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。     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.     

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.     

Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial

Background:Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer.Methods:This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software.Discussion:This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer.Trial registration:OSF Registration number: D DOI 10.17605/OSF.IO/QHW86     

Effect of Day Optimizing Throughput (Dot) Knee Software Implementation on Magnetic Resonance Imaging Workflow Efficiency

PurposeAttempts by magnetic resonance (MR) manufacturers to help imaging centres improve patient throughput has led to the development of more automated acquisition. This software is capable of customizing individual scan alignment; potentially improving imaging efficiency and standardizing protocols. However, substantial investments are required to introduce such systems, potentially deterring their widespread application. This study assessed the implementation costs and reduction in examination durations for automated knee MR imaging (MRI) software.Materials and MethodsResearch activities were performed at a community-based academic centre on a 3-Tesla (3-T) system using Siemens' Day Optimizing Throughput (Dot) knee software. Examination acquisition times were extracted from the system before and after software implementation. Fiscal year 2012/13 finances were used to determine the average hourly cost of MRI utilization. Costs associated with automated software implementation were also calculated. Finally, the number of knee scans required to achieve a positive return on investment using the software was established.Results and DiscussionThe mean (standard deviation, sample size) pre- and post-Dot software scan times were 23.20 (4.18, n = 266) and 21.94 (4.51, n = 59) minutes, respectively, for a routine knee scan and 11.88 (1.60, n = 74) and 11.24 (1.51, n = 27) minutes, respectively, for a fast knee scan. The overall weighted average resulted in a 64-second time savings per automated knee examination. This negligible time savings would be extremely difficult to make use of clinically. Dot simplified 29 unique knee protocols to two, improving the consistency of knee examinations. Current Dot software is not compatible with all patients and therefore has limitations that are a concern among MR technologists.ConclusionAdoption of automated knee systems could assist in standardizing protocols; however, the cost of implementation and difficulty in modifying patient scheduling to reflect the minimal time savings would make a financial return unlikely to occur at small- and medium-sized institutions.     

使用棱镜重新定位双侧中心暗点患者视网膜物像的预试验

目的 本研究使用激光扫描检眼镜(SLO)评价双侧中央暗点患者使用棱镜后的眼球运动反应.方法 本预试验共招募6例有双侧中央暗点的年龄相关性黄斑变性(AMD)患者以及6例正常视力的志愿者.首先用Nidek MP-1微视野仪确认患者的中央暗点和优选视网膜注视点(PRL),然后用Rodenstock SLO,在将视标投射在优选视网膜注视点时拍下实时视网膜像,接着在受检者眼前加入6～8 PD的棱镜,要求受检者保持注视视标,这时通过视网膜标记来测量视网膜像的移位量,以及随后发生的优选视网膜注视点的再次注视.过程中平均移位量和再次注视时间通过图像软件(ImageJ software)来计算.结果 实验组再次注视时的移位量在3个像素点或11.66个弧分之内(x轴:2.90±3.92,y轴:2.53±4.18).对照组再次注视时的移位会准确些(x轴:0.33±1.15,y轴:0.89±2.50),但与实验组差异无统计学意义(tx=1.32,Px＞0.05;ty=0.80,Py＞0.05).对照组再次注视时间(0.98±0.19)s较实验组(2.83±1.63)s要短,差距有统计学意义(t=5.03,P＜0.01).其中有1例实验组受检者没有发生再次注视,其结果被排除并单独分析.结论 研究发现,双眼中央暗点患者对棱镜物像转移后的再注视反应与正常人接近,但实验组再注视明显较对照组慢,并有1例受检者没有发生再注视.该数据说明双侧中央暗点患者无论眼前有没有棱镜,都会利用相同的视网膜位置视物,因此,通过棱镜物像再定位的意义不大.