Comparison of the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.     

How the war on drugs impacts social determinants of health beyond the criminal legal system

There is a growing recognition in the fields of public health and medicine that social determinants of health (SDOH) play a key role in driving health inequities and disparities among various groups, such that a focus upon individual-level medical interventions will have limited effects without the consideration of the macro-level factors that dictate how effectively individuals can manage their health. While the health impacts of mass incarceration have been explored, less attention has been paid to how the “war on drugs” in the United States exacerbates many of the factors that negatively impact health and wellbeing, disproportionately impacting low-income communities and people of colour who already experience structural challenges including discrimination, disinvestment, and racism. The U.S. war on drugs has subjected millions to criminalisation, incarceration, and lifelong criminal records, disrupting or altogether eliminating their access to adequate resources and supports to live healthy lives. This paper examines the ways that “drug war logic” has become embedded in key SDOH and systems, such as employment, education, housing, public benefits, family regulation (commonly referred to as the child welfare system), the drug treatment system, and the healthcare system. Rather than supporting the health and wellbeing of individuals, families, and communities, the U.S. drug war has exacerbated harm in these systems through practices such as drug testing, mandatory reporting, zero-tolerance policies, and coerced treatment. We argue that, because the drug war has become embedded in these systems, medical practitioners can play a significant role in promoting individual and community health by reducing the impact of criminalisation upon healthcare service provision and by becoming engaged in policy reform efforts.

KEY MESSAGES

• A drug war logic that prioritises and justifies drug prohibition, criminalisation, and punishment has fuelled the expansion of drug surveillance and control mechanisms in numerous facets of everyday life in the United States negatively impacting key social determinants of health, including housing, education, income, and employment.
• The U.S. drug war’s frontline enforcers are no longer police alone but now include physicians, nurses, teachers, neighbours, social workers, employers, landlords, and others.
• Physicians and healthcare providers can play a significant role in promoting individual and community health by reducing the impact of criminalisation upon healthcare service provision and engaging in policy reform.

     

The role of the carrier in the formulation of pharmaceutical solid dispersions. Part II: amorphous carriers

ABSTRACT

Introduction: Amorphous solid dispersions are considered as one of the most powerful strategies to formulate poorly soluble drugs. They are made up of an active pharmaceutical ingredient (API) dispersed at the molecular level in an amorphous polymeric carrier. As the latter component constitutes the largest part of the formulation, its characteristics will contribute to a large extent to the properties and behavior of the solid dispersion.

Areas covered: Amorphous polymers are most often used in modern solid dispersion formulations. This review discusses carrier properties like molecular weight, conformation, hygroscopicity, their stabilization effects, issues related to solid dispersion manufacturing technology, response to downstream processing, and potential to generate supersaturation, next to criteria to select a carrier to formulate stable amorphous solid dispersions.

Expert opinion: Different amorphous carriers lead to solid dispersions with various properties in terms of physical stability, phase behavior and drug release rate and extent. Despite more than 50 years of intensive research in this field it remains difficult to predict what carrier is best suited for a given API, pointing to the complex nature of this formulation strategy. Sustained efforts to understand the link and complex interplay between material properties, processing parameters, physical stability and dissolution behavior are required from pharmaceutical scientists with a strong physicochemical background to shift the development from trial and error to science driven.     

计算机辅助药物设计在中药现代化中的应用

计算机辅助药物设计（CADD）是多学科交叉的边缘学科,在药物研发过程中起着枢纽作用,特别在先导化合物的发现和优化中发挥重要作用。中药现代化是当前我国中药产业发展之路,也是新药研发的有效途径。借助现代高新技术,特别是CADD技术,结合传统中医药理论进行中药研发,似可为中医药发展开辟一条适合我国国情的创新道路。本文主要探讨CADD在药物作用靶点的发现与验证以及中药现代化中的应用及其前景。     

我院Ⅰ类切口手术抗菌药物应用情况分析

目的 分析医院Ⅰ类切口手术抗菌药物预防性使用情况,加强Ⅰ类切口手术抗菌药物预防使用的控制和管理.方法 通过医院信息系统(HIS)统计2018年1-11月江苏省盐城市第一人民医院Ⅰ类切口手术数量和抗菌药物使用率,筛选出冠脉造影等血管介入诊断手术和重点监控Ⅰ类切口手术,统计其抗菌药物使用率,再通过电子信息化病历系统分析抗菌...     

全国9家肿瘤专科医院2010年抗肿瘤药利用分析

目的:评价全国9家肿瘤专科医院抗肿瘤药的应用情况。方法:采用回顾性方法,对全国9家肿瘤专科医院2010年抗肿瘤药的应用数据进行统计、分析。结果:所涉及的抗肿瘤药中,注射剂有68种,口服制剂有38种。口服制剂中,有27种出现用药频次错误。从处方单次用药剂量看,有40种药超出说明书用药剂量范围。结论:抗肿瘤激素药、铂类、紫杉烷类药应用最为广泛,分子靶向治疗药也应用较多。药品说明书应及时给予补充、修订、完善。     

赶黄草水煎液对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌生物膜形成的影响

目的 探究赶黄草水煎液在体外对金黄色葡萄球菌(SA)和耐甲氧西林金黄色葡萄球菌生物膜(MRSA)形成的影响。方法 采用微量肉汤稀释法测定赶黄草水煎液对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC),根据MIC和MBC绘制杀菌曲线,采用结晶紫染色法和激光共聚焦观察赶黄草水煎液对SA和MRSA生物膜形成的影响,并通过测定胞外多糖和胞外DNA的含量研究赶黄草水煎液破坏SA和MRSA生物膜的作用方式。结果 赶黄草水煎液对SA的MIC和MBC分别为1.36和2.71 mg/mL,对MRSA的MIC和MBC为2.71和5.73 mg/mL;赶黄草水煎液可使SA和MRSA均生长受到抑制,抑制生物膜的形成、减少胞外多糖和胞外DNA的释放。结论 赶黄草水煎液对SA和MRSA具有良好的抑菌作用,可通过抑制胞外多糖和DNA的分泌破坏生物膜的形成。     

Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys

Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis; a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis.     

选择性保护合成2-〔4(S)-4-酰氨基-3-氧代-2-异噁唑烷基〕-5-氧代-2-四氢呋喃甲酸类化合物及其体外抑菌活性

采用两种新选择性保护方法由L-丝氨酸和α-酮戊二酸为原料经几步合成了8个目标化合物。体外抑菌该验表明除TMV外,对金葡球菌209P和大肠杆菌44822具有中等到强的活性。