目的 通过比较一般线性模型、广义估计方程及混合效应模型在医疗器械试验定量指标纵向数据中的估计效果,探讨合适分析方法并提供参考.方法 以非劣效支架试验为例并结合应用蒙特卡洛随机模拟的方法,模拟不同样本量、不同数据相关程度及不同相关数据比例下的纵向数据,比较不同模型应用的准确性.结果 在不同数据相关程度及相关数据比例下,不同模型所得能获得阳性结果的概率变化规律有所不同.一般线性模型所得假阳性错误率随着相关数据比例的增加而增大,且大于0.05;而广义估计方程和混合效应模型所得假阳性错误率稳定在0.05附近.结论 对于相同定量指标纵向数据,建议结合实际数据特点,采用广义估计方程或混合效应模型进行分析,确保准确地估计组间真实疗效.

探索帕博利珠单抗(Pembrolizumab)与紫杉醇比较在PD-L1阳性晚期胃/胃食管结合部腺癌临床疗效和安全性的两项全球多中心、随机对照、Ⅲ期研究(Keynote-061和062)均以失败告终,导致FDA撤销了 Keytruda(可瑞达)在该适应证上的应用.两项研究样本量分别为592例和763例,主要终点均为总生存(overall survival,OS).结果显示:帕博利珠单抗单药对比紫杉醇二线治疗PD-L1联合阳性分数(combined positive score,CPS)≥1患者中两组中位总生存期分别为9.1个月和8.3个月,风险比(hazard ratio,HR)为 0.82(95％CI:0.66～1.03,P=0.042 1),中位无进展生存期(progression-free survival,PFS)分别为1.5个月和4.1个月,风险比为1.27(95％CI:1.03～1.57);一线治疗的患者(CPS1)帕博利珠单抗OS非劣效于化疗,HR为0.91(99.2％CI:0.69～1.18),PFS风险比为1.66(95％CI:1.37～2.01);帕博利珠单抗联合化疗组相比化疗疗效改善没有明显优势,OS风险比为0.85(95％CI:0.70～1.03);PFS风险比为0.84(95％CI:0.70～1.02).但在安全性方面,帕博利珠单抗相对于化疗均表现出较好的安全性.帕博利珠单抗单药在晚期胃/胃食管结合部腺癌的研究结果为阴性,其研究策略、方案设计、统计分析、后续布局等均值得进一步讨论和思考.

目的:通过文献检索和Meta分析方法为上市前药物洗脱球囊(DEB)导管治疗冠状动脉分支病变相关临床试验提供样本量依据.方法:目前仅有辽宁垠艺生物科技股份有限公司生产的轻舟?(Bingo?)DEB导管被国家药品监督管理局(NMPA)批准用于分支病变治疗,故可采用随机对照试验的非劣效性设计,主要评价指标为术后9个月随访时基于造影获得的分支血管靶病变节段内直径狭窄百分比(DS％).根据产品和适应证等设定关键词检索组合,对同品种产品开展文献检索和筛选,用Meta分析方法整合已上市同类产品结果,为上市前DEB导管随机对照试验的样本量计算提供效应值、非劣效界值等依据.结果:共计筛选106篇文献,最终符合入排标准共计10篇文献(含9项研究),其中报告术后9个月DS％ 的5项研究,结合临床实际和Meta分析合并同品种产品研究的结果,假设两组DEB导管能够达到同样的DS％ 水平,即Meta合并效应值点估计27.74％,并基于所有单项研究报道结果保守估计标准差设置为 ±18.00％,结合4项DEB导管与普通球囊相比较的术后DS％ 均差Meta结果为-9.61％(95％CI:-15.29％～-3.93％),再结合临床考虑设定非劣效界值在7.00％,并以此为基础计算出最终每组需入选140例,两组共计280例.结论:以DEB导管治疗冠状动脉分支病变为例,采用文献检索和Meta分析方法可为临床试验的样本量估算提供更为稳妥的文献支持.

Objective: Statistical significance plays an important role in the interpretation of clinical trial results. However, on the basis of obtaining statistical significance, the assessment of clinical significance is often neglected. This study attempted to propose a simple and unambiguous new classification method for study results, focusing on studies with statistical positive findings to evaluate whether the results have clinical significance. Methods: Our study subjects were the clinical studies in 2019 ACC and ESC annual meetings. Meta-epidemiology methods were used to extract the characteristic variable from each study. The primary evaluation indicators included target effect-size and observed effect-size. Based on the difference between the two indicators, the studies that had statistical significance were subdivided to identify studies with possible insufficient clinical significance; Furthermore, the theoretical threshold based on power analysis was proposed, which was used as the basis for the interpretation of study results. Results: There were 12 clinical studies included in the final analysis. All of them were published on top journals. Those studies had relative high quality on both study design and reporting. The correlation coefficient between the observed and target effect-size was 0.892. Among the 7 studies with statistical significance, two of them were classified as insufficient clinical significance. The counts was 1 (1/3) and 1 (1/4) for the studies reported in ACC and ESC respectively. Conclusions: The achievement of clinical significance is critical even in the study with positive results. This paper proposes a new classification standard that combines clinical significance with statistical significance and further suggests a method to evaluate the reliability of clinical study results in order to assist researchers in identifying potential risks caused by insufficient clinical significance, and provide some reference and help for the reasonable interpretation of clinical study results.

Abstract Background To survey the relationship between salt intake and blood pressure in hypertensive patients in Beijing. Methods A cross-sectional survey was used. Essential hypertensive patients were enrolled and divided into three groups (low, medium, and high salt intake) according to their 24 h urinary sodium excretion, which was used to access the salt intake. Blood pressure was measured through office measurement and ambulatory blood pressure monitoring. Results A total of 2,241 patients were enrolled with a mean age of 59.5 ± 13.8 years, mean blood pressure of 141.1 ± 18.5/84.6 ± 12.7 mm Hg, and urinary sodium excretion of 163.9 (95% CI 160.3–167.4) mmol [equal to salt intake 9.59 (9.38–9.79) g/d]. There were 1,544 cases from tertiary hospitals and the other 697 cases from community hospitals. Patients from community hospitals took more salt than patients from tertiary hospitals. Patients with high salt intake were younger than patients with low and medium salt intake. There were more males in high salt intake group than in the other two groups. Ambulatory blood pressure monitoring showed that patients with high salt intake had higher mean blood pressure not only in daytime, but also at night. The diastolic blood pressure in patients with medium salt intake was higher than that in patients with low salt intake. Conclusions Higher salt intake was associated with higher ambulatory blood pressure in hypertensive patients. More effort should be made to lower salt intake to improve blood pressure control rate.

Meta分析是系统评价的重要方法.随着循证医学的发展,Meta分析研究越来越多,解读Meta分析报告已成为获取医学前沿信息的重要方法之一,掌握Meta分析方法对于临床医生从事临床和科研工作大有裨益.本文通过实例对森林图、偏倚评价图和漏斗图的解读进行详细说明,并对异质性、稳健性和样本量的评估方法进行介绍,以期帮助临床医生正确掌握Meta分析文章的解读方法.

Objective:To systematically review the methodology in clinical trial-based health economics study with cost-effectiveness ratio for nutritional drug.Methods:The literature on health economics study for nutritional drug was retrieved from PubMed and Wanfang Medical Network by October 2019. The literature was selected according to inclusion and exclusion criteria, and was assessed using the Cochrane Risk Bias Assessment Tool and Newcastle-Ottawa Scale. Its methodology such as participants and grouping, confounding factors, research perspective, cost accounting, health outcomes and health economics analysis methods, sensitivity analysis, etc, was systematically reviewed as well.Results:Four target literatures were included in this study. The participants were from gastroenterology, gastrointestinal surgery, etc. Random grouping, regression, propensity score matching method, etc, were used to control confounding factors. The research perspective needed to be clear according to the principle of health economics study. The present literatures focused on "direct medical costs" , and calculated cost-effectiveness ratio or incremental cost-effectiveness ratio to evaluate the economics of medical interventions.Conclusion:The evidence of high-quality health economics research in parenteral and enteral nutrition area in China needs to be promoted, especially in the control of confounding factors, the choice of research perspective and sensitivity analysis, which are supposed to be explored by multidisciplinary research teams in practice.

目的:分析近十年中国心血管领域主要指南的推荐分类和证据水平分布,及基于中国研究的证据比例.方法:检索近十年(2010年1月1日至2020年5月31日)国内学会发布的主要心血管相关指南,筛选满足纳入标准的18篇涉及冠心病、高血压、心力衰竭、心肌病和瓣膜病等疾病的指南,提取推荐意见分类和证据水平等相关数据后进行分析.结果:18篇指南共包含1575条推荐,其中Ⅰ类推荐56.3％,Ⅲ类推荐5.7％;A级证据[多个随机对照试验(RCT)或其荟萃分析]比例22.7％,C级证据高达44.0％;各个指南"推荐分类-证据水平"组合的分布呈现较大的变异:肥厚型心肌病指南中没有Ⅰ-A推荐,而中国高血压防治指南Ⅰ-A推荐高达40.0％以上.有4篇(22.2％)指南未在推荐后标注相应的参考文献;其他14篇指南共标注有1132篇参考文献,平均每条推荐约标注0.85篇;来自中国的参考文献有180篇(15.9％),其中40篇为中国其他指南或共识,中国RCT仅有62篇(5.5％).高血压指南采用中国RCT证据比例最高(9.3％),而瓣膜心脏病指南中没有中国RCT证据的支持.结论:相对于美国心脏病学院/美国心脏协会(ACC/AHA)有约9.0％的A级证据,我国心血管指南中有超过五分之一的推荐为A级证据;中国心血管病指南参考文献标注不规范,且缺少来自中国RCT研究的证据.

Global leading scholars in the field of parenteral and enteral nutrition have been seeking for the criteria of diagnosis of malnutrition. In determining the diagnostic criteria for malnutrition, it is also necessary to take into account the normal values and clinically obtained cut-off points of different countries and races. The Global Leadership (nutrition field) Initiative on Malnutrition, GLIM) diagnostic criteria published online on Sep. 2 & Sep.3 2018. In January & February 2019, the [American Society for Parenteral and Enteral Nutrition, ASPEN] and the [European Society for Clinical Nutrition and Metabolism, ESPEN] published in print. The GLIM criteria has also been recorded in [National terminology of parenteral and enteral nutrition of China-2019]. In 2016 "Disease Classification and Code (Chinese expanding version of ICD-10)" having "nutritional risk" and "malnutrition" items officially listed. In 2019 " Notice on National Tertiary Public Hospitals" and in the "National Medical Insurance Administration-coding standard" also include the items of "nutritional risks " and "malnutrition" as diseases name.Although promoting individualized medical therapy in China now, but the actual situation of each clinical department is different. As far as parenteral and enteral nutrition is concerned, it was far from "precision medicine" or "targeted therapy " in clinical practice nowadays. The current aim is to identify which patients need nutrition support therapy for reasonable application - benefit to patient. China's DRG being developed by "big data survey system" . Therefore, it is necessary for "this system" can find nutritional risk and malnutrition as diseases name with the codes from Chinese expanding version of ICD-10. So, nutritional risk and malnutrition need to be filled in the cover page of discharged medical record.

目的 比较不同类型临床研究中临床事件委员会和研究者对不良事件判定的差异,以评估临床事件委员会在临床研究中的作用.方法 采用中国前瞻性城乡流行病学研究和两项药物临床试验数据,比较临床事件委员会评判结果与各中心研究者上报不良事件结果,并进行不一致率评估.结果 中国前瞻性城乡流行病学研究组于2018年2月至2019年6月共计召开11次临床事件委员会议,共评估终点事件1993例次,临床事件委员会和研究者判断不一致76例次,占3.8％;某药物Ⅰ期临床试验共计上报不良事件20例次,临床事件委员会和研究者判断不一致5例次,占25.0％;某药物Ⅲ期临床试验共计上报不良事件197例次,临床事件委员会和研究者判断不一致48例次,占24.4％.结论 本研究结果显示召开临床事件委员会进行不良事件审评,可按统一标准提高多中心临床研究不良事件评估的质量和可靠性.

目的 了解中国老年急性心肌梗死(AMI)患者住院期间及出院后2年调脂药物的应用现状及依从性.方法 纳入中国急性心肌梗死注册研究中2013年1月1日～2014年9月30日108家医院入选的AMI患者共26 625例,年龄缺失30例,按年龄分为老年组(年龄＞65岁)11 574例和中青年组(年龄≤65岁)15 021例,患者出院后1、6、12、18和24个月时进行随访,比较2组住院期间、出院时及出院后2年内调脂药物的应用和依从性.结果 与中青年组比较,老年组女性比例明显升高、体质量指数更低、高血压、糖尿病、既往心肌梗死、既往脑卒中史、外周血管疾病史、慢性肾功能不全比例更高(P =0.000).老年组高脂血症比例明显低于中青年组、但一直治疗和应用他汀类药物比例高于中青年组(6.3％vs 9.4％,23.4％ vs 15.1％,29.7％ vs 21.6％,P＜0.01).老年组急诊再灌注治疗比例明显低于中青年组(37.7％ vs 51.1％,P＜0.01).住院期间,老年组他汀类药物使用率(88.4％ vs90.5％)、他汀类负荷率(28.0％ vs 30.8％％)和非他汀类调脂药物使用率(1.5％vs 2.0％)均低于中青年组(P＜0.01).出院后,老年组他汀带药率低于中青年组(87.5％ vs 90.4％,P＜0.01).1、6、12、18和24个月随访时,老年组规律服药比例均低于中青年组(P＜0.05,P＜0.01);2组均以患者自停为主(比例＞80％);2组非他汀类调脂药物使用率低(比例≤0.6％).结论 老年AMI患者应用他汀类调脂药物为主,但用药比例低于中青年患者,且用药依从性随病程时间延长逐渐降低,应加强老年AMI患者的一二级预防.

Till 2020, parenteral and enteral nutrition in China has moved from Translation 1 (T1), and then Translation 2 (T2), to Translation 3 (T3) now. The T3 transfer requires the evaluation of medical services' quality and cost-effectiveness research. After learning from international published articles, the multicenter cooperative database group of Chinese Society for Parenteral and Enteral Nutrition (CSPEN) on Nutritional risk, Undernutrition, Support, Outcome, and Cost-effectiveness ratio (NUSOC) (abbreviated to CSPEN-NUSOC Cooperative Group) has made efforts to promote health economics research in the field of parenteral and enteral nutrition in China. This paper reviewed the translational medical research of parenteral and enteral nutrition in China. At present, clinical studies toward the goal of "reasonable use to benefit patients" should be conducted in parenteral and enteral nutrition field in China, such as clinical effectiveness study of nutritional risk screening 2002 and Global Leadership Initiative on Malnutrition criteria, or health economics study on nutritional drug.

随着我国人口老龄化的加剧,骨骼健康问题越来越受到人们的关注.骨质疏松症为最常见的骨骼健康问题,是一种以骨量低、骨组织微结构损坏导致骨脆性增加、易发生骨折为特征的全身性骨病 [1].骨质疏松症常发生在老年男性和绝经后女性人群中,是造成老年患者骨折而致残和致死的主要原因之一.对高危人群进行早期筛查与诊断并及时治疗,可有效降低骨质疏松症带来的危害.临床医生主要依据骨密度测量结果 和相关危险因素来诊断骨质疏松症并评估骨折风险,目前常用的骨密度测量设备包括双能X线骨密度测量仪、定量CT骨密度分析系统和超声骨密度仪.本文对这三种设备的技术及临床应用进展进行介绍和对比分析.

自21世纪初,经皮冠状动脉介入治疗(percutaneous coronary intervention, PCI)心血管疾病的年手术量已逼近八百万的数量级,按2001年开展的577767例计算,相当于在每100万人口中有1108例进行PCI术,且该数字以每年15％～25％的速度持续增长[1].药物洗脱支架(drug-eluting stent, DES)凭借其对支架内再狭窄的有效控制,成为当前PCI的"金标准"[2].但有研究表明,DES置入可能导致动脉粥样硬化过程加速、炎症反应和支架小梁断裂等风险[3].因此,近5年研究的热点逐渐转移到了以药物洗脱球囊(drug-coated balloon,DCB)和生物可吸收支架(bioresorbable scarfold, BRS)为代表的新型治疗器械[4-9].新型治疗器械可为血管提供"一过性"支撑、且没有永久的残留物,从而在理论上避免了残留物对血管造成的远期潜在影响[10-11].DCB及BRS的临床应用促进PCI进入了"介入无置入"的时代.

目的:探索中国≥60岁老年人群心率与心血管死亡、非心血管死亡及全因死亡风险的相关性.方法:本研究基于前瞻性城乡流行病学研究中国队列(PURE-China)的随访调查.针对60岁以上老年人群,在基线调查时通过数字血压计测量心率,在随访时通过标准化的病例报告表收集心血管死亡、非心血管死亡和全因死亡事件.所有入选者按照不同性别将心率作为分类变量,分为<60次/min组、60～69次/min组、70～79次/min组、80～89次/min组和≥90次/min组共5组,以60～69次/min组作为参照组.最终8487例纳入分析.采用Cox共享脆弱模型探索心率与死亡风险的相关性.结果:8487例年龄≥60岁的老年人中,男性3925例,占总人群的46.25％,平均心率为(73.2±11.6)次/min;女性4562例,占总人群的53.75％,平均心率为(75.8±10.9)次/min.经过63688人年(中位随访时间8.55年)的随访,共发生262例心血管死亡事件、399例非心血管死亡事件和682例全因死亡事件.心率增快与≥60岁老年人群死亡风险增加有关.以心率60～69次/min组为参照组,在≥60岁老年男性人群中,当心率>80次/min以上时,三个终点事件死亡风险均显著增加(P均<0.05),而在≥60岁老年女性人群中只有当心率≥90次/min时,心血管死亡(HR=2.04,95％CI:1.07～3.87)和全因死亡(HR=1.78,95％CI:1.18～2.71)风险才显著增加.结论:心率增快与我国≥60岁老年人群的死亡风险增加有关,该关联在男性和女性人群中存在一定的差异.

Objective: To evaluate the prognostic value of the thrombolysis in myocardial infarction (TIMI) and global registry of acute coronary events (GRACE) risk scores for in-hospital mortality in Chinese non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods: Data of present study derived from the prospective, multi-center registry trial of Chinese AMI (CAMI). Among 31 provinces, municipalities or autonomous districts in China, at least one tertiary and secondary hospital was selected. From January 2013 to September 2014, 5 896 consecutive non-ST-segment elevation myocardial infarction patients who were admitted to 107 hospitals within 7 days of symptom onset were enrolled. For each patient, TIMI and GRACE risk scores were calculated using specific variables collected at admission. Their prognostic value was evaluated by the endpoint of in-hospital mortality. Results: Among 5 896 NSTEMI patients (age was (65.4±12.1) years old), 68.2% (n=4 020) were males. The in-hospital mortality was 6.0% (n=353) and the median length of hospital stay was 10.0 (7.0, 13.0) days. The incidence of pre-hospital cardiac arrest was 3.6% (n=213) among 5 896 NSTEMI patients. Six hundreds and forty five patients (10.9%) received primary percutaneous coronary intervention, and 6 patients underwent emergent coronary artery bypass grafting surgery (0.1%), and the median time of reperfusion was 529.5 (256.0, 1 065.0) minutes. The prescription percentage of statins, β-blocker, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers, and aldosterone antagonists were 94.8% (n=5 587), 71.7% (n=4 228), 65.5% (n=3 864) and 26.0% (n=1 533) respectively. The area under the curve of GRACE risk score for in-hospital mortality (0.7930 (95%CI 0.767-0.818)) was better than that of TIMI risk score (0.5588 (95%CI 0.532-0.586), P<0.001). Conclusion: GRACE risk score demonstrates better predictive accuracy than TIMI risk score for in-hospital mortality in NSTEMI patients in this patient cohort.

在植入式骶神经刺激系统临床试验的技术审评中,应主要关注以下方面:临床试验基本原则、临床试验医疗机构要求和临床试验方案设计要素.

目的:探索中老年(≥40岁)高血压人群肥胖与骨质疏松的相关性.方法:本研究基于中国脊柱和髋状态(CASH)研究,共纳入中老年(≥40岁)高血压患者1394例.使用标准化问卷和定量CT扫描技术采集人体信息和腰椎骨密度数据.根据骨密度将人群划分为骨质疏松组(骨密度≤80 mg/m3)和非骨质疏松组(骨密度>80 mg/m3).采用二分类Logistic回归,分析体重指数、腰围、腰臀比、腰高比和身体形态指数与骨质疏松的相关性.结果:1394例研究对象的年龄范围为40～82岁,男性846例,女性548例;骨质疏松组478例,非骨质疏松组916例.校正模型中,总人群和女性患骨质疏松的风险与体重指数和身体形态指数均相关(P均<0.05),女性的身体形态指数与骨质疏松相关最强(OR=1.84,95％CI:1.28～2.64,P=0.001),其次为总人群中的身体形态指数(OR=1.72,95％CI:1.28～2.32,P<0.001).以第一分位数作为参照,女性中体重指数和身体形态指数各分位数组骨质疏松的趋势性检验P均<0.05;男性校正模型中未观察到统计学意义(P均>0.05).结论:与体重指数、腰围、腰臀比和腰高比相比,中老年高血压人群中身体形态指数与骨质疏松的相关性最强,尤其是在女性中,男性中尚未观察到统计学相关性.

Objective: To assess the relationship between bicycle ownership status and physical activity, time of sitting, overweight or obesity in China. Methods: Based on the information of China cohort from Prospective Urban Rural Epidemiology (PURE) study, we conducted a cross-sectional description. Multivariable linear and multivariable Logistic regression analysis were respectively used to distinguish the differences of physical activity, time of sitting, overweight or obesity status between bicycle owners and non-bicycle owners. Results: A total of 42 677 participants were analyzed, the average age was (51.23±9.72) years including 40.9% male. There were 27 744 (65.0%) bicycle owners, their MET-min/week for total physical activity, work, transportation,domestic and recreation time were 2513.00 (1114.00, 5271.00), 444.00 (0.00, 735.00), 420.00 (0.00, 990.00), 600.00 (180.00,1260.00) and 198.00 (0.00, 693.00) respectively; time of sitting was (1397.03±832.13) min/week and waist circumference was (81.03±10.53) cm. With adjusted potential confounders, bicycle owners had more transportation activity, while less total physical activity, work, domestic and recreation time than non-bicycle owners; bicycle owner had more time of sitting and less risk of obesity; BMI and waist-to-hip ratio were similar between bicycle owners and non-bicycle owners. Conclusion: Bicycle owners had more transportation related physical activity and less risk of obesity; while the total physical activity, domestic and recreation related physical activity might be reduced in them.