不同类型研究设计在卫生决策中的应用情况

传统上,卫生监管部门和卫生技术评估（HTA）组织将随机对照试验（RCT）视为证明疗效和安全性的黄金标准,但不同类型的研究设计根据自身特点适用于不同的研究目的和研究类型,本文对各国卫生技术评估中提交证据研究设计类型的要求进行总结,并以CADTH为例具体分析其应用情况,发现RCT仍是目前提交的主要证据类型,但越来越多的Ⅰ/Ⅱ期试验和包括真实世界证据在内的非RCT证据正逐渐参与到卫生决策中来,在慢病和癌症领域尤为明显。随着非RCT证据在数据整合、偏倚控制等方面的完善,相信其将会和高质量的RCT证据一同在卫生评估中发挥更重要的作用。     

药物重定位候选药物筛选路径

相对传统新药研发模式,药物重定位策略发现药物新用途具有显著的成本效益优势,能加快药物上市步伐,满足恶性肿瘤、罕见病、个性化医疗等特定领域药物临床用药需求,因而被各界关注。本文主要介绍了药物重定位的一般流程与候选药物筛选路径,如从非理性设计方法向基于相似性、基于结构虚拟筛选、推理与机器学习等理性设计方法发现重定位药物的系统性转变。     

多体素磁共振频谱技术在海马硬化中的应用

目的评价磁共振多体素频谱技术在早期海马硬化中的应用价值。方法对28例单侧颞叶癫痫患者行常规MR及双侧海马区多体素频谱检查,测量双侧海马区域N-乙酰天门冬氨酸、胆碱、肌酸的信号强度,分析双侧海马区代谢物的分布情况。结果 1常规MR检查示4例单侧海马萎缩,4例诊断侧别不一致,20例海马形态学未见改变;2患侧NAA、NAA/Cho、NAA/Cr、NAA/(Cho+Cr)值较对侧均明显降低,差异有统计学意义。结论多体素磁共振频谱技术能够早期发现海马硬化,进而可对癫痫灶进行准确定位。     

偏心髋臼旋转截骨术的生物力学机制及初步临床疗效

 目的 探讨偏心髋臼旋转截骨术治疗髋关节发育不良的生物力学机制及其初步临床疗效。方法 取6具经福尔马林防腐处理的女性尸体骨盆标本,建立髋关节生物力学模型,在模型上模拟偏心髋臼旋转截骨术。对骨盆缓慢施加连续纵向压力0~500 N,测量术前和术后载荷100、200、300、400、500 N时的股骨头承重区应变值,计算应力值。2007年7月至2014年10月应用偏心髋臼旋转截骨术治疗髋关节发育不良25例（26髋）,男6例,女19例;年龄11~57岁,平均31岁。术后以Harris髋关节评分评价髋关节功能,摄骨盆正位X线片测量头臼指数、中心边缘角（center-edge-angle,CE角）及Sharp角。结果-随着脊柱纵向压力加大,股骨头上的应力值随之增加。偏心髋臼旋转截骨术后应力值在载荷超过300 N后由上升趋势转变为下降趋势,总体呈抛物线状。100~500 N载荷下偏心髋臼旋转截骨术后的应力值与术前差异均无统计学意义。临床随访18例（19髋）,随访率72%。随访时间7~85个月,平均40个月。Harris髋关节评分由术前（64.3±7.2）分提高至末次随访时（85.6±5.3）分;头臼指数平均增加36.5%、CE角平均增加33.1°、Sharp角平均减少12.3°,与术前比较差异均有统计学意义。结论-偏心髋臼旋转截骨术具有较好的矫正髋臼畸形的能力,可增大股骨头的髋臼覆盖面和降低承重区压力。     

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.     

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na~+ channels of cortical neurons is time-and dose-dependent

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations(0.1, 1, 5 and 10 ng/m L) and the effects of 10 ng/m L interleukin-6 exposure to cortical neurons for various durations(2, 4, 8, 24 and 48 hours) by studying voltage-gated Na+ channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na+ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na+ channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.     

Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury

In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator(TIGAR) protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation(OGD)/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages(E16 and E20).The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate(NADPH) significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.