Patient Preferences for Benefits,Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes

Introduction/BackgroundTherapy with infused or injected hypomethylating agents (HMAs) may lead to higher treatment administration burden (ie, local reaction, visit frequency and duration) vs. oral HMAs. ObjectivesTo reveal preferences of US and Canadian patients with myelodysplastic syndromes (MDS) for HMAs’ benefits, risks, and administration burden through an online discrete-choice experiment (DCE).Materials and MethodsChoice of DCE attributes and survey development were informed by literature review and interviews with clinicians, MDS patients, and caregivers serving as patient proxies, and patient advocacy groups (PAGs) representatives, including from AAMAC, AAMDS, and MDSF. DCE choice tasks were analyzed using random parameter logit models. Survey patients were recruited by the PAGs via their networks. To understand key preference drivers and how much patients were willing to trade between attributes, we calculated each attribute's relative attribute importance (RAI) and marginal rates of substitution.ResultsOne hundred eighty-four respondents (including 158 patients; mean age, 67.2 years; male, 50.5%; White, 50.5%; US residents, 88%) completed the survey. MDS risk was low (34.8%), high (30.9%), or unknown (34.2%). RAI (in decreasing order) was as follows: risk of AML (40%), fatigue level (33%), number of visits (12%), mode of administration (6%), visit duration (5%), and administration frequency (4%). Assuming the same risk of AML transformation or level of fatigue, most respondents (76.6%) were predicted to switch to an oral pill if it were available to them.ConclusionGiven equivalent effectiveness across HMAs, patients’ preferences for HMA administration method should be considered in treatment decision-making to minimize burden and facilitate adherence.     

Gelatin-based hemostatic agents for medical and dental application at a glance: A narrative literature review

Uncontrolled bleeding is linked to higher treatment costs, risk of post-surgical infection and increased disease and death. Hemostatic agents are used to treat excessive bleeding. A good hemostatic agent controls bleeding effectively, reduces the need for blood transfusion, removes the need for systemic drugs to control bleeding, results in shorter surgery time, and reduces the cost and length of hospital stay of the patient. Gelatin-based hemostatic agents have been widely used in medical and dental procedures, owing to their biodegradability and biocompatibility, as well as availability and low cost of raw materials. In this narrative literature review, we discuss the background and different types of gelatin-based hemostatic agents in medical and dental procedures, the comparison of gelatin-based and non-gelatin-based hemostatic agents, and the usage and development of enhanced or novel gelatin-based hemostatic agents. Gelatin-based hemostatic agents are effective and important part of bleeding control, as evidenced by its wide application in medicine and dentistry. The development of novel combination gelatin-based hemostatic agents has much potential for effective control of excessive bleeding.     

Evaluation of the effectiveness of bioactive glass fillers against Candida albicans adhesion to PMMA denture base materials: An in vitro study

BackgroundDentures with antimicrobial properties are desirable for preventing Candida albicans adhesion. This study was to assess the effectiveness of bioactive glass (BAG) on C. albicans adhesion, surface roughness, and hardness of denture base materials.MethodsHeat-polymerized (HP) and autopolymerized (AP) acrylic resins were used to fabricate 240 disk specimens (120/material, 60/C. albicans, 60/surface roughness and hardness). Specimens were divided into five groups (n = 10) based on the BAG concentration: 0.5, 1.5, 3, 5, and 7.5 wt% of the acrylic powder, with a control group comprised of unmodified specimens. Direct culture method was used to assess C. albicans adhesion. A profilometer and Vickers hardness test were used to measure surface roughness and hardness respectively. Analysis of variance (ANOVA) and post hoc Tukey’s test were used for data analysis (α = 0.05).ResultsBAG addition significantly decreased the C. albicans count when compared with the control group (P < 0.001) for both HP and AP. Regarding surface roughness, there was no change in the HP acrylic resins (P > 0.05), while the AP acrylic resins exhibited significantly higher surface roughness with BAG addition (P < 0.001). The hardness of the HP and AP acrylic resins were significantly higher with the addition of BAG (P < 0.001).ConclusionsThe addition of BAG to HP and AP acrylic resins effectively decreases C. albicans adhesion. The roughness of AP acrylic resins increases with the addition of BAG, while the hardness of both HP and AP acrylic resins increase with the addition of BAG.     

鸦胆子油软胶囊联合SOX方案治疗晚期结直肠癌的临床研究

目的研究鸦胆子油软胶囊联合SOX方案(奥沙利铂+替吉奥)治疗晚期结直肠癌的临床疗效。方法选取2018年8月-2019年8月在郑州大学附属洛阳中心医院治疗的80例晚期结直肠癌患者,所有患者随机分为对照组和治疗组,每组各40例。对照组患者入院后给予SOX方案治疗,第1~14天给予注射用奥沙利铂,推荐剂量130 mg/m^2,溶于500 mL 5%葡萄糖溶液中,输注时间小于3h;第1~21天口服替吉奥胶囊,1粒/次,2次/d。治疗组在对照组基础上口服鸦胆子油软胶囊,4粒/次,3次/d。21 d为1个治疗疗程,两组患者接受治疗3个疗程。观察两组的临床疗效,比较Karnofsky(KPS)评分、生活质量(QOL)评分及血清癌胚抗原(CEA)、基质金属蛋白酶(MMP)-2和MMP-9水平。结果经过治疗后,治疗组客观缓解率(ORR)和疾病控制率(CBR)显著高于对照组(P<0.05)。治疗后,两组患者KPS评分和QOL评分显著升高(P<0.05),且治疗组KPS评分和QOL评分升高程度较大(P<0.05)。治疗后,两组CEA、MMP-2和MMP-9水平显著降低(P<0.05);并且治疗组降低较多(P<0.05)。治疗组胃肠道反应、血小板减少、白细胞减少和转氨酶升高等不良反应发生率明显低于对照组(P<0.05)。结论鸦胆子油软胶囊联合SOX方案治疗晚期结直肠癌具有较好的治疗效果,能够提高患者生活质量,降低肿瘤标志物水平,安全性较高,值得在临床上推广应用。     

碘对比剂引起急性肾损伤的相关危险因素分析

目的探讨不同程度碘对比剂后急性肾损伤的危险因素及其转归预后。方法筛选2016年4月1日至2019年8月31日于重庆医科大学附属第三医院住院期间发生碘对比剂后急性肾损伤(PC-AKI)的患者,按照急性肾损伤分层标准将其分为非严重损伤组(A组)和严重损伤组(B组),从基本人口学资料、基础疾病、药物使用情况、转归预后等方面分析两组患者的特点及差异。结果 1 920例患者中发生PC-AKI者90例,其中A组72例(80.00%),B组18例(20.00%),B组中最终需肾脏替代治疗(血液透析)干预者11例(12.22%)。A组与B组间一般情况、基础肾功能、碘对比剂的使用以及联用肾毒性药物、静脉水化量等观察指标无统计学差异。B组合并慢性疾病者更多,其中冠心病(55.56%vs 29.17%)、心肌梗死(27.78%vs 5.56%)患病率差异具有统计学意义(P<0.05),行血液透析的患者第一诊断为心肌梗死者占45.45%。65.85%的患者在使用对比剂后10 d内肌酐仍高于基线,54.54%的透析患者在出院时仍需透析治疗,81.81%的透析患者出院时死亡或放弃治疗。结论合并冠心病、心肌梗死的患者更容易发生严重PC-AKI,当合并这些疾病的患者使用碘对比剂时,临床医师应密切关注其肾功能的变化。PC-AKI的肾功转归较差,发生PC-AKI后需透析治疗的患者往往预后不良。     

Oxime K074 – in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides

Abstract

Oxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074.     

丝棉木种子化学成分及其抗肿瘤活性

目的 研究丝棉木Euonymus maackii Rupr.种子的化学成分及其抗肿瘤活性.方法 丝棉木种子95%乙醇提取物乙酸乙酯部位采用硅胶、D101、反相HPLC进行分离纯化,根据理化性质及波谱数据鉴定所得化合物的结构.MTT法测定其抗肿瘤活性.结果 从中分离得到10个化合物,分别鉴定为1β-甲基正丁酰氧基-2β-苯甲酰氧基-4α-羟基-6α-呋喃酰氧基-9β,12-二乙酰氧基-β-二氢沉香呋喃(1)、6α,9β,12-三乙酰氧基-1β,2β,8β-三苯甲酰氧基-β-二氢沉香呋喃(2)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正己酰氧基-β-二氢沉香呋喃(3)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正辛酰氧基-β-二氢沉香呋喃(4)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-正癸酰氧基-β-二氢沉香呋喃(5)、卫矛羰碱(6)、6α,12-二乙酸基-1β,9α-二乙酸(β-呋喃羧氧基)-4α-羟基-2β-2-甲基丁酯-β-二氢沉香呋喃(7)、6α,9β,12-三乙酰氧基-1β,8β-二苯甲酰氧基-2β-羟基-β-二氢沉香呋喃(8)、6α,12-二乙酸基-1β,9 α-二乙酸(β-呋喃羧氧基)-4α-羟基-1β-2-甲基丁酯-β-二氢沉香呋喃(9)、6α,9β,12-四乙酰氧基-1β,8β-二苯甲酰氧基-β-二氢沉香呋喃(10).化合物6对Hela细胞有明显的抑制作用,IC50为9.76 μg/mL.结论 化合物1为新化合物.化合物6有一定的抗肿瘤活性.     

Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.