Analysis of pathogenic factors of retinopathy of prematurity in Heilongjiang Province (preprint)

Background and purpose Retinopathy of prematurity is a vascular development disorder in immature retinas of premature infants, which is the leading cause of blindness in children worldwide. Because the screening delay may lead to the occurrence of blindness in children, it is particularly important to conduct timely screening for children with high risk factors. Currently, the pathogenesis of ROP may be related to multiple factors such as gestational age and birth weight of premature infants. In this study, the prevalence and risk factors of ROP in Heilongjiang Province were determined through screening for premature infants in the region, aiming to proceed early prevention of the disease. Methods Retrospectively analyzed 714 premature infants admitted to the Ophthalmology Clinic of the Second Affiliated Hospital of Harbin Medical University from January 2016 to February 2022. 12 related factors was recorded including patients’ gender, gestational age, birth weight, oxygen duration, blood transfusions, anemia, neonatal infections, respiratory distress syndrome, maternal feeding way, childbirth way, pregnancy age and parity. The prevalence of ROP and the differences in related factors between ROP patientsand non-ROP patients were found. Results Among 714 premature infants, 188 had ROP of which the incidence is 26.3%，and 61 patients received treatment. There were statistically significance(P<0.05) in gestational age, birth weight, oxygen duration, blood transfusion, anemia, neonatal infection, respiratory distress syndrome and childbirth way between the 188 ROP patients and non-ROP patients in univariate regression analysis. Variables with statistical significance for single factor were selected and conducted by multivariate regression analysis, which showed that gestational age, birth weight, and oxygen duration had remarkable statistical significance(P<0.05) with the occurrence of ROP. Gestational age and birth weight were the protective factors of disease (OR=0.43 and OR=0.8), while oxygen duration was the risk factor of disease (OR=1.02), and the diagnostic value of the model was high (AUC=0.776). five of the 61 patients who received treatment for ROP accepted two treatments, with gestational age < 32 weeks, birth weight < 1500g, and oxygen inhalation time > 20 days. The Kendall grade relative analysis of 188 patients with ROP showed that disease severity was significantly correlated with gestational age, birth weight, oxygen duration, anemia, blood transfusion and respiratory distress syndrome(P<0.05), in which the gestational age, birth weight, anemia, blood transfusion and respiratory distress syndrome were negatively correlated with the severity of the disease, while oxygen duration was positively correlated with severity of the disease. 507 children were screened from 2016 to December 31th in 2019, 138 of which were ROP patients, 36 children were treated (7.1%). Due to the spread of the COVID-19, 207 children were screened after January 1th in 2020, 50 children were ROP patients, and 25 of whom got treatment (12%), 21were treated after 8 weeks of birth or more than 37 weeks of corrected gestational age. Four out of five children who received the second treatment happened after the epidemic, and three of them missed treatment due to the epidemic. Conclusions The gestational age, birth weight and oxygen duration are significantly correlated with the incidence and severity of the disease in premature infants screening of Heilongjiang Province. Premature infants screening and subsequent visit were affected due to the spread of the COVID-19 in the past two years, the proportion of children needed to be cured augmented apparently, therefore, it matters a lot for premature infants to be screened standardly and timely.

Comparison of different isolation periods for preventing the spread of COVID-19: a rapid systematic review and a modelling study (preprint)

Background: The optimal isolation duration for COVID-19 patients remains unclear. To support an update of WHO Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing onward transmission leading to hospitalization and death among secondary cases. Methods: We searched World Health Organization (WHO) COVID-19 database for clinical studies evaluating the impact of isolation periods for COVID-19 patients up to July 28, 2022. We performed random-effects meta-analyses to summarize testing rates of persistent test positivity rates after COVID-19 infection. We developed a model to compare the effects of the five-day isolation and removal of isolation based on a negative antigen test with ten-day isolation on onward transmission leading to hospitalization and death. We assumed that patients with a positive test are infectious and those with a negative test are not. If the test becomes negative, patients will stay negative. The model included estimates of test positivity rates, effective reproduction number, and hospitalization rate or case fatality rate. Findings: Twelve studies addressing persistent test positivity rates including 2799 patients proved eligible. Asymptomatic patients (27.1%, 95% CI: 15.8% to 40.0%) had a significantly lower rapid antigen test (RAT) positive rate than symptomatic patients (68.1%, 95% CI: 40.6% to 90.3%) on day 5. The RAT positive rate was 21.5% (95% CI: 0 to 64.1%; moderate certainty) on day 10. Our modelling study suggested that the risk difference (RD) for asymptomatic patients between five-day isolation and ten-day isolation in hospitalization (2 more hospitalizations of secondary cases per 1000 patients isolated, 95% uncertainty interval (UI) 2 more to 3 more) and mortality (1 more per 1000 patients, 95% UI 0 to 1 more) of secondary cases proved very small (very low certainty). For symptomatic patients, the potential impact of five- versus ten-day isolation was much greater in hospitalizations (RD 19 more per 1000 patients, 95% UI 14 more to 24 more; very low certainty) and mortality (RD 5 more per 1000 patients, 95% UI 4 more to 6 more; very low certainty). There may be no difference between removing isolation based on a negative antigen test and ten-day isolation in the onward transmission leading to hospitalization or death, but the average isolation period (mean difference -3 days) will be shorter for the removal of isolation based on a negative antigen test (moderate certainty). Interpretation: Five versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalization and mortality, but in symptomatic patients concerning transmission and resulting hospitalization and mortality. The evidence is, however, very uncertain.

From Molecular Dynamics to Supramolecular Organization: The Role of PIM Lipids in the Originality of the Mycobacterial Plasma Membrane (preprint)

Mycobacterium tuberculosis ( Mtb ) is the causative agent of tuberculosis, a disease that claims ~1.5 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. There is much to be understood about the Mtb cell envelope, a complicated barrier that antibiotics need to negotiate to enter the cell. Within this envelope, the plasma membrane is the ultimate obstacle and is proposed to be comprised of over 50% mannosylated phosphatidylinositol lipids (phosphatidyl- myo inositol mannosides, PIMs), whose role in the membrane structure remains elusive. Here we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to drive biophysical properties of the Mycobacterial plasma membrane. To validate the model, we tested known anti-tubercular drugs and replicated previous experimental results. Our results shed new light into the organization of the Mycobacterial plasma membrane and provides a working model of this complex membrane to use for in silico studies. This opens the door for new methods to probe potential antibiotic targets and further understand membrane protein function. Abstract Figure

Modelling the impact of rapid tests, tracing and distancing in lower-income countries suggest optimal policies varies with rural-urban settings (preprint)

Background Non-pharmaceutical intervention (NPI) remains the most reliable COVID-19 containment tool for low- and middle-income countries (LMICs) given the inequality of vaccine distribution and their vulnerable healthcare systems. We aimed to develop mathematical models that capture LMIC demographic characteristics such as young population and large household size and assess NPI effectiveness in rural and urban communities. Methods We constructed synthetic populations for rural, non-slum urban and slum settings to capture LMIC demographic characteristics that vary across communities. We integrated age mixing and household structure into contact networks for each community setting and simulated COVID-19 outbreaks within the networks. Using this agent-based model, we evaluate NPIs including testing and isolation, tracing and quarantine, and physical distancing. We explored the optimal containment strategies for rural and urban communities by designing and simulating setting-specific strategies that deploy rapid diagnostic test, symptom screening, contact tracing and physical distancing. We performed extensive simulations to capture the uncertainty of outbreak trajectories and the impact of varying model parameters. Findings We found the impact of testing, tracing and distancing varies with rural-urban settings. In rural communities, we found implementing either high quality (sensitivity > 50%) antigen rapid diagnostic tests or moderate physical distancing could contain the transmission. Additionally, antibody rapid diagnostic tests and symptom-based diagnosis could be useful for mitigating the transmission. In non-slum urban communities, we demonstrated that both physical distancing and case finding are essential for containing COVID-19 (average infection rate < 10%). In slum communities, we found physical distancing is less effective compared to rural and non-slum urban communities. Lastly, for all communities considered, we demonstrated contact quarantine is essential for effective containment and is effective at a low compliance rate (30%). Interpretation Our findings could guide setting-specific strategy design for different communities in LMICs. Our assessments also have implications on applying rapid diagnostic tests and symptom-based diagnosis for case finding, tracing and distancing in lower-income communities.

Prevalence of delirium, depression, anxiety, and post-traumatic stress disorder among COVID-19 patients: protocol for a living systematic review (preprint)

Background: Previous studies on the impact of corona virus disease 2019 (COVID-19) on the mental health of the patients has been limited by the lack of relevant data. With the rapid and sustained growth of the publications on COVID-19 research, we will perform a living systematic review (LSR) to provide comprehensive and continuously updated data to explore the prevalence of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) among COVID-19 patients. Methods: We will perform a comprehensive search of the following databases: Cochrane Library, PubMed, Web of Science, Embase, and Chinese Biomedicine Literature to identify relevant studies. We will include peer-reviewed cross-sectional studies published in English and Chinese. Two reviewers will independently assess the methodological quality of included studies using the Joanna Briggs Institute Prevalence Critical Appraisal tool and perform data extraction. In the absence of clinical heterogeneity, the prevalence estimates with a 95% confidence interval (CI) of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) will be calculated by using random-effects model to minimize the effect of between-study heterogeneity separately. The literature searches will be updated every three months. We will perform meta-analysis if any new eligible studies or data are obtained. We will resubmit an updated review when there were relevant changes in the results, i.e. when outcomes became statistically significant (or not statistically significant anymore) or when heterogeneity became substantial (or not substantial anymore). Discussion: This LSR will provide an in-depth and up-to-date summary of whether the common neuropsychiatric conditions observed in patients hospitalized for severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS) are also prevalent in a different stage of COVID-19 patients. Systematic review registration PROSPERO CRD42020196610

Characteristics of Registered Systematic Reviews on Treatment for COVID-19 in Prospero Platform (preprint)

Background: Characteristics and research collaboration of registered systematic reviews (SRs) on treatment for coronavirus disease 2019 (COVID-19) remain unclear. This study aimed to analyze research collaboration, interventions, and outcome measures in registered SRs of treatment associated with COVID-19 and point out the problem.Methods: PROSPERO was searched for SRs of treatment related to COVID-19 as of June 2, 2020. Excel 2016 was used for descriptive statistical analysis of the extracted information. VOSviewer 1.6.14 software was used to generate network maps for collaborations between countries and institutions.Results: A total of 189 SRs were included, which were registered by 301 institutions from 39 countries. China (69, 36.50%) was the country with the highest output. Cooperation between countries was not close enough. Chengdu university of traditional Chinese medicine (7, 3.70%) was the institutions with the highest output. There is close cooperation between institutions. Interventions included antiviral therapy (81, 42.86%), respiratory support (16, 8.47%), circulation support (11, 5.82%), plasma therapy for convalescent patients (11, 5.82%), immunotherapy (9, 4.76%), TCM Treatment (9, 4.76%), rehabilitation treatment (5, 2.65%), anti-inflammatory treatment (16, 8.47%), and other treatments (31, 16.40%). In antiviral therapy (81, 42.86%), the most commonly used drugs were chloroquine/hydroxychloroquine (26, 13.76%), followed by remdesivir (12, 6.35%), lobinavir/ritonavir(11, 5.82%), favipiravir (5, 2.65%), ribavirin (5, 2.65%), interferon (5, 2.65%), abiron (4, 2.12%), abidor (4, 2.12%), but the description was brief, and no specific implementation plan was provided. The most frequently used primary outcome was mortality rate (92, 48.68%), and the most frequently used secondary outcome was length of hospital stay (48, 25.40%). The expression of the outcomes was not standardized.Conclusions: Many COVID-19 SRs of treatment have been registered, but the completion rate was low. Although there were some collaborations between countries and institutions of the current registered SRs of treatment related to COVID-19 on PROSPERO, cooperation between countries should be further strengthened. More attention should be paid to the deficiency of interventions and outcome measures, and the standardization of results should be strengthened.

Characteristics of registered systematic reviews on traditional Chinese medicine for COVID-19 (preprint)

Background: Characteristics of registered systematic reviews (SRs) on traditional Chinese medicine (TCM) for coronavirus disease 2019 (COVID-19) remain unclear. This study aimed to analyze research collaboration, interventions, and outcomes in registered SRs of TCM associated with COVID-19.Methods: PROSPERO was searched to obtain SRs of TCM related to COVID-19 up to July 1, 2020. VOSviewer 1.6.14 software was used to generate network maps for countries, institutions, and provinces.Results: A total of 80 SRs were included, which were registered by 81 institutions from 6 countries. China (76, 95.00%) was the country with the highest output. 21 provinces in China contributed to the registration of SRs, Sichuan (25, 30.12%), Beijing (13, 15.66%), and Shaanxi (7, 8.43%) were the top three productive provinces. The top three productive institutions were Chengdu University of traditional Chinese medicine (18, 24.66%), Shaanxi University of traditional Chinese medicine (7, 9.59%), and Beijing University of traditional Chinese medicine (6, 8.22%). Collaborations among countries, provinces, and institutions were sparse. Interventions investigated included traditional Chinese medicine, integrated Chinese and Western medicine, acupuncture, and Taijiquan, but the description was brief, and no specific implementation plan was provided. The most frequently used primary outcome was clinical efficiency (45, 56.25%), and the most frequently used secondary outcome was the adverse event (50, 62.5%). The expression of the outcomes was not standardized.Conclusions: Although there were some collaborations between provinces and institutions, cooperation between countries should be further strengthened. The identified deficiencies in interventions and outcomes should be given more attention by future researchers.

Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis (preprint)

Background: Cancer patients are considered a highly vulnerable population in the COVID-19 epidemic, but the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aimed to explore the prevalence of cancer in patients with COVID-19 and to examine whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: A comprehensive electronic search in seven databases was performed, to identified studies reporting the prevalence of cancer in COVID-19 patients, or providing data of cancer between patients with severe or non-severe illness or between non-survivors and survivors. Meta-analyses were performed to estimate the pooled prevalence and odds risk (OR) using the inverse variance method with the random-effects model. Results: Thirty-four studies with 8080 patients were included. The pooled prevalence of cancer in patients with COVID-19 was 2.0% (95% CI: 2.0% to 3.0%). The prevalence in Italy (5.0%), France (6.0%), and Korea (4.0%) were higher than that in China (2.0%). Cancer was associated with a 2.84-fold significantly increased risk of severe illness (OR = 2.84, 95%CI: 1.75 to 4.62, P < 0.001) and a 2.60-fold increased risk of death (OR = 2.60, 95%CI: 1.28 to 5.26, P = 0.008) in patients with COVID-19. Sensitivity analyses showed that the results were stable after excluding studies with a sample size of less than 100. Conclusions: Cancer patients have an increased risk of COVID-19 and cancer was associated with a significantly increased risk of severity and mortality of patients with COVID-19.