速效救心丸对比硝酸甘油治疗心绞痛急性发作疗效和安全性的系统评价

目的系统评价速效救心丸对比硝酸甘油治疗心绞痛急性发作的疗效和安全性。方法计算机检索PubMed、EMbase、Web of SCI、the Cochrane Library、中国知网(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据资源系统(WanFang Data)、中国生物医学文献服务系统(SinoMed)等数据库,纳入速效救心丸对比硝酸甘油治疗心绞痛急性发作的随机对照试验(RCT),检索时限均为建库至2019年10月30日。由两位评价者独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果纳入6项RCT,共651例心绞痛急性发作病人。Meta分析结果显示,试验组不良反应发生率低于对照组[RR=0.37,95%CI(0.20,0.69),P=0.002];两组心绞痛改善率[RR=1.00,95%CI(0.94,1.06),P=0.97]和心电图改善率[RR=0.94,95%CI(0.84,1.05),P=0.26]差异均无统计学意义。结论当前证据表明,舌下含服速效救心丸或硝酸甘油片在心绞痛急性发作的治疗方面疗效均较好,但速效救心丸不良反应更少,安全性好。     

参附强心丸治疗慢性心力衰竭的证据概述

目的系统评价参附强心丸联合西药常规治疗慢性心力衰竭的临床疗效及安全性,并进行证据评价。方法计算机检索中国期刊全文数据库、中文科技期刊全文数据库、万方数据库、中国生物医学文献数据库、EMbase、PubMed、the Cochrane Library,检索时间从数据库建库至2019年3月,搜集参附强心丸联合西药常规与西药常规治疗慢性心力衰竭的随机对照试验研究,按照纳入与排除标准筛选及纳入文献,提取病人一般资料、干预措施、观察指标及不良反应等信息,采用RevMan 5.3软件进行Meta分析,并采用GRADE系统对证据质量进行评估。结果共纳入5项研究,涉及421例病人。Meta分析结果显示,参附强心丸联合西药常规治疗心力衰竭可提高左室射血分数[WMD=4.39,95%CI(2.80,5.98),P<0.00001]、降低左室舒张末期内径[WMD=-2.79,95%CI(-3.67,-1.92),P<0.00001]、降低B型利钠肽(P<0.05)、提高6 min步行距离[WMD=40.62,95%CI(6.98,74.25),P=0.02]、改善明尼苏达心力衰竭生活质量量表积分[WMD=-6.83,95%CI(-8.76,-4.90),P<0.00001]、改善中医证候[RR=1.40,95%CI(1.18,1.66),P=0.0001],疗效均优于西药常规治疗,证据评级为低质量;可降低N末端B型脑钠肽前体[SMD=-0.71,95%CI(-0.92,-0.50),P<0.00001],疗效优于西药常规治疗,证据评级为中等质量。结论现有证据表明,参附强心丸联合西药常规治疗慢性心力衰竭可进一步改善病人症状和心功能,提高临床疗效,但临床证据质量偏低。     

Survey Results on Industry Practices and Challenges in Subgroup Analysis in Clinical Trials

This article provides a summary of the results of a recent survey in the pharmaceutical and device industry on the current practice and common issues in the identification and analysis of subgroups. The survey was part of a cross-industry effort sponsored by the Quantitative Sciences in the Pharmaceutical Industry (QSPI) for two purposes: (1) to identify general practices in how statistical subgroup analyses are planned and conducted in clinical trials and (2) collect information on similarities and differences across the prespecified types of subgroup analyses in terms of most common challenges, methodologies, and other characteristics. The survey results help integrate good practices and create a unifying framework for subgroup analyses in industry encompassing those in discovery/early phases directed to biomarkers identification and those at later stages for exploratory, confirmatory, or post hoc evaluations. Results from this survey identify the number one challenge to be the lack of power related to the sample size and number of subgroups tested. The findings further highlight an unmet need for intensified educational efforts focused on sharing statistical methodologies, experiences, and knowledge on the most appropriate approaches for identifying and analyzing subgroups. The scientific debate among industry, regulators and academia should continue to find solutions to unresolved challenges and perceived difficulties of subgroup analyses in clinical trials.     

Prospects for Electrical Performance Tuning in Ca3Co4O9 Materials by Metallic Fe and Ni Particles Additions

This work further explores the possibilities for designing the high-temperature electrical performance of the thermoelectric Ca₃Co₄O₉ phase, by a composite approach involving separate metallic iron and nickel particles additions, and by employing two different sintering schemes, capable to promote the controlled interactions between the components, encouraged by our recent promising results obtained for similar cobalt additions. Iron and nickel were chosen because of their similarities with cobalt. The maximum power factor value of around 200 μWm⁻¹K⁻² at 925 K was achieved for the composite with the nominal nickel content of 3% vol., processed via the two-step sintering cycle, which provides the highest densification from this work. The effectiveness of the proposed approach was shown to be strongly dependent on the processing conditions and added amounts of metallic particles. Although the conventional one-step approach results in Fe- and Ni-containing composites with the major content of the thermoelectric Ca₃Co₄O₉ phase, their electrical performance was found to be significantly lower than for the Co-containing analogue, due to the presence of less-conducting phases and excessive porosity. In contrast, the relatively high performance of the composite with a nominal nickel content of 3% vol. processed via a two-step approach is related to the specific microstructural features from this sample, including minimal porosity and the presence of the Ca₂Co₂O₅ phase, which partially compensate the complete decomposition of the Ca₃Co₄O₉ matrix. The obtained results demonstrate different pathways to tailor the phase composition of Ca₃Co₄O₉-based materials, with a corresponding impact on the thermoelectric performance, and highlight the necessity of more controllable approaches for the phase composition tuning, including lower amounts and different morphologies of the dispersed metallic phases.     

Development and delivery of the BOOST (Better Outcomes for Older adults with Spinal Trouble) intervention for older adults with neurogenic claudication

Neurogenic claudication due to spinal stenosis is a common cause of disability in older adults. Conservative treatments are a favourable treatment option. This paper describes the development and delivery of the BOOST (Better Outcomes for Older adults with Spinal Trouble) intervention, a physiotherapist-delivered physical and psychological intervention for the management of neurogenic claudication in older adults. The BOOST intervention is being tested in a multi-centre, randomised controlled trial in UK National Health Service Trusts; delivered by physiotherapists registered with the Health and Care Professionals Council. Participants are aged 65 years or older, registered with a primary care practice, and report symptoms consistent with neurogenic claudication. Intervention content and delivery was initially informed by clinical and patient experts, research evidence, and behaviour change guidelines; and refined following an intervention development day attended by researchers, health professionals, and Patient and Public Involvement representatives. The BOOST intervention comprises 12 group sessions, promoting sustained adherence with a long term home and physical activity programme. Each session includes education and group discussion, individually tailored exercises, and walking. Initial exercise levels are set at a one-to-one assessment. Continued home exercise adherence and increased physical activity following completion of the sessions is facilitated through support telephone calls.
Trial registration ISRCTN12698674.     

Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs

Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I–III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook.