A framework for considering the risk‐benefit trade‐off in designing noninferiority trials using composite outcome approaches

When a new treatment regimen is expected to have comparable or slightly worse efficacy to that of the control regimen but has benefits in other domains such as safety and tolerability, a noninferiority (NI) trial may be appropriate but is fraught with difficulty in justifying an acceptable NI margin that is based on both clinical and statistical input. To overcome this, we propose to utilize composite risk‐benefit outcomes that combine elements from domains of importance (eg, efficacy, safety, and tolerability). The composite outcome itself may be analyzed using a superiority framework, or it can be used as a tool at the design stage of a NI trial for selecting an NI margin for efficacy that balances changes in risks and benefits. In the latter case, the choice of NI margin may be based on a novel quantity called the maximum allowable decrease in efficacy (MADE), defined as the marginal difference in efficacy between arms that would yield a null treatment effect for the composite outcome given an assumed distribution for the composite outcome. We observe that MADE: (1) is larger when the safety improvement for the experimental arm is larger, (2) depends on the association between the efficacy and safety outcomes, and (3) depends on the control arm efficacy rate. We use a numerical example for power comparisons between a superiority test for the composite outcome vs a noninferiority test for efficacy using the MADE as the NI margin, and apply the methods to a TB treatment trial.     

LncRNA PCED1B-AS1调控NLRP3促进巨噬细胞清除结核分枝杆菌的机制研究

目的　研究长链非编码RNA PCED1B-AS1调控核苷酸结合寡聚化结构域样受体3（NLR family pyrindomain containing 3, NLRP3）对巨噬细胞清除结核分枝杆菌和分泌炎症因子的影响。方法　在巨噬细胞RAW264.7中转染pcDNA-PCED1B-AS1,并用结核分枝杆菌感染,qRT-PCR方法检测PCED1B-AS1和TNF-α、IL-6 mRNA水平,用菌落形成实验检测巨噬细胞对结核分枝杆菌的清除作用,Western blot方法检测细胞中NLRP3蛋白表达水平。将NLRP3 小干扰RNA（small interfering RNA, siRNA）和pcDNA-PCED1B-AS1共转染到巨噬细胞中,用结核分枝杆菌感染,同样检测细胞中TNF-α、IL-6 mRNA水平和菌落量。结果　结核分枝杆菌感染后的巨噬细胞中PCED1B-AS1水平降低,TNF-α、IL-6 mRNA水平升高。转染pcDNA-PCED1B-AS1后的巨噬细胞经过结核分枝杆菌感染以后,细胞中PCED1B-AS1、TNF-α、IL-6 mRNA水平升高,形成的菌落量减少,细胞中NLRP3蛋白表达水平升高。NLRP3 siRNA可以逆转过表达PCED1B-AS1对结核分枝杆菌感染的巨噬细胞中TNF-α、IL-6 mRNA表达和菌落量形成的影响。结论　上调PCED1B-AS1促进巨噬细胞清除结核分枝杆菌,诱导细胞表达TNF-α、IL-6 mRNA的机制与上调NLRP3表达有关。     

2010—2019年新疆伊宁市初治涂阳肺结核患者流行特征及治疗转归分析

目的 了解2010—2019年新疆伊宁市初治涂阳肺结核流行特征,并分析影响其治疗结局的因素,为该地区的结核病疫情防控提供理论依据。方法 通过《中国结核病管理信息系统》收集伊宁市2010—2019年初治涂阳肺结核患者的基本信息、治疗及诊断信息。人口学信息来源于2010—2019年《伊犁州统计局统计年鉴》,流行特征分析采用描述性流行病学方法,并采用多因素logistic回归模型分析纳入患者治疗转归的影响因素。结果 2010—2019年新疆伊宁市共报道了4728例初治涂阳肺结核病患者,年均报告发病率为87.16/10万,各年度报告发病率范围为66.55/10万（391例）~127.29/10万（727例）,在4728例初治涂阳患者中,HIV检查阳性患者共665例,HIV-TB双重感染年均登记报告率为12.57/10万;男性2922例,女性1806例,男性与女性的比例为1.62∶1;16~45岁［66.96%(3166/4728)］、少数民族［84.40%（3973/4728）］人群多发;患者来源主要以转诊为主,占比为42.49%（2009/4728）;患者主要为Ⅲ型肺结核［94.20%（4454/4728）］;初治涂阳肺结核流行期集中在每年的3—5月;多因素logistic回归结果显示:强化期督导（OR=0.015,95%CI:0.003~0.077）、全程督导（OR=0.067,95%CI:0.014~0.314）、全程管理（OR=0.045,95%CI:0.004~0.526）、系统管理（OR<0.001,95%CI:0.000~0.001）的初治涂阳肺结核患者更易治疗成功。结论 2010—2019年伊宁市初治涂阳肺结核报告发病率总体上呈现先下降后上升的趋势,应重点关注男性、中年、少数民族人群,在3—5月期间对以上高危人群进行结核病筛查;加强初治涂阳肺结核患者治疗过程中的系统管理和督导工作。     

TCI管理软件的设计与实现

目的本文介绍了结核病管理软件管理系统的结构组成、功能和主要技术,使用意义。材料与方法:以WINDOWS为开发平台,用VFOXPRO6。0设计出用于结核病管理的应用软件。结果:该软件可用于病人登记、查询、统计、统计分析以及管理。结论:用微机进行结核病人管理具有重要意义。     

Rapid detection of resistance in Mycobacterium tuberculosis: a review discussing molecular approaches

The last few years have seen the development of several molecular designs to search for mutations encoding resistance to antituberculous drugs in Mycobacterium tuberculosis . Most of these are highly efficient for RIF-r detection and are well adapted to search for the most relevant INH-R mutations. In this review, these new molecular approaches are explained and are presented according to the molecular strategies on which they are based. In this sense, techniques based on DNA-sequencing, electrophoresis and hybridization are reviewed and the newer designs based on real-time PCR and microarrays are also included. Molecular methods are sure to transform standard approaches to the issue of resistance in the mycobacteriology laboratory. This will allow laboratories to speed up the performance of resistance assays and provide access to essential information for highly refined detection, follow-up and management of antibiotic resistance in M. tuberculosis .     

临沂市尘肺合并肺结核调查分析

目的 探讨尘肺合并肺结核的发病特点。方法 对历年来职业病档案中的现患及死亡病例逐个核实统计。结果 ①单纯尘肺560例,尘肺合并肺结核156例,合并率为21．79%。②退伍工程兵合并结核病死亡率高于厂矿企业工人。③尘肺合并肺结核死亡高于其他疾病。结论 ①尘肺合并肺结核率随期别的增加而显著增高;②尘肺合并肺结核发病率随年代的增加而降低;③尘肺合并肺结核死亡率高于单纯尘肺死亡率,随尘肺期别的增加而增高;④尘肺合并肺结核死亡所占比例随年代的增加而显著降低。     

住院肺结核病人耐药状况与疗效分析

目的　了解结核病医院中住院病人的耐药及多耐药结核病 ( MDR-TB)流行情况、特点及影响因素。方法　用临床流行病学方法进行统计和分析。结果　耐药率为 3 0 .71 % ,MDR-TB发病率为1 1 .68% ,初始 MDR-TB为 2 .55% ,继发 MDR-TB为 9.1 3 % ,MDR-TB死亡率为 9.4 8%。结论　耐药及MDR-TB发病率逐年增加 ,高死亡率。     

结核分枝杆菌DNA两种提取方法比较

目的 :比较能够满足内切酶分析的结核分枝杆菌染色体DNA提取的两种方法 ,并结合实验室条件加以改进。方法 :称取结核分枝杆菌培养物 ,灭活后以溶菌酶和蛋白酶K消化后 ,分别以CTAB/NaCl和酚 /氯仿 /异戊醇 (2 5∶2 4∶1)抽提 ,无水乙醇沉淀 ,紫外分光光度计测定DNA的含量。结果 :酚抽提法和CTAB抽提法提取的基因组DNA的得率分别为0 47± 0 0 71,0 41± 0 10 (‰ ,W/W )。A2 60 /A2 80 的值分别为 1 83± 0 12 ,1 89± 0 0 72。结论 :用CTAB/NaCl抽提结核分枝杆菌基因组DNA均能满足内切酶及杂交操作的要求 ,酚抽提法得率稍高 ,但无统计学意义。CTAB法污染少 ,省时省材 ,可代替酚抽提DNA。     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

59例老年人肺结核临床特点分析

目的 探讨老年人肺结核病的临床特点,方法 回顾性分析了５９例６０岁以上老年肺结核的临床表现、肺Ｘ线特征、诊断及效果。结果 ①５９例患以肺结核诊断入院２１例（３５．６％）,其他疾病（非结核病）入院３８例（６４．４％）,其中１４例为复发性肺结核;②５４例（９１．５％）合并有不同脏器疾病;③４４例经抗结核治疗后治愈或好转,总有效率为７４．６％;④死亡７例（１３．４％）,其中因确诊晚未及治疗的３例,