中医药干预新型冠状病毒肺炎临床研究方案分析

对中医药防治新型冠状病毒肺炎临床研究方案注册情况进行分析,为提高相关研究设计质量提供参考和建议。检索中国临床试验注册中心网站(www.chictr.org.cn)以及美国临床试验注册中心网站(clinicaltrials.gov),以新型冠状病毒肺炎、2019-nCoV等为检索词,检索新型冠状病毒肺炎中医药相关临床研究方案。按照纳入排除标准筛选文献,并提取研究注册时间、研究目的、研究类型、申办单位、研究对象、样本量、干预措施、评价指标等数据,采用描述性分析方法。共纳入新型冠状病毒肺炎中医药相关研究方案49个,研究负责单位以湖北、北京、浙江等地医院或高等院校为主。研究具体实施单位属地集中在湖北、广东、浙江、河南等地医院。研究设计以干预性试验研究为主(共40个),其中随机平行对照研究30个,非随机对照试验7个,单臂研究2个,连续入组1个;观察性研究6个;卫生服务研究2个;预防性研究1个。总样本量30562例,单个研究样本量最大20000例,最小30例。49个方案的研究对象包括健康人群(3个)、隔离观察人群(1个)、疑似病例(10个)、确诊病例(31个)、康复期病例(4个)。31个拟纳入确诊病例的研究方案中,有16个研究未明确病情分级,3个研究明确排除危重症,4个研究纳入普通型,2个研究纳入轻型、普通型或重型,1个研究纳入轻型和普通型,1个研究纳入普通型或重型,3个研究纳入重型,1个研究纳入重症或危重症。评价的干预措施包括中成药(连花清瘟胶囊/颗粒、藿香正气滴丸/口服液、八宝丹、固表解毒灵、金蒿解热颗粒、复方鱼腥草合剂、金叶败毒颗粒、疏风解毒胶囊、双黄连口服液、痰热清注射液、血必净注射液、热毒宁注射液、喜炎平注射液)、汤药、太极拳疗法。主要疗效指标以退热时间、临床症状缓解、新型冠状病毒核酸转阴、重症转化率、胸部CT影像为主。结果表明中医药防治新冠肺炎的临床研究响应快速,当前注册方案涵盖了疾病预防、治疗和康复全过程。但存在人群定义不清,研究目标不明确,干预方案需要细化,疗效评价指标需要优化等问题;另外,需要考虑疫情救治的实际困难和工作负担,在符合医学伦理条件下,优化流程,提高研究方案的可操作性。     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.     

老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效对比

目的：探讨老年人桡骨远端C型骨折的手术治疗与非手术治疗的疗效差异，评价两种方法的优缺点。方法回顾性分析2009-12—2011-12收治的老年桡骨远端C型骨折68例，按照治疗方法分为A组(手术组)及B组(非手术组)，统计分析两组患者的临床资料。结果 A组33例， B组35例，平均随访21.5个月。两组患者的年龄、骨折类型均无差异(P＞0.05)；术后影像学指标A组优于B组，骨折愈合时间B组优于A组，治疗成本A组大于B组(P＜0.05)；Cooney评分早期A组优于B组，1年后两组无差异，两组的并发症无差异(P＞0.05)。结论老年人桡骨远端C型骨折手术治疗较非手术治疗可获得更好的复位及早期功能，但远期功能恢复无差异。     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.