新冠肺炎诊疗关键要点总结

2019年12月至今,我国武汉爆发的新型冠状病毒肺炎(简称新冠肺炎,COVID-19)疫情引起了全球关注,新型冠状病毒对人具有很强的感染能力,具有人际传播特点,主要以飞沫传播、直接接触为主,人群普遍易感。新冠肺炎以发热、乏力、干咳为主要临床症状,重症患者可并发急性呼吸窘迫综合征、脓毒性休克、凝血功能障碍及多器官功能衰竭等。实验室检查表现为外周血白细胞计数正常或降低、淋巴细胞计数减低。胸部HRCT表现为双肺多发磨玻璃样影,以胸膜下分布为著,可出现肺实变、支气管充气征。根据病变范围将HRCT表现分为早期、进展期、重症期及吸收期。在新冠肺炎治疗方面,目前尚无特异性抗病毒治疗药物,多以最佳支持治疗为主。目前研究证实,可能有效的抗病毒药物包括瑞德西韦、洛匹那韦/利托那韦、恢复期血浆及单克隆抗体等,但仍需临床试验验证。     

遂宁地区首发9例新型冠状病毒感染肺炎患者的救治分析

目的分析四川省遂宁地区首发9例新型冠状病毒肺炎患者的临床特征及救治特点,为新型冠状病毒肺炎的合理防治提供借鉴。方法回顾性分析2020年1～2月收治的9例新型冠状病毒肺炎患者的临床资料。结果 9例患者中,男3例,女6例,年龄24～35岁。发病初期大多有发热、咳嗽等症状,有1例患者以腹痛为首发症状,仅有1例患者无任何临床症状。患者初期血常规提示白细胞计数(WBC)正常,淋巴细胞值有降低,且大多有肌酶谱的轻度异常; 9例患者均有胸部CT异常。入院后均予以洛匹那韦/利托那韦抗病毒治疗,最终全部康复出院。结论新型冠状病毒肺炎患者早期临床表现不典型,但均有肺部影像学典型表现,早期发现、早期诊断、早期予以抗病毒治疗是救治成功的关键。     

全球药物干预治疗高血压合并其他疾病指南的系统评价

目的系统评价药物干预高血压合并不同疾病指南。方法计算机检索MEDLINE、EMbase、CBM、WanFang Data、NGC(national guideline clearinghouse)、GIN(guideline international netword)、NICE(national institute for health and clinical excellence)及中国临床指南协作网(CPGN)等中、英文数据库和指南网站,纳入药物干预高血压合并其他疾病的临床指南,采用指南评价工具(appraisal of guidelines for research and evaluation,AGREE)评价指南的方法学质量,通过同类比较,分析不同地区和质量疾病的指南对药物推荐的异同及特点。结果共纳入21篇药物干预高血压合并其他疾病的指南。其中高血压合并冠心病、卒中、糖尿病及肾病的指南分别有5、5、7及4篇,发布于2000～2011年。其中A级指南0篇,B级19篇,C级2篇和循证指南9篇。4类指南均在"制定指南的参与人员"及"适用性"2个领域的平均得分欠佳。循证指南中的证据级别和推荐强度级数的分类方法各有4和3种,表达形式各有10和6种。对高血压伴心绞痛患者,指南一致推荐β受体阻滞剂(β-blocker,BB)和CCB;对高血压伴心梗患者,指南一致推荐ACEI和BB;对高血压伴心衰患者,ACEI、血管紧张素受体拮抗剂(angiotensin-receptor blocker,ARB)及BB是指南一致推荐药物。对高血压卒中后期患者,76.47%的指南推荐D和ACEI。对急性脑卒中的血压控制,指南推荐内容主要基于美国相关专业委员会制定的指南。对高血压合并糖尿病或肾病患者,收缩压/舒张压控制范围一致推荐应分别小于130/80 mmHg。对高血压合并糖尿病患者,一致推荐ACEI,其次为D和CCB;对高血压合并肾病患者,一致推荐ACEI/ARB。5篇推荐使用CCB的指南中有3篇来自亚洲。结论高血压合并不同疾病的指南中循证指南占比较高,但方法学质量存在差异。循证指南中对证据级别和推荐强度的划分标准不一,有待进一步完善。对高血压合并冠心病、糖尿病、肾病及卒中后期患者,临床证据充分且结果具有一致性,指南推荐内容基本一致,且无地区和质量级别差异。对目前临床研究尚未达成共识的疾病,临床推荐药物存在差异。目前对高血压合并急性卒中患者的血压管理暂无定论。     

抗新型冠状病毒感染药物经济学评价的系统评价

目的 系统评价国内外抗新型冠状病毒感染药物的经济评价研究,为临床合理用药提供参考。方法 计算机检索PubMed、Cochrane Library、EMbase、Web of Science、INAHTA、SinoMed、WanFang Data、CNKI数据库,检索时限为2020年1月1日—2023年3月25日,搜集抗新型冠状病毒感染药物经济学评价研究。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,进行描述性分析。结果 共纳入22篇文献,其中11个研究采用卫生体系角度,多数研究的成本类型为直接医疗成本。纳入研究质量评价总体符合率为42%～70%,存在模型设定不全、不确定性分析不全面,缺乏利益相关方参与等不足。研究结果显示免疫治疗药物（地塞米松、托珠单抗）、中和抗体药物（REGEN-COV抗体）、小分子药物（巴瑞替尼、奈玛特韦/利托那韦、莫奈匹韦、法匹拉韦）和他汀类药物治疗新冠患者具有成本-效果,但对瑞德西韦的经济性评价结果存在一定的差异。结论 目前有关抗新型冠状病毒感染药物的经济学评价研究相对较少,但显示新冠防治的多数药物干预措施具有成本-效果。建议未来开展更多规范的、...     

糖尿病足风险筛查的最佳证据总结

目的检索、评价和整合糖尿病患者糖尿病足风险筛查的最佳证据。方法应用循证护理方法检索国内外相关数据库和专业网站中有关糖尿病足风险筛查的所有指南、证据总结、最佳实践信息册、推荐实践、系统评价、专家共识等。结果共纳入文献17篇,包括临床决策1篇、指南9篇、系统评价3篇、临床推荐2篇、专家共识2篇,最终形成16条最佳证据,包括筛查人员、筛查对象与时机、筛查内容与方法、风险分级与管理4大类。结论总结了糖尿病患者糖尿病足风险筛查的最佳证据,为医务工作者在临床工作中为糖尿病患者进行足部风险筛查提供了循证依据。     

妊娠期糖尿病临床护理实践指南的更新

目的对课题组2018年构建的妊娠期糖尿病临床护理实践指南进行更新和补充。方法系统检索国内外专业网站及数据库关于妊娠期糖尿病临床护理的最新证据;由2名研究员对文献质量进行独立评价,对纳入的文献进行资料提取和证据汇总,并采用Delphi法,通过专家咨询达成推荐意见及推荐强度。结果共纳入7篇指南和49篇系统评价;结合专业人员的判断,总结出14条妊娠期糖尿病患者筛查及管理的相关证据,包括疾病筛查和诊断、饮食干预、运动干预、血糖监测和产后复查等方面。经过专家共识,确定7条强推荐,7条弱推荐。结论本研究总结了目前关于妊娠期糖尿病患者筛查及管理的最新最佳证据,对原有的妊娠期糖尿病临床护理实践指南进行了更新,可为临床护理人员提供基于证据的决策建议和依据,促进妊娠期糖尿病的规范化管理。     

高血压系列问答(10)如何理解JNC-7中列举的降压药物强适应证?

美国高血压预防与治疗指南(JNC-7)中对6种临床情况合并存在高血压时如何选择降压药物,提出了建议,即强适应证. 这六种情况包括:糖尿病、心力衰竭、脑卒中后、冠心病高危人群、心肌梗死后和慢性肾脏疾病.     

注射用阿奇霉素与注射用更昔洛韦存在配伍禁忌

我们经过临床应用与实验发现注射用阿奇霉素与注射用更昔洛韦之间存在着配伍禁忌,查阅《400种注射剂临床配伍应用检索表》、《药理学》、《中国医师药师临床用药指南》均未记录上述2种药物存在配伍禁忌。注射用阿奇霉素说明书述与氨茶碱、华法林、卡马西平、地高辛合用时应注意监测血药浓度和     

更昔洛韦-纤维蛋白胶-羊膜复合物的缓释特性

背景:近年来,纤维蛋白胶作为药物缓释载体的作用日益受到人们的重视。更昔洛韦是一种有效治疗病毒性角膜炎的广谱抗病毒药物。故选择此药物进行胶联羊膜缓释药膜的初步探索。目的:观察更昔洛韦-纤维蛋白胶-羊膜复合物的缓释特性,探索临床治疗病毒性角膜炎的新方法。方法:体外实验:将纤维蛋白胶与更昔洛韦混合后与羊膜黏合,制成更昔洛韦-纤维蛋白胶-羊膜复合物,观察更昔洛韦的体外缓释情况。体内实验:新西兰大白兔右眼为实验组在兔眼表作更昔洛韦-纤维蛋白胶-羊膜移植;左眼为对照组滴1g/L更昔洛韦眼液,每2h滴100μL。应用高效液相色谱法测试不同时间点房水中更昔洛韦的质量浓度。结果与结论:体外释放实验显示,24h后更昔洛韦的累计释放率为(45.67±5.32)%,48h后为(63.42±4.68)%,96h后释放趋于平衡。动物实验表明:实验组房水中更昔洛韦浓度随时间逐渐降低。第1天时,实验组房水药物浓度显著高于对照组(P<0.01)。第2,3天,实验组房水更昔洛韦质量浓度稍高,与对照组比较差异无显著性意义。第4,5天,实验组房水药物浓度低于对照组(P<0.05)。结果提示,在体外及体内条件下,更昔洛韦-纤维蛋白胶-羊膜复合物均具有良好的缓释特性,可望成为治疗病毒性角膜炎的新手段。     

肝移植术后巨细胞病毒感染的诊断与防治--附150例报告

目的:探讨肝移植术后患者巨细胞病毒(cytomegalovirus,CMV)感染的诊治方法.方法:回顾性分析150例成人肝移植病例的临床资料.结果:移植术后即开始静脉使用更昔洛韦,连续2周以预防CMV感染.预防用药2周后检测外周血白细胞中CMV抗原,CMV抗原超过5/50 000白细胞为CMV感染阳性,CMV抗原阳性21例(14.0%,21/150),其中20例(95.2%)表现为无症状CMV感染,1例表现为CMV肺炎.对12例CMV抗原超过5/50 000白细胞但少于15/50 000白细胞者予口服阿昔洛韦治疗,9例CMV抗原超过15/50 000白细胞者予静脉使用更昔洛韦治疗.经治疗后患者的血清CMV抗原全部转阴,1例CMV肺炎死于呼吸衰竭.结论:外周血CMV抗原检测是诊断CMV感染的一项准确指标,可以指导防治CMV疾病用药,术后静脉使用更昔洛韦可以有效预防CMV感染的发生.     

Anti-HIV drug repurposing against SARS-CoV-2

A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health. However, no approved drugs have been found to effectively inhibit the virus. Since it has been reported that HIV protease inhibitors can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose six approved anti-HIV drugs and investigated their binding interactions with 3CLpro to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection. The molecular docking results indicate that the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than does SARS-CoV-1. Two docking complexes (indinavir and darunavir) with high docking scores were further subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two protease inhibitors and SARS HCoV 3CLpro. Our results show that, among the inhibitors tested, darunavir has the highest binding affinity with SARS-CoV-2 and SARS-CoV-1 3CLpro, indicating that it may have the potential to be used as an anti-COVID-19 clinical drug. The mechanism behind the increased binding affinity of HIV protease inhibitors toward SARS-CoV-2 3CLpro (as compared to SARS-CoV-1) was investigated by MD simulations. Our study provides insight into the possible role of structural flexibility during interactions between SARS HCoV 3CLpro and inhibitors and sheds light on structure-based design of anti-COVID-19 drugs targeting SARS-CoV-2 3CLpro.

A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health.     

A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19

PurposeCOVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19.MethodsPubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19.ResultsWe included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro.ConclusionsThere is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.     

Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.     

COVID-19 and gastroenteric manifestations

Coronavirus disease 2019 (COVID-19), caused by the infection of a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], has become a pandemic. The infection has resulted in about one hundred million COVID-19 cases and millions of deaths. Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system, it also attacks the gastrointestinal epithelial cells through the same receptor, angiotensin converting enzyme 2 receptor, which results in gastroenteric symptoms and potential fecal-oral transmission. Besides the infection of SARS-CoV-2, the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs. In this review, we update the clinical features, basic studies, and clinical practices of COVID-19-associated gastroenteric manifestations.     

Kaletra (lopinavir/ritonavir)

OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, efficacy, safety, and clinical use of lopinavir/ritonavir (Kaletra, Abbott Laboratories). DATA SOURCES: English-language MEDLINE and AIDSline searches were performed (1966-July 2001) using lopinavir, ABT-378, and Kaletra as key words. Abstracts from infectious diseases and HIV scientific meetings were identified. Abbott Laboratories provided additional published and unpublished information. DATA EXTRACTION: All publications, meeting abstracts, and unpublished information were reviewed and relevant items included. In vitro and preclinical studies were included as well as Phase II and III clinical trials. DATA SYNTHESIS: Lopinavir/ritonavir is a fixed-dose protease inhibitor (PI) combination used for the treatment of HIV-1 infection. Lopinavir, the active component of this combination, is extensively metabolized by CYP3A4 and produces low systemic concentrations when used alone. Ritonavir potently inhibits CYP3A4 and is used to enhance the systemic exposure of lopinavir. This combination results in lopinavir concentrations that greatly exceed those necessary in vitro to inhibit both wild-type and PI-resistant HIV isolates. In clinical trials with antiretroviral na?ve and experienced patients, lopinavir/ritonavir was effective at suppressing HIV-RNA and increasing CD4+ T cell counts. Compared with other PIs, lopinavir/ritonavir may have advantages in the areas of pharmacokinetics, efficacy, and resistance. Toxicity, drug interactions, and medication adherence are important considerations surrounding its clinical use. CONCLUSIONS: Lopinavir/ritonavir is an effective option for the treatment of HIV-1-infected individuals when used in combination with other antiretroviral agents. It may be used as a component of initial therapy or salvage therapy; future studies will better define its place in therapy.     

新型冠状病毒肺炎合并心血管疾病的临床治疗观察

目的 探讨新型冠状病毒肺炎(COVID-19)合并心血管疾病患者治疗措施.方法 收集155例COVID-19患者临床资料,分析155例患者治疗用药情况,并对21例合并心血管疾病患者临床治疗进行分析.结果COVID-19合并心血管疾病单中心发病率13.5％,其中高血压患者较多(95.2％),老年COVID-19患者合并心...     

Will plant-made biopharmaceuticals play a role in the fight against COVID-19?

ABSTRACT

Given the dramatic impact of the COVID-19 pandemic, it is imperative to divulge all the available technologies with the potential to fight against this virus. Plant biotechnology offers potential solutions to this pandemic through the development of low-cost vaccines and antibodies useful for therapy, prophylaxis, and diagnosis. The technology to produce plant-made biopharmaceuticals is already established; two examples of these are: a therapeutic enzyme that has entered the market and the influenza vaccines that are currently under clinical trials with encouraging results. Thus far, some companies have started developing anti-COVID-19 antibodies and vaccines. In particular, plant-made antibodies might be timely produced and approved for human use in the short term, while the development of vaccines will take longer time (clinical evaluations could be concluded by the end of 2021); nonetheless, the candidates obtained will be valuable tools for future outbreaks. The key aspects that will define the exploitation of this technology in the fight against COVID-19 are discussed.     

Presentation and outcome of myocardial infarction with non-obstructive coronary arteries in coronavirus disease 2019

Among the cardiac complications of coronavirus disease 2019 (COVID-19), one increasingly reported in the literature is myocardial infarction with non-obstructive coronaries (MINOCA). We reviewed all reported cases of MINOCA in COVID-19 patients to summarize its clinical features, evaluation, and treatment. We performed a literature search in Pubmed using the search terms ‘COVID-19’ and ‘MINOCA’ or ‘non-obstructive coronaries’. Among the reported cases, the mean age was 61.5 years (SD ± 13.4), and 50% were men. Chest pain was the presenting symptom in five patients (62.5%), and hypertension was the most common comorbidity (62.5%). ST-elevation was seen in most patients (87.5%), and the overall mortality rate was 37.5%. MINOCA in COVID-19 is an entity with a broad differential diagnosis. Therefore, a uniform algorithm is needed in its evaluation to ensure timely diagnosis and management.     

Potential drug–drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug–drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.     

Convalescent (immune) plasma treatment in a myelodysplastic COVID-19 patient with disseminated tuberculosis

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.