Data integration,analysis, and interpretation of eight academic CLARITY-BPA studies

“Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA) was a comprehensive “industry-standard” Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically – and toxicologically – relevant.     

An assessment of weight change associated with the initiation of a protease or integrase strand transfer inhibitor in patients with human immunodeficiency virus

Abstract

Objective

Evidence suggests that integrase strand transfer inhibitors (INSTIs) are associated with greater weight gain than other antiretrovirals. This real-world study compares weight/body mass index (BMI) change between insured US patients with human immunodeficiency virus (HIV-1) initiating a protease inhibitor (PI) or INSTI.     

布洛芬混悬滴剂和对乙酰氨基酚治疗小儿热性惊厥的疗效观察

目的 观察布洛芬混悬滴剂和对乙酰氨基酚治疗小儿热性惊厥(FS)的疗效。方法 选取2017年4月—2019年4月于本院就诊的FS患儿80例,随机分为对照组与观察组,每组40例,均进行抗惊厥、物理降温等常规治疗,在此基础上,对照组采用对乙酰氨基酚治疗,观察组采用布洛芬混悬滴剂治疗,观察2组临床疗效、退热效果、实验室检查结果(血红蛋白、血钠、血钙)及不良反应情况。结果 对照组治疗总有效率为77.5%,观察组为95%,差异有统计学意义(P<0.05);治疗后1 h,2组患儿体温差异无统计学意义(P>0.05),治疗后3 h、6 h,2组体温均低于服药前,观察组患儿体温低于对照组,差异有统计学意义(P<0.05);治疗后,2组血红蛋白、血钠、血钙浓度较服药前均显著升高(P<0.05),且观察组高于对照组(P<0.05);对照组不良反应率为7.5%,观察组为5%,差异无统计学意义(P>0.05)。结论 布洛芬混悬滴剂对小儿热性惊厥临床症状改善作用显著,值得推介。     

Efficacy,safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management.     

男性乳腺癌患者生物治疗前真实心理体验的质性研究

目的：探讨男性乳腺癌患者生物治疗前真实心理体验。方法用质性研究中的现象学方法，以半结构式进行深度访谈，收集10名男性乳腺癌患者生物治疗前的真实体验，采用现象学7步分析法分析资料。结果得到6个主题：不良心理反应；消极应对方式；沉重的经济负担；缺乏生物治疗相关知识；对治疗的不确定感；寻求心理支持。结论深入了解男性乳腺癌患者的内心世界，有助于护理人员更好地去理解和尊重患者，为制定个体化、人性化护理方案提供理论依据。     

Role of phytoestrogens in prevention and management of type 2 diabetes

Type 2 diabetes(T2D)has become a major public health threat across the globe.It has been widely acknowledged that diet plays an important role in the development and management of T2D.Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties.Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogendependent and estrogen-independent pathways.In the current review,we have summarized the evidence linking two major types of phytoestrogens,isoflavones and lignans,and T2D from epidemiological studies and clinical trials.The cross-sectional and prospective cohort studies have reported inconsistent results,which may due to the large variations in different populations and measurement errors in dietary intakes.Long-term intervention studies using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women,while results from short-term smallsize clinical trials are conflicting.Taken together,the current evidence from different study designs is complex and inconsistent.Although the widespread use of phytoestrogens could not be recommended yet,habitual consumption of phytoestrogens,particularly their intact food sources like soy and whole flaxseed,could be considered as a component of overall healthy dietary pattern for prevention and management of T2D.     

有机磷农药与再生障碍性贫血发病关系的Meta分析

目的 评价有机磷农药与再生障碍性贫血发病的关系,为一级预防提供科学依据。方法 检索1990年1月至2014年8月公开发表在中国生物医学文献数据库(CBM)、中国知网(CNKI)、PubMed和EMBASE关于有机磷农药与再生障碍性贫血发病关系的病例对照研究。制定纳入和排除标准,对符合纳入标准的文献进行质量评价,利用Review Manager 5.0软件计算有机磷农药的合并OR值及其95%CI,并对文献的研究人群和有机磷农药使用方式进行亚组分析。结果 最终共纳入9篇文献,5 833例研究对象,其中病例组1 404人,对照组4 429人。结果显示有机磷农药可增加再生障碍性贫血的发病风险(OR=1.97,95%CI:1.60～2.44)。亚组分析显示亚洲人群再生障碍性贫血的发病风险(OR=2.01,95%CI:1.52～2.66)高于欧美人群(OR=1.93,95%CI:1.39～2.67);使用单一有机磷类农药(OR=2.15,95%CI:1.60～2.88)比使用有机磷类农药的混配制剂(OR=1.82,95%CI:1.34～2.47)更易引发再生障碍性贫血。结论 有机磷农药可能是再生障碍性贫血的危险因素。在日常生活和工农业生产中,减少有机磷农药的暴露,可以预防再生障碍性贫血的发生。