or (2) the Gamified Curriculum Group, in which participants will receive the same curriculum with integration of the following game-design elements: a leaderboard summarising participants' performance, game narrative, achievement badges and rewards for top performance. In line with a progressive learning approach, simulation training for participants will progress from low to high complexity simulators, starting with a bench-top model and then moving to the EndoVR virtual reality simulator. Performance will be assessed at three points: pretraining, immediately post-training and 4-6 weeks after training. Assessments will take place on the simulator at all three time points and transfer of skills will be assessed during two clinical colonoscopies 4-6 weeks post-training. Mixed factorial ANOVAs will be used to determine if there is a performance difference between the two groups during simulated and clinical assessments. ETHICS AND DISSEMINATION Ethical approval was obtained at St. Michael's Hospital. Results of this trial will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER NCT03176251.
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Fecal bile acid concentrations in a subpopulation of the wheat bran fiber colon polyp trial.
Alberts, DS, Einspahr, JG, Earnest, DL, Krutzsch, MF, Lin, P, Hess, LM, Heddens, DK, Roe, DJ, Martínez, ME, Salen, G, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2003;(3):197-200
Abstract
Factors that affect the concentration of secondary bile acids in the aqueous phase of stool may have a greater impact on colon carcinogenesis than those that only modify the total fecal bile acid concentration. This hypothesis was tested using stool samples of a subset of participants enrolled in a Phase III colorectal adenomatous polyp prevention trial, which documented the inability of a 13.5 g/day wheat bran fiber (WBF) supplement to reduce polyp recurrence. Stool was collected from 68 consecutively consented participants who were enrolled in a Phase III clinical trial of WBF for the prevention of adenomatous polyp recurrence. Nineteen (27.9%) of these fecal bile acid substudy participants were on the low fiber (2.0 g/day) intervention group, whereas 49 (72.7%) were on the high fiber (13.5 g/day) intervention group for approximately 3 years. Sixty-four participants had both the aqueous and solid phases of stool samples analyzed for bile acid content. Bile acid concentrations, measured in microg/ml for fecal water and microg/mg for dry feces, were determined for lithochilic, deoxycholic, chenodeoxycholic, cholic, ursodeoxycholic, isodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids. There were no significant differences between the low and high fiber groups concerning mean or median aqueous phase concentrations of lithocholic or deoxycholic bile acids. In contrast, the median concentrations of deoxycholic acid and other secondary bile acids (including lithochilic, isodeoxycholic, ursodeoxycholic, isoursodeoxycholic, ursocholic, 7-ketolithocholic, and 12-ketolithocholic acids) were significantly lower for the high fiber group in the solid-phase stool (P < 0.05). These results document that a high WBF intervention, taken for a median of 2.4 years, does not significantly reduce aqueous-phase concentrations of secondary bile acids in stool, although their concentrations in solid-phase stool were suppressed. Thus, the inability of the high WBF intervention to reduce colorectal adenoma recurrence may be a consequence of its lack of effect on fecal aqueous-phase secondary bile acid concentrations.