Change in disease burden associated with influenza and air pollutants during the COVID-19 pandemic in Hong Kong.

Objectives: This study aimed to estimate the variation in disease burden associated with air pollutants and other respiratory viruses during the COVID-19 pandemic. Methods: We adopted a machine learning approach to calculate the excess mortality attributable to air pollutants and influenza, during the pre-pandemic and pandemic period. Results: In the first 2 years of the COVID-19 pandemic, there were 8762 (95% confidence interval, 7503-9993), and 12,496 (11,718-13,332) excess all-cause deaths in Hong Kong. These figures correspond to 117.4 and 167.9 per 100,000 population, and 12.6% and 8.5% of total deaths in 2020 and 2021, respectively. Compared to the period before the pandemic, excess deaths from all-causes, cardiovascular and respiratory diseases, pneumonia and influenza attributable to influenza A and B significantly decreased in all age groups. However, excess deaths associated with ozone increased in all age-disease categories, while the relative change of nitrogen dioxide (NO2) and particular matters less than 10 µm (PM10) associated burden showed a varied pattern. Conclusions: A notable shift in disease burden attributable to influenza and air pollutants was observed in the pandemic period, suggesting that both direct and indirect impacts shall be considered when assessing the global and regional burden of the COVID-19 pandemic.

Hand Hygiene Education Components Among First-Year Nursing Students: A Cluster Randomized Clinical Trial.

Importance: Few studies have directly and objectively measured the individual and combined effects of multifaceted hand hygiene education programs. Objective: To evaluate the individual and combined immediate effects of an instructional video and hand scan images on handwashing quality, decontamination, and knowledge improvement. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in June to July 2023 among first-year nursing students at a university in Hong Kong. The study used an intention-to-treat analysis. Intervention: Hand hygiene education sessions featuring an instructional video, hand scan images, or both. Main Outcomes and Measures: The primary outcome was the change in residue from fluorescent lotion remaining on participants' hands after handwashing before and after the intervention. The secondary outcomes included handwashing quality and knowledge of hand hygiene. Results: A total of 270 of 280 students (mean [SD] age, 19 [1] years; 182 [67.4%] female) participated in the trial (96.4% participation rate). Participants were randomized to a control group (66 participants), hand scan image group (68 participants), instructional video group (67 participants), and hand scan image with instructional video group (69 participants). All intervention groups had greater reductions in residue after the intervention compared with the control group, although none reached statistical significance (hand scan image group: 3.9 [95% CI, 2.0-5.8] percentage points; instructional video group: 4.8 [95% CI, 2.9-6.7] percentage points; hand scan image with instructional video: 3.5 [95% CI, 1.6-5.4] percentage points; control group: 3.2 [95% CI, 1.3-5.2] percentage points). The instructional video group showed a significant improvement in their handwashing performance, with a higher percentage of participants correctly performing all 7 steps compared with the control group (22.4% [95% CI, 13.1% to 31.6%] vs 1.5% [-7.9% to 10.9%]; P < .001). Hand scan images revealed that wrists, fingertips, and finger webs were the most commonly ignored areas in handwashing. Conclusions and Relevance: In this cluster randomized clinical trial of an education program for hand hygiene, a handwashing instructional video and hand scan images did not enhance the level of decontamination. The intervention group had improved handwashing techniques compared with the control group, a secondary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT05872581.

Strategies to increase the coverage of influenza and pneumonia vaccination in older adults: a systematic review and network meta-analysis.

BACKGROUND: It is urgent to implement interventions to increase vaccination rates of influenza/pneumonia vaccines in older adults, yet the effectiveness of different intervention strategies has not been thoroughly evaluated. OBJECTIVE: We aimed to assess the effectiveness of intervention strategies for increasing the coverage of influenza/pneumonia vaccination in older adults. METHODS: PubMed, Web of Science, Cochrane Library, Embase, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang were searched from 1 January 2000 to 1 October 2022. RCTs that assessed any intervention strategies for increasing influenza/pneumonia vaccination coverage or willingness in older adults were included. A series of random-effects network meta-analysis was conducted by using frequentist frameworks. RESULTS: Twenty-two RCTs involving 385,182 older participants were eligible for further analysis. Eight types of intervention strategies were evaluated. Compared with routine notification, health education (odds ratio [OR], 1.85 [95%CI, 1.19 to 2.88]), centralised reminder (OR, 1.63 [95%CI, 1.07 to 2.47]), health education + onsite vaccination (OR, 2.89 [95%CI, 1.30 to 6.39]), and health education + centralised reminder + onsite vaccination (OR, 20.76 [95%CI, 7.33 to 58.74]) could effectively improve the vaccination rate. The evidence grade was low or very low due to the substantial heterogeneity among studies. CONCLUSIONS: Our findings suggest that health education + centralised reminder + onsite vaccination may potentially be an effective strategy regardless of cost, but the evidence level was low. More rigorous trials are needed to identify the association between strategies and vaccination rates among older adults and to integrate such evidence into clinical care to improve vaccination rates.

Clinical prediction models for the early diagnosis of obstructive sleep apnea in stroke patients: a systematic review.

BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive cessation or reduction in airflow during sleep. Stroke patients have a higher risk of OSA, which can worsen their cognitive and functional disabilities, prolong their hospitalization, and increase their mortality rates. METHODS: We conducted a comprehensive literature search in the databases of PubMed, CINAHL, Embase, PsycINFO, Cochrane Library, and CNKI, using a combination of keywords and MeSH words in both English and Chinese. Studies published up to March 1, 2022, which reported the development and/or validation of clinical prediction models for OSA diagnosis in stroke patients. RESULTS: We identified 11 studies that met our inclusion criteria. Most of the studies used logistic regression models and machine learning approaches to predict the incidence of OSA in stroke patients. The most frequently selected predictors included body mass index, sex, neck circumference, snoring, and blood pressure. However, the predictive performance of these models ranged from poor to moderate, with the area under the receiver operating characteristic curve varying from 0.55 to 0.82. All the studies have a high overall risk of bias, mainly due to the small sample size and lack of external validation. CONCLUSION: Although clinical prediction models have shown the potential for diagnosing OSA in stroke patients, their limited accuracy and high risk of bias restrict their implications. Future studies should focus on developing advanced algorithms that incorporate more predictors from larger and representative samples and externally validating their performance to enhance their clinical applicability and accuracy.

Achieving improved full-spectrum responsive 0D/3D CuWO4/BiOBr:Yb3+,Er3+ photocatalyst with synergetic effects of up-conversion, photothermal effect and direct Z-scheme heterojunction.

The key to obtain effective photocatalysts is to increase the efficiency of light energy conversion, and thus the design and implementation of full-spectrum photocatalysts is a potential approach to solve this problem especially by extending the absorption range to near-infrared (NIR) light. Herein, the improved full-spectrum responsive CuWO4/BiOBr:Yb3+,Er3+ (CW/BYE) direct Z-scheme heterojunction was prepared. The CW/BYE with CW mass ratio of 5% had the best degradation performance, and the removal rate of tetracycline reached 93.9% in 60 min and 69.4% in 12 h under visible (Vis) and NIR light, respectively, which were 5.2 and 3.3 times of BYE. According to the outcome of experimental, the reasonable mechanism of improved photoactivity was put forward on the basis of (i) the up-conversion (UC) effect of Er3+ ion to convert NIR photon to ultraviolet or visible light, which can be used by CW and BYE, (ii) the photothermal effect of CW to absorb the NIR light, increasing the local temperature of photocatalyst particle to accelerate the photoreaction, and (iii) the formed direct Z-scheme heterojunction between BYE and CW to boost the separation of photogenerated electron-hole pairs. Additionally, the excellent photostability of the photocatalyst was verified by cycle degradation experiments. This work opens up a promising technique for designing and synthesizing full-spectrum photocatalysts by utilizing synergetic effects of UC, photothermal effect and direct Z-scheme heterojunction.

Challenges and Opportunities for Extracellular Vesicles in Clinical Oncology Therapy.

Extracellular vesicles (EVs) are membrane-bound vesicles that can be released by all cell types. They may have different biogenesis, physical features, and cargo. EVs are important biomarkers for the diagnosis and prediction of many diseases due to their essential role in intercellular communication, their highly variable cargoes, and their accumulation in various body fluids. These natural particles have been investigated as potential therapeutic materials for many diseases. In our previous studies, the clinical usage of tumor-cell-derived microparticles (T-MPs) as a novel medication delivery system was examined. This review summarizes the clinical translation of EVs and related clinical trials, aiming to provide suggestions for safer and more effective oncology therapeutic systems, particularly in biotherapeutic and immunotherapeutic systems.

A new approach to tumor immunobiological therapy：tumor vesicles / 中国肿瘤生物治疗杂志

@#[摘 要] 正常细胞及肿瘤细胞在发生凋亡或受到某些信号刺激时均可释放出直径为0.1~1 μm的膜状囊泡。肿瘤细胞受到信号刺激后骨架改变，导致细胞质膜包裹细胞内容物并向膜外侧起泡形成囊状小体，称为肿瘤囊泡，其不仅影响肿瘤细胞的生物学特性，对肿瘤免疫微环境也产生深刻的影响。除生物学效应外肿瘤囊泡还可作为一种天然的药物载体将治疗药物递送到肿瘤细胞，发挥抗肿瘤作用。研究证实，载药的肿瘤囊泡在天然免疫和获得性免疫反应中均体现良好的抗肿瘤激活效应，目前载药肿瘤囊泡已经进入临床应用阶段，在胆管癌、恶性胸腔积液的治疗中展现了良好的应用前景。

Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles.

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use ß-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.

FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an m6A-dependent manner.

FMR1, a new m6A reader, is known to be involved in the regulation of cancer progression. However, its role, regulatory mechanism, and clinical significance in colorectal cancer (CRC) are elusive. Here, we showed that FMR1 was upregulated in CRC, and it promoted proliferation and metastasis of CRC cells in vitro and in vivo. Mechanically, FMR1 recognized the m6A-modification site in EGFR mRNA, a key molecule in cancer occurrence and targeted therapy, sustained its stability and maintained its expression in an m6A-dependent manner, thereby promoting the tumorigenesis and metastasis of CRC. And the effect of FMR1 knockdown in CRC cells could be abolished by METTL3. Furthermore, FMR1 shRNA plasmid carried by attenuated Salmonella has an effective anti-tumor effect in vivo. Collectively, we identified the METTL3/FMR1/EGFR axis in the progression of CRC. This novel mechanism indicated that the METTL3/FMR1/EGFR axis is a potential target for early therapeutic intervention in CRC progression.

Retracted systematic reviews continued to be frequently cited: a citation analysis.

BACKGROUND AND OBJECTIVES: To survey the citations of retracted non-Cochrane systematic reviews (SRs) in scientific literature. METHODS: We searched the Web of Science and Google Scholar from their inception to 30 April 2020 to find the citations of 153 previously identified retracted non-Cochrane SRs. We calculated the numbers of citations before and after retraction separately. We also described how the citation addressed the retraction and how it was used in the article. RESULTS: A We identified 954 citations of 128 retracted SRs. The number of retracted SRs and citations reached the peak in 2014 and 2016, respectively, and the majority of the citations (n = 580, 60.8%) were in articles published after the SR was retracted. The mean number of citation per retracted SRs was 7.5. 2.6 before and 4.5 after the publication of the retraction notice. Twenty-nine (5.0%) citations indicated the retraction of the SRs in the reference section. Nine of these citations supported the retracted SR's results, and 15 disagreed with them. CONCLUSION: Retracted SRs continue to be cited after the publication of the retraction notice. Standardized methods are needed to guide the management of retractions and avoid inappropriate citations of retracted articles.

Role of endoplasmic reticulum stress in apoptosis induced by HK2 inhibitor and its potential as a new drug combination strategy.

Compared with normal cells, tumor cells mainly obtain energy through aerobic glycolysis. Hexokinase 2 (HK2) plays a key role in the regulation of tumor cell aerobic glycolysis, and targeting HK2 has become a new strategy for cancer treatment. However, little is known about the role of HK2 in colon cancer and the regulation of its targeted inhibitors. In this study, we found that the expression of HK2 in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the expression level of HK2 in metastatic colorectal cancer was further increased. Meanwhile, the expression level of HK2 was closely related to clinical TNM stage and outcome of colorectal cancer patients. We provide here evidence that HK2 inhibitor 3-Bromopyruvate acid (3-BP) can significantly inhibit the survival and proliferation of colon cancer cells, and induce apoptosis through mitochondrial apoptosis signaling pathway. In addition, we found that 3-BP can also induce endoplasmic reticulum stress in colon cancer cells, the mechanism may be through the increase of intracellular calcium concentration. In vitro and in vivo experiments showed that inhibition of endoplasmic reticulum stress could further increase the proliferation inhibition and apoptosis induced by 3-BP. Collectively, our results show that HK2 is highly expressed in colorectal cancer. 3-BP, an inhibitor of HK2, can induce apoptosis and endoplasmic reticulum stress in colon cancer cells. Endoplasmic reticulum stress plays a protective role in cell death induced by 3-BP. This result suggested that targeting HK2 and endoplasmic reticulum stress may be a valuable strategy in targeted and combination therapy of colon cancer.

Did patients with COVID-19 receive timely treatment in the early epidemic?-a systematic review and meta-analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) showed a significant difference in case fatality rate between different regions at the early stage of the epidemic. In addition to the well-known factors such as age structure, detection efficiency, and race, there was also a possibility that medical resource shortage caused the increase of the case fatality rate in some regions. METHODS: Medline, Cochrane Library, Embase, Web of Science, CBM, CNKI, and Wanfang of identified articles were searched through 29 June 2020. Cohort studies and case series with duration information on COVID-19 patients were included. Two independent reviewers extracted the data using a standardized data collection form and assessed the risk of bias. Data were synthesized through description and analysis methods including a meta-analysis. RESULTS: A total of 109 articles were retrieved. The time interval from onset to the first medical visit of COVID-19 patients in China was 3.38±1.55 days (corresponding intervals in Hubei province, non-Hubei provinces, Wuhan, Hubei provinces without Wuhan were 4.22±1.13, 3.10±1.57, 4.20±0.97, and 4.34±1.72 days, respectively). The time interval from onset to the hospitalization of COVID-19 patients in China was 8.35±6.83 days (same corresponding intervals were 12.94±7.43, 4.17±1.45, 14.86±7.12, and 5.36±1.19 days, respectively), and when it was outside China, this interval was 5.27±1.19 days. DISCUSSION: In the early stage of the COVID-19 epidemic, patients with COVID-19 did not receive timely treatment, resulting in a higher case fatality rate in Hubei province, partly due to the relatively insufficient and unequal medical resources. This research suggested that additional deaths caused by the out-of-control epidemic can be avoided if prevention and control work is carried out at the early stage of the epidemic. TRIAL REGISTRATION: CRD42020195606.

Reporting quality evaluation of the stroke clinical practice guidelines: a systematic review.

OBJECTIVES: To analyze the effectiveness and quality of stroke clinical practice guidelines (CPGs) published in recent years in order to guide future guideline developers to develop better guidelines. PARTICIPANTS: No patient involved METHOD: PubMed, China Biology Medicine (CBM), Wanfang, CNKI, and CPG-relevant websites were searched from January 2015 to December 2019 by two researchers independently. The RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was used to assess the reporting quality in terms of domains and items. Then, a subgroup analysis of the results was performed. PRIMARY AND SECONDARY OUTCOME MEASURES: RIGHT checklist reporting rate RESULTS: A total of 66 CPGs were included. Twice as many CPGs were published internationally as were published in China. More than half were updated. Most CPGs are published in journals, developed by societies or associations, and were evidence-based grading. The average reporting rate for all included CPGs was 47.6%. Basic information got the highest (71.7% ± 19.7%) reporting rate, while review and quality assurance got the lowest (22.0% ± 24.6%). Then, a cluster analysis between countries, publishing channels, and institutions was performed. There were no statistically significant differences in the reporting quality on the CPGs between publishing countries (China vs. international), publishing channels (journals vs. websites), and institutions (associations vs. non-associations). CONCLUSIONS: Current stroke CPGs reports are of low quality. We recommend that guideline developers improve the quality of reporting of key information and improve the management of conflicts of interest. We recommend that guideline developers consider the RIGHT checklist as an important tool for guideline development. TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/PBWUX .

Mortality and Clinical Interventions in Critically ill Patient With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Objective: The aims of this systematic review and meta-analysis were to summarize the current existing evidence on the outcome of critically ill patients with COVID-19 as well as to evaluate the effectiveness of clinical interventions. Data Sources: We searched MEDLINE, the Cochrane library, Web of Science, the China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data from their inception to May 15, 2021. The search strings consisted of various search terms related to the concepts of mortality of critically ill patients and clinical interventions. Study Selection: After eliminating duplicates, two reviewers independently screened all titles and abstracts first, and then the full texts of potentially relevant articles were reviewed to identify cohort studies and case series that focus on the mortality of critically ill patients and clinical interventions. Main Outcomes and Measures: The primary outcome was the mortality of critically ill patients with COVID-19. The secondary outcomes included all sorts of supportive care. Results: There were 27 cohort studies and six case series involving 42,219 participants that met our inclusion criteria. All-cause mortality in the intensive care unit (ICU) was 35% and mortality in hospital was 32% in critically ill patients with COVID-19 for the year 2020, with very high between-study heterogeneity (I 2 = 97%; p < 0.01). In a subgroup analysis, the mortality during ICU hospitalization in China was 39%, in Asia-except for China-it was 48%, in Europe it was 34%, in America it was 15%, and in the Middle East it was 39%. Non-surviving patients who had an older age [-8.10, 95% CI (-9.31 to -6.90)], a higher APACHE II score [-4.90, 95% CI (-6.54 to -3.27)], a higher SOFA score [-2.27, 95% CI (-2.95 to -1.59)], and a lower PaO2/FiO2 ratio [34.77, 95% CI (14.68 to 54.85)] than those who survived. Among clinical interventions, invasive mechanical ventilation [risk ratio (RR) 0.49, 95% CI (0.39-0.61)], kidney replacement therapy [RR 0.34, 95% CI (0.26-0.43)], and vasopressor [RR 0.54, 95% CI (0.34-0.88)] were used more in surviving patients. Conclusions: Mortality was high in critically ill patients with COVID-19 based on low-quality evidence and regional difference that existed. The early identification of critical characteristics and the use of support care help to indicate the outcome of critically ill patients.

PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer.

The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.

Analysis of COVID-19 Guideline Quality and Change of Recommendations: A Systematic Review.

Background: Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published. Methods: We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs. Results: We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence. Conclusions: Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform.

Clinical characteristics of children with COVID-19: a rapid review and meta-analysis.

BACKGROUND: Most guidelines on COVID-19 published so far include recommendations for patients regardless of age. Clinicians need a more accurate understanding of the clinical characteristics of children with COVID-19. METHODS: We searched studies reporting clinical characteristics in children with COVID-19 published until March 31, 2020. We screened the literature, extracted the data and evaluated the risk of bias and quality of evidence of the included studies. We combined some of the outcomes (symptoms) in a single-arm meta-analysis using a random-effects model. RESULTS: Our search retrieved 49 studies, including 25 case reports, 23 case series and one cohort study, with a total of 1,667 patients. Our meta-analysis showed that most children with COVID-19 have mild symptoms. Eighty-three percent of the children were within family clusters of cases, and 19% had no symptoms. At least 7% with digestive symptoms. The main symptoms of children were fever [48%, 95% confidence interval (CI): 39%, 56%] and cough (39%, 95% CI: 30%, 48%). The lymphocyte count was below normal level in only 15% (95% CI: 8%, 22%) of children which is different from adult patients. 66% (95% CI: 55%, 77%) of children had abnormal findings in CT imaging. CONCLUSIONS: Most children with COVID-19 have only mild symptoms, and many children are asymptomatic. Fever and cough are the most common symptoms in children. Vomiting and diarrhea were not common in children. The lymphocyte count is usually within the normal range in children.

Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis.

BACKGROUND: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. METHODS: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. RESULTS: A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. CONCLUSIONS: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.

Application of telemedicine during the coronavirus disease epidemics: a rapid review and meta-analysis.

BACKGROUND: As COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions. METHODS: We searched MEDLINE, Web of Science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies. RESULTS: A total of 2,041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases. CONCLUSIONS: Telemedicine services should focus on the issues that the public is most concerned about, such as the symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.