Towards clinical data-driven eligibility criteria optimization for interventional COVID-19 clinical trials

ObjectiveThis research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data.Materials and MethodsOn June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020–June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death.ResultsThere were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4–28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event.DiscussionBy adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients.ConclusionsThis research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.     

The COVID-19 Trial Finder

Clinical trials are the gold standard for generating reliable medical evidence. The biggest bottleneck in clinical trials is recruitment. To facilitate recruitment, tools for patient search of relevant clinical trials have been developed, but users often suffer from information overload. With nearly 700 coronavirus disease 2019 (COVID-19) trials conducted in the United States as of August 2020, it is imperative to enable rapid recruitment to these studies. The COVID-19 Trial Finder was designed to facilitate patient-centered search of COVID-19 trials, first by location and radius distance from trial sites, and then by brief, dynamically generated medical questions to allow users to prescreen their eligibility for nearby COVID-19 trials with minimum human computer interaction. A simulation study using 20 publicly available patient case reports demonstrates its precision and effectiveness.     

我国COVID-19相关临床试验注册特点及存在的伦理学问题

目的：通过对我国新型冠状病毒感染(COVID-19)相关临床试验注册信息多角度分析,探讨其中存在的伦理学问题,以期为新突发传染病等公共卫生事件临床伦理的规范化提供依据。方法：在美国临床试验注册中心(ClinicalTrials.gov)和中国临床试验注册中心(ChiCTR)使用“新型冠状病毒”“COVID-19”等关键词检索2020年1月1日至2022年11月15日注册的COVID-19相关临床试验,归纳分析其注册的时空分布特点、研究类型、干预措施、研究状态及伦理等信息,发现并探讨相关伦理学问题。结果：共纳入1 560项COVID-19相关的临床试验,其中ClinicalTrials.gov注册481项,ChiCTR注册1 079项。临床试验注册高峰期集中在2020年2-4月;根据省级行政区划分湖北省、上海市、北京市临床试验注册量较多。干预性研究(843/1 560,54.00%)在所有注册类型中占比最高,注册内容涉及疫苗(202/843,23.96%)、化学药品(193/843,22.89%)、中医药(153/843,18.15%)及生物制品(90/843,10.68%)等多个方面;...     

新型冠状病毒肺炎知识图谱研究现状与展望

采用文献调研、定量统计与系统综述等方法,对新型冠状病毒肺炎知识图谱领域的代表性文献与应用项目进行全面梳理与总结,系统归纳新型冠状病毒肺炎知识图谱的领域分类、构建流程与实现技术,深入分析新型冠状病毒肺炎知识图谱在疫情防控、药物研发、辅助诊断、智能问答等关键领域的实际应用。在此基础上,针对现有研究的不足,从多模态知识图谱构建、跨语言知识融合、测评体系完善、图谱更新维护和深度应用5个方面展望了今后的研究方向。     

Misalignment between COVID-19 hotspots and clinical trial sites

Hundreds of interventional clinical trials have been launched in the United States to identify effective treatment strategies for combating the coronavirus disease 2019 (COVID-19) pandemic. However, to date, only a small fraction of these trials have completed enrollment, delaying the scientific investigation of COVID-19 and its treatment options. This study presents novel metrics to examine the geographic alignment between COVID-19 hotspots and interventional clinical trial sites and evaluate trial access over time during the evolving pandemic. Using temporal COVID-19 case data from USAFacts.org and trial data from ClinicalTrials.gov, U.S. counties were categorized based on their numbers of cases and trials. Our analysis suggests that alignment and access have worsened as the pandemic shifted over time. We recommend strategies and metrics to evaluate the alignment between cases and trials. Future studies are warranted to investigate the impact of the misalignment of cases and clinical trial sites on clinical trial recruitment.     

Clinical and epidemiological characteristics of COVID-19 mortality in Saudi Arabia

Objectives:To analyze the clinical and epidemiological characteristics for 224 of in-hospital coronavirus disease 2019 (COVID-19) mortality cases. This study’s clinical implications provide insight into the significant death indicators among COVID-19 patients and the outbreak burden on the healthcare system in the Kingdom of Saudi Arabia (KSA).Methods:A multi-center retrospective cross-sectional study conducted among all COVID-19 mortality cases admitted to 15 Armed Forces hospitals across KSA, from March to July 2020. Demographic data, clinical presentations, laboratory investigations, and complications of COVID-19 mortality cases were collected and analyzed.Results:The mean age was 69.66±14.68 years, and 142 (63.4%) of the cases were male. Overall, 30% of the COVID-19 mortalities occurred in the first 24 hours of hospital admission, while 50% occurred on day 10. The most prevalent comorbidities were diabetes mellitus (DM, 73.7%), followed by hypertension (HTN, 69.6%). Logistic regression for risk factors in all mortality cases revealed that direct mortality cases from COVID-19 were more likely to develop acute respiratory distress syndrome (odds ratio [OR]: 1.75, confidence intervel [CI: 0.89-3.43]; p=0.102) and acute kidney injury (OR: 1.01, CI: [0.54-1.90]; p=0.960).Conclusion:Aging, male gender and the high prevalence of the underlying diseases such as, DM and HTN were a significant death indicators among COVID-19 mortality cases in KSA. Increases in serum ferritin, procalcitonin, C-reactive protein (CRP), and D-dimer levels can be used as indicators of disease progression.     

新型冠状病毒肺炎治疗药物：磷酸氯喹

2019年新型冠状病毒肺炎（COVID-19）爆发以来,多种抗病毒药物先后试用于临床一线,我国《新型冠状病毒肺炎诊疗方案（试行第六版）》首次将磷酸氯喹纳入抗冠状病毒治疗的试用药物。作为抗击疟疾与风湿病的经典老药,磷酸氯喹在临床已应用80余年,而其在各种抗病毒治疗中,也表现出良好的效果。在COVID-19治疗中,氯喹在体内外均表现出抗病毒作用,个别临床研究的初步结果表明,其效果可能优于洛匹那韦/利托那韦。氯喹主要通过在寄生虫食物泡内和细胞溶酶体中积聚,提高其pH值而发挥抗寄生虫和抗病毒作用。在COVID-19的治疗中氯喹可能影响血管紧张素转化酶-2（ACE2）的糖基化,而抑制SARS-CoV-2表面的S蛋白与ACE2受体结合进入宿主细胞。在氯喹长年的临床应用中,发现其药代动力学特征表现也较为特异,半衰期长（2.5 d~10 d）,表观分布容积巨大,在肝、脾、肾、肺中的浓度高于血浆浓度达200~700倍,而其在全血、血浆和血清中浓度也存在较大的差异,不同种族和个体间亦是如此。因此,氯喹稳态血药浓度范围与疗效间的关系目前尚不明确。氯喹毒性主要与超剂量使用相关,而且治疗剂量与毒性剂量和致死剂量十分接近。一般认为,氯喹单次剂量（基质）超过20 mg/kg就会有毒性,而超过30 mg/kg就能致死。因此,本文就磷酸氯喹在COVID-19治疗中的一些研究现状,及其药代动力学特点,抗病毒治疗与机制,以及氯喹的安全性作一综述。     

Outcomes of tracheostomy in COVID-19 patients in National Guard Health Affairs,Riyadh, Saudi Arabia

Objectives:To evaluate coronavirus disease 2019 (COVID-19) patient tracheostomy outcomes.Methods:All COVID-19 patients at the National Guard Hospital, Riyadh, Saudi Arabia, were retrospectively recruited. Those who had tracheostomies between April and December 2020 were included.Results:The population was 45 patients, of which 30 (66.7%) were males, 15 (33.3%) were females and the mean age was 66.76±12.74 years. The tracheostomy indications were anticipated prolonged weaning in 40 (88.9%) and failed extubation in 5 (11.1%) of the patients. The mean intubation to tracheostomy duration was 20.62±7.21 days. Mortalities were high, with most attributed to COVID-19. Mortality and a pre-tracheostomy C-reactive protein (CRP) uptrend were significantly related (p=0.039). Mortality and intubation to tracheostomy duration were not significantly related. The mean post-tracheostomy time to death was 10.64±6.9 days. Among the survivors, 20 (44.4%) males and 11 (24.4%) females were weaned off mechanical ventilation; 9 (20%) remained on ventilation during the study. The mean ventilation weaning time was 27.92±20 days.Conclusion:The high mortality rate was attributed to COVID-19. Mortality and a pre-tracheostomy CRP uptrend were significantly related; uptrend patients experienced far more mortalities than downtrend patients. Unlike previous findings, mortality and intubation to tracheostomy duration were not significantly related.     

The emerging role of clinical informatics fellows in service learning during the COVID-19 pandemic

ObjectiveThe study sought to describe the contributions of clinical informatics (CI) fellows to their institutions’ coronavirus disease 2019 (COVID-19) response.Materials and MethodsWe designed a survey to capture key domains of health informatics and perceptions regarding fellows’ application of their CI skills. We also conducted detailed interviews with select fellows and described their specific projects in a brief case series.ResultsForty-one of the 99 CI fellows responded to our survey. Seventy-five percent agreed that they were “able to apply clinical informatics training and interest to the COVID-19 response.” The most common project types were telemedicine (63%), reporting and analytics (49%), and electronic health record builds and governance (32%). Telehealth projects included training providers on existing telehealth tools, building entirely new virtual clinics for video triage of COVID-19 patients, and pioneering workflows and implementation of brand-new emergency department and inpatient video visit types. Analytics projects included reports and dashboards for institutional leadership, as well as developing digital contact tracing tools. For electronic health record builds, fellows directly contributed to note templates with embedded screening and testing guidance, adding COVID-19 tests to order sets, and validating clinical triage workflows.DiscussionFellows were engaged in projects that span the breadth of the CI specialty and were able to make system-wide contributions in line with their educational milestones.ConclusionsCI fellows contributed meaningfully and rapidly to their institutions’ response to the COVID-19 pandemic.     

Challenges in diabetic foot treatment during pandemic of COVID-19

Objectives:To avoid hospital spread of Coronavirus-2019 (COVID-19) and to analyze out of hospital outcomes after amputation.Methods:Prospective analysis of data obtained from 60 diabetic patients in 2020 was performed at Cantonal Hospital Zenica, Zenica, Bosnia and Herzegovina. Personal protection equipment included double surgical mask, glasses, disposable surgical coats, and surgical masks for patients. Swabs were used to take samples from wounds. We randomly divided patients in 2 groups of 30 patients each. In pre-operative treatment, we used local anesthesia lidocaine hydrochloride 2% (Belupo, Koprivnica, Croatia) in group A and systemic analgesia intravenous tramadol chloride 100 mg intravenous (Krka, Novo Mesto, Slovenia) in group B. Wounds were surgically treated each day and heal spontaneously. Periodical control exams were performed.Results:Wound healing did not present any statistically significant differences between groups (group A: 69±21.97 and B: 61±22.13 days, t=−1.22; p=0.11). No statistically significant differences (p<0.05) between groups A and B in wound healing regarding to gender or cigarette use was noted.Conclusion:No significant differences in amputation treatment between the 2 comparative groups were noted. No confirmed COVID-19 infections in medical staff who performed surgical interventions or in treated patients were detected.     

COVID-19 in children ranging from asymptomatic to a multi-system inflammatory disease: A single-center study

Objectives:To identify clinical and laboratory characteristics of the Saudi children with confirmed COVID-19.Methods:Eighty-eight children (0-14 years) with COVID-19 who were admitted to Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia from April to June 2020 were recruited.Results:Mean age was 5.74 ± 4.7 years with 41 (49.4%) males and 42 (50.6%) females. The length of hospital stay (LOS) ranged from 1 to 17 days. The main source of infection was infected family members. Mean values of C-reactive protein (CRP), serum ferritin, and lactate dehydrogenase (LDH) were noticeably above normal. Degree of severity and length of stay was significantly correlated with lymphopenia (r= -0.36; p=0.001), whereas it was positively correlated with absolute neutrophil count and with high inflammatory markers, such as CRP, LDH, and others.Conclusions:Identifying the clinical and laboratory characteristics of the Saudi children with confirmed COVID-19 will improve understanding of this disease’s presentation and will help put rapid and proper management strategies into place to face this pandemic. A high index of suspicion is needed for cases presenting with multi-system inflammatory disease, which represented 5.7% of the included study population.     

Evaluation of COVID-19 myths in Saudi Arabia

Objectives:To examine the awareness level of COVID-19 and to highlight the frequency of myths and misconceptions among Saudi Arabia’s population.Methods:We conducted a cross-sectional study from June 13 to 20, 2020 by distributing a 16-item online Google forms questionnaire among adults (18-65 years old) living in Saudi Arabia. We utilized the convenience sampling. Data analysis was performed using Chi-square and multiple regression analysis on Jamovi.Results:A total of 1436 responses were analyzed with 43.5% males and 56.5% females. Most respondents (89.1%) thought that only the elderly above 60 years old are considered at high risk of contracting COVID-19. Most respondents (86.5%) agreed that people with other health conditions could be more affected by COVID-19. Approximately 97.2% agreed that wearing a mask and avoiding touching eyes, nose, and mouth with unwashed hands was the leading preventive action. Most participants (99.4%) chose fever as an associated symptom. Respondents from the healthcare sector presented statistically higher scores than those in non-healthcare sectors (p<0.001). Higher education and higher salary were important predictors of better COVID-19 knowledge.Conclusion:Public health officials need to increase awareness measures on COVID-19 to limit myths and misconceptions and reduce psychological distress associated with it.     

中国MSC临床试验注册阶段性特征调查分析

目的 基于中国临床试验注册中心平台，分析探讨间充质干细胞（mesenchymal stem cell，MSC）临床试验研究在我国的特点及发展趋势。方法 通过在中国临床试验注册中心数据库进行检索，将2007年建库起至2022年4月的所有与MSC相关的临床试验项目纳入统计，对项目名称、研究所涉疾病/系统、研究所处阶段、注册时间、注册状态、研究负责单位地域分布等信息进行整理分析。结果 共有197项MSC相关临床试验纳入统计，注册数量整体呈逐年增加趋势；注册地集中在北京、上海、广东等地；经费以医院资助、地方财政、国家财政资金为主；项目研究以脐带为间充质干细胞主要来源，共涉及11个类别的系统相关疾病。结论 现阶段，MSC临床试验数目呈递增趋势，但存在地区间的不均衡性；我国干细胞研究者的临床试验注册观念正逐步建立，且已意识到临床注册的重要性，未来将持续促进MSC治疗的规范化和临床应用转化。     

基于新型冠状病毒肺炎的临床数据治理和科研平台建设实践

我院作为新型冠状病毒肺炎患者收治的定点医院,积累了大量新型冠状病毒肺炎患者的医疗数据。为有效利用这些数据为临床关于新型冠状病毒肺炎科研攻关服务,我院自主研发基于新型冠状病毒肺炎的科研数据平台。利用ETL工具KETTLE整合新型冠状病毒肺炎患者的门诊和住院数据,跨平台采集和清洗HIS、电子病历、LIS和PACS等业务系统的数据,形成新型冠状病毒肺炎专病库。以多种数据关联查询以及统计分析为设计思路的科研平台,为临床医生探索性研究提供思路以及数据支撑,进一步提高了临床关于新型冠状病毒肺炎科研产出的速度和质量。     

Clinical characteristics and outcomes of children with COVID-19 in Saudi Arabia

Objectives:To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection.Methods:In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.Results:Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died.Conclusion:All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.     

Could flank pain be an indicator of COVID-19 infection?

BackgroundWe describe the incidental detection of patients infiltrates due to COVID-19 in lung basal sections in patients undergoing abdominal computed tomography (CT) with flank pain attending the urology outpatient clinic during the current pandemic.MethodsWe retrospectively analysed 276 patients admitted to the Siirt Training and Research Hospital Urology outpatients clinic between 15 March 2020 and 9 August 2020 with a complaint of flank pain and undergoing non-contrast abdominal CT. A total of 10 patients with COVID-19 compatible findings in CT were defined as the study group. A control group was formed from 10 patients with only urological pathologies (kidney stones, ureteral stones, and hydronephrosis) without a COVID-19 compatible appearance on CT.ResultsTen (3.6 %) patients were identified with COVID-19 and pneumonic infiltrations in the basal regions of the lungs; diagnosis was made by cross-sectional abdominal CT. The visual analog scale (VAS) score of flank pain was significantly higher in the control group (p<0.001); these subjects had urological pathology and no evidence of COVID-19 in the basal regions of the lungs on abdominal CT. There were no signs of COVID-19 disease detected during the admissions procedure in the urology outpatient clinic, including fever, cough, and shortness of breath.ConclusionDuring the COVID-19 pandemic, it is important to consider a diagnosis of COVID_19 in patients reporting non-severe flank pain if no urological pathology is evident on abdominal CT scans.     

The infodemics of COVID-19 amongst healthcare professionals in India

BackgroundThere is a deluge of information and misinformation about COVID-19. The present survey was conducted to explore the sources of information /misinformation for healthcare professionals from India.MethodsA cross-sectional online survey using snowballing technique was conducted from 24 Mar to 10 Apr 2020. The questionnaire was pretested and developed using standard techniques. It was circulated among medical students and physicians. Data were analysed using the STATA software.ResultsData of 758 participants were analysed. A total of 255 (33.6%) medical students, 335 (44.2%) nonspecialists and 168 (22.1%) specialists participated. The most common source of formal and informal information was official government websites and online news, respectively. A total of 517 (68.2%) participants accepted receiving misinformation. Social media and family and friends were the most common sources of misinformation. Seventy-two percent of participants agreed that spread of information helped to contain COVID-19, but more than that 75% agreed to having received inaccurate information. Seventy-four percent of respondents felt the need for regulation of information during such times; 26% and 33% felt that information about COVID-19 made them feel uncomfortable and distracts routine decision-making, respectively, and 50% felt it was difficult to differentiate correct from incorrect information about COVID-19.ConclusionThe study explored the sources of information and misinformation and found a high prevalence of misinformation, especially from social media. We suggest the need to better manage the flow of information so that it can be an effective weapon against SARS-CoV2. There is a need for doctors to adapt to the changing times of infodemics accompanying pandemics.     

Dynamics of social corrections to peers sharing COVID-19 misinformation on WhatsApp in Brazil

ObjectiveOnline COVID-19 misinformation is a serious concern in Brazil, home to the second-largest WhatsApp user base and the second-highest number of COVID-19 deaths. We examined the extent to which WhatsApp users might be willing to correct their peers who might share COVID-19 misinformation.Materials and MethodsWe conducted a cross-sectional online survey using Qualtrics among 726 Brazilian adults to identify the types of social correction behaviors (SCBs) and health and technological factors that shape the performance of these behaviors.ResultsBrazil’s WhatsApp users expressed medium to high levels of willingness to engage in SCBs. We discovered 3 modes of SCBs: correction to the group, correction to the sender only, and passive or no correction. WhatsApp users with lower levels of educational attainment and from younger age groups were less inclined to provide corrections. Lastly, the perceived severity of COVID-19 and the ability to critically evaluate a message were positively associated with providing corrections to either the group or the sender.DiscussionThe demographic analyses point to the need to strengthen information literacy among population groups that are younger with lower levels of educational attainment. These efforts could facilitate individual-level contributions to the global fight against misinformation by the World Health Organization in collaboration with member states, social media companies, and civil society.ConclusionOur study suggests that Brazil’s WhatsApp users might be willing to actively respond with feedback when exposed to COVID-19 misinformation by their peers on small-world networks like WhatsApp groups.