Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study.

INTRODUCTION: The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study. METHODS: The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up. RESULTS: Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age. CONCLUSION: We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up. TRIAL REGISTRATION: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832. PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Self-Destructive Structural Color Liquids for Time-Temperature Indicating.

Vaccines are undoubtedly a powerful weapon in our fight against global pandemics, as demonstrated in the recent COVID-19 case, yet they often face significant challenges in reliable cold chain transport. Despite extensive efforts to monitor their time-temperature history, current time-temperature indicators (TTIs) suffer from limited reliability and stability, such as difficulty in avoiding human intervention, inapplicable to subzero temperatures, narrow tracking temperature ranges, or susceptibility to photobleaching. Herein, we develop a class of structural color materials that harnesses dual merits of fluidic nature and structural color, enabling thermal-triggered visible color destruction based on triggering agent-diffusion-induced irreversible disassembly of liquid colloidal photonic crystals for indicating the time-temperature history of the cold chain transport. These self-destructive structural color liquids (SCLs) exhibit inherent irreversibility, superior sensitivity, tunable self-destructive time (minutes to days), and a wide tracking temperature range (-70 to +37 °C). Such self-destructive SCLs can be conveniently packaged into flexible TTIs for monitoring the storage and exposure status of diverse vaccines via naked-eye inspection or mobile phone scanning. By overcoming the shortcomings inherent in conventional TTIs and responsive photonic crystals, these self-destructive SCLs can increase their compatibility with cold chain transport and hold promise for the development and application of the next-generation intelligent TTIs and photonic crystals.

External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients.

The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in critically ill coronavirus disease 19 (COVID-19) patients admitted to the ICU of the University Hospitals Leuven from February 2020 to January 2021. All patient-days that had serum creatinine levels available and measured creatinine clearance on the next ICU day were enrolled. The performance of the ARC predictor was evaluated using discrimination, calibration, and decision curves. A total of 120 patients (1064 patient-days) were included, and ARC was found in 57 (47.5%) patients, corresponding to 246 (23.1%) patient-days. The ARC predictor demonstrated good discrimination and calibration (AUROC of 0.86, calibration slope of 1.18, and calibration-in-the-large of 0.14) and a wide clinical-usefulness range. At the default classification threshold of 20% in the original study, the sensitivity and specificity were 72% and 81%, respectively. The ARC predictor is able to accurately predict ARC in critically ill COVID-19 patients. These results support the potential of the ARC predictor to optimize renally cleared drug dosages in this specific ICU population. Investigation of dosing regimen improvement was not included in this study and remains a challenge for future studies.

Using an implementation strategy to improve guideline-adherent delirium care in hospices: Emerging findings of the DAMPen-Delirium feasibility study

BackgroundDelirium is a complex condition, distressing for patients, family members and staff, and associated with poor outcomes. Despite high prevalence in the palliative care setting, it remains under-diagnosed. Delirium guideline-adherent care may both prevent and alleviate delirium. The best way to improve delirium-guideline adherence, and whether better adherence is reflected in reduced delirium, is not known. Prompt dissemination of feasibility findings is critical to avoid research waste.MethodsTo inform a definitive large study, working closely with Patient Public Involvement members, we conducted a co-design and feasibility study (ISRCTN55416525) to assess the feasibility of collecting data (delirium diagnosis;guideline-adherence) from clinical records. Clinical record data (evidence of: delirium using a validated chart-based instrument;guideline-adherent delirium care) was collected from 50 consecutive in-patient admissions at three hospices pre- and post-implementation of a co-designed implementation strategy (data collection completed 3 December 2022). Analysis: Pre-post comparison of percentages for continuous data (delirium outcomes);nominal data (raw count of guideline-adherent metrics).ResultsTarget clinical record data collection (n=300) was achieved within timeframe, despite data collection during COVID-19. Delirium prevalence was comparable pre-and post-implementation with two-thirds of patients having a delirium episode during admission. There was a reduction in the proportion of delirium-days during admission 62% to 49%. We observed modest post-implementation improvements in most guideline-adherent metrics: delirium diagnosis as documented by the clinical team 15% to 26%;evidence of reversibility 33% to 36%;delirium risk assessment 0% to 12.5%;screening on admission 21% to 35%.ConclusionData collection about delirium outcomes and guideline-adherence from hospice clinical records is feasible. Our findings show the disparity between need (high delirium-incidence) and documented action (low guideline-adherence). However, there is a signal of patient benefit even with small documented improvements which needs to be formally evaluated in a multi-site study of effectiveness of an implementation strategy for improving delirium guideline-adherence.

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis.

Background: Since the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics. Methods: Publications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis. Results: 1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: "Delta/Omicron variants", "cytokine storm", "neutralization/neutralizing antibody", "T cell", "BNT162b2", "mRNA vaccine", "vaccine effectiveness/safety", and "long COVID". Conclusion: This study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.

Investigating Students' Answering Behaviors in a Computer-Based Mathematics Algebra Test: A Cognitive-Load Perspective.

Computer-based testing is an emerging method to evaluate students' mathematics learning outcomes. However, algebra problems impose a high cognitive load due to requiring multiple calculation steps, which might reduce students' performance in computer-based testing. In order to understand students' cognitive load when answering algebra questions in a computer-based testing environment, three perspectives, element interactivity, practice effect, and individual differences, were investigated in this study. Seven levels of algebra exam questions were created using unary and simultaneous linear equations, and the inverse efficiency scores were employed as a measure of cognitive load in the study. Forty undergraduate and graduate students were tested. There were four findings: (1) As the element interactivity of test materials increased, the cognitive load increased rapidly. (2) The high-efficiency group had a lower cognitive load than the low-efficiency group, suggesting that the high-efficiency group had an advantage in a computer-based testing environment. (3) "Practice" has a considerable effect on reducing cognitive load, particularly in level 6 and 7 test items. (4) The low-efficiency group can reduce but not eliminate the gap with the high-efficiency group; they may require additional experience in a computer-based testing environment in order to improve reducing their cognitive load.

Response of Summer Maize Growth and Water Use to Different Irrigation Regimes

Summer maize crop development, yield, and water use characteristics under water deficit conditions at different growth stages were investigated in this study using different irrigation regime treatments at the seedling (S), jointing (J), tasseling (T), and grain filling stages (F) in 2018 and 2019 in China. Ten different irrigation treatments were set, including three-irrigation application intervals (JTFi, STFi, SJFi, SJTi), two-irrigation applications (STi, JTi, JFi), and single-irrigation applications (Ti, Ji). These were compared to the control treatment (CK), which had sufficient irrigation provided at four intervals (SJTFi). The results showed that compared to CK, a water deficit at the seedling and jointing stages had a greater effect on plant height, whereas a water deficit at the tasseling and filling stages had a greater effect on the leaf area index, and a continuous water deficit had an effect on the stem diameter of summer maize. Limitations in terms of the growth and development of summer maize increased with less frequent irrigation. As irrigation decreased, the grain yield decreased, and the water use efficiency increased, and a water deficit at the tasseling stage had the greatest effect on the yield and water use efficiency. The JTFi treatment was the optimal irrigation regime with a yield decline, and its water consumption was reduced by 16.9% (p < 0.05) on average. However, compared to CK, the water use efficiency of the JTFi treatment increased by 17.3% (p < 0.05). Moreover, the JTFi treatment had the smallest maize yield response factor value (Ky) of 0.16, and its comprehensive score was the second highest after CK. [ FROM AUTHOR] Copyright of Agronomy is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Epidemiological modelling in refugee and internally displaced people settlements: challenges and ways forward.

The spread of infectious diseases such as COVID-19 presents many challenges to healthcare systems and infrastructures across the world, exacerbating inequalities and leaving the world's most vulnerable populations at risk. Epidemiological modelling is vital to guiding evidence-informed or data-driven decision making. In forced displacement contexts, and in particular refugee and internally displaced people (IDP) settlements, it meets several challenges including data availability and quality, the applicability of existing models to those contexts, the accurate modelling of cultural differences or specificities of those operational settings, the communication of results and uncertainties, as well as the alignment of strategic goals between diverse partners in complex situations. In this paper, we systematically review the limited epidemiological modelling work applied to refugee and IDP settlements so far, and discuss challenges and identify lessons learnt from the process. With the likelihood of disease outbreaks expected to increase in the future as more people are displaced due to conflict and climate change, we call for the development of more approaches and models specifically designed to include the unique features and populations of refugee and IDP settlements. To strengthen collaboration between the modelling and the humanitarian public health communities, we propose a roadmap to encourage the development of systems and frameworks to share needs, build tools and coordinate responses in an efficient and scalable manner, both for this pandemic and for future outbreaks.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Correlation between vaccine coverage and the COVID-19 pandemic throughout the world: Based on real-world data.

The aim of the study was to examine the correlation between COVID-19 vaccine coverage rates and outcomes of the COVID-19 epidemic in the case of COVID-19 variants based on real-world data. The data came from Our World in Data, which is building the international COVID-19 vaccination data set and is an open-source data set for everyone to use. The vaccination data set uses the most recent official numbers from governments and health ministries worldwide. We assessed the correlation between COVID-19 vaccine coverage rates and outcomes of the COVID-19 epidemic with existing variants by performing temporal analysis and spatial analysis. Overall, new cases per million population, the reproduction rate of COVID-19, new deaths from all causes per million population, excess mortality attributed to COVID-19 pandemic, and hospital patients or intensive care unit (ICU) patients per million population were not decreased with the time course. However, at the same time point, new cases per million population, the reproduction rate of COVID-19, new deaths per million population, and hospital patients or ICU patients per million population gradually decreased as the rate of vaccination coverage increased. High coverage percentages of COVID-19 vaccination were negatively correlated with the reproduction rate of COVID-19 (correlation coefficient -0.116) and ICU patients per million of the local population (correlation coefficient -0.055). Currently, there is no effective treatment for the COVID-19 pandemic, and prevention of the COVID-19 pandemic mainly depends on vaccines, especially when the rate of COVID-19 vaccine coverage is over 60%. The benefits of preventing severe disease and preventing transmission of infection are likely to be obvious.

Study on the performance condition and impact mechanism of tourism system vulnerability under the impact of COVID-19: analysis of tourism data of the Chinese Spring Festival holiday in 2020

In order to study the impact degree of tourism system of the Spring Festival holiday in China under the impact of the COVID-19, this article establishes the concept and theory of performance vulnerability of a system by using the concept of vulnerability in the measurement of the effect degree of a system under the impact of disturbance factors. Combined with AHP and compositive evaluation method, we set up a vulnerability evaluation index system of tourism system to measure the index of performance vulnerability of the tourism system and its subsystems under the impact of the COVID-19, and discuss the impact mechanism model of the COVID-19 on the tourism system during the Spring Festival. The research shows that: the index of performance vulnerability of the tourism system in Spring Festival holiday is 0.6560, which reaches high vulnerability;the index of tourist market system is 0.7250, which reaches high vulnerability;the index of transportation system is 0.6930, which reaches high vulnerability;the index of central tourism enterprise system is 0.8714, which reaches severe vulnerability;the index of destination system is 0.8024, which reaches severe vulnerability;The index of support system is 0.1368, which reaches slight vulnerability.

Examining the association among fear of COVID-19, psychological distress, and delays in cancer care.

BACKGROUND: Given the high risk of COVID-19 mortality, patients with cancer may be vulnerable to fear of COVID-19, adverse psychological outcomes, and health care delays. METHODS: This longitudinal study surveyed the pandemic's impact on patients with cancer (N= 1529) receiving Patient Advocate Foundation services during early and later pandemic. Generalized estimating equation with repeated measures was conducted to assess the effect of COVID-19 on psychological distress. Logistic regression with repeated measures was used to assess the effect of COVID-19 on any delays in accessing health care (e.g., specialty care doctors, laboratory, or diagnostic testing, etc.). RESULTS: Among 1199 respondents, 94% considered themselves high risk for COVID-19. Respondents with more fear of COVID-19 had a higher mean psychological distress score (10.21; 95% confidence intervals [CI] 9.38-11.03) compared to respondents with less fear (7.55; 95% CI 6.75-8.36). Additionally, 47% reported delaying care. Respondents with more fear of COVID-19 had higher percentages of delayed care than those with less (56; 95% CI 39%-72% vs. 44%; 95% CI 28%-61%). These relationships persisted throughout the pandemic. For respondents with a COVID-19 diagnosis in their household (n = 116), distress scores were similar despite higher delays in care (58% vs. 27%) than those without COVID-19. CONCLUSIONS: Fear of COVID-19 is linked to psychological distress and delays in care among patients with cancer. Furthermore, those who are personally impacted see exacerbated cancer care delays. Timely psychosocial support and health care coordination are critical to meet increased care needs of patients with cancer during the COVID-19 pandemic.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Longitudinal trajectories of pneumonia lesions and lymphocyte counts associated with disease severity among convalescent COVID-19 patients: a group-based multi-trajectory analysis.

BACKGROUND: To explore the long-term trajectories considering pneumonia volumes and lymphocyte counts with individual data in COVID-19. METHODS: A cohort of 257 convalescent COVID-19 patients (131 male and 126 females) were included. Group-based multi-trajectory modelling was applied to identify different trajectories in terms of pneumonia lesion percentage and lymphocyte counts covering the time from onset to post-discharge follow-ups. We studied the basic characteristics and disease severity associated with the trajectories. RESULTS: We characterised four distinct trajectory subgroups. (1) Group 1 (13.9%), pneumonia increased until a peak lesion percentage of 1.9% (IQR 0.7-4.4) before absorption. The slightly decreased lymphocyte rapidly recovered to the top half of the normal range. (2) Group 2 (44.7%), the peak lesion percentage was 7.2% (IQR 3.2-12.7). The abnormal lymphocyte count restored to normal soon. (3) Group 3 (26.0%), the peak lesion percentage reached 14.2% (IQR 8.5-19.8). The lymphocytes continuously dropped to 0.75 × 109/L after one day post-onset before slowly recovering. (4) Group 4 (15.4%), the peak lesion percentage reached 41.4% (IQR 34.8-47.9), much higher than other groups. Lymphopenia was aggravated until the lymphocytes declined to 0.80 × 109/L on the fourth day and slowly recovered later. Patients in the higher order groups were older and more likely to have hypertension and diabetes (all P values < 0.05), and have more severe disease. CONCLUSIONS: Our findings provide new insights to understand the heterogeneous natural courses of COVID-19 patients and the associations of distinct trajectories with disease severity, which is essential to improve the early risk assessment, patient monitoring, and follow-up schedule.

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1.

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm for breath phase detection and adventitious sound detection at the recording level has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchus labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests using long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.

Extracorporeal Membrane Oxygenation Therapy for Critically Ill Coronavirus Disease 2019 Patients in Wuhan, China: A Retrospective Multicenter Cohort Study.

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Witnesses and Victims Both: Healthcare Workers and Grief in the Time of COVID-19.

Heathcare Workers (HCWs) recognize their responsibility to support the bereaved loved ones of our patients, but we also must attend to our own professional and personal grief in the COVID-19 pandemic. COVID-19 grief is occurring in the setting of incomplete grief, disenfranchised grief, fractured US governmental leadership, and evidence of great mistrust, systemic racism, and social injustice. In the intensity and pervasiveness of COVID-19, HCW fears for themselves, their colleagues, and their own loved ones are often in conflict with professional commitments. Even at the dawn of promising national and global vaccination programs, significant HCW morbidity and mortality in COVID-19 has already become clear, will continue to grow, and these effects likely will last far into the future. Given the risks of complicated grief for HCWs in the setting of COVID-19 deaths, individual HCWs must put every effort into their own preparation for these deaths as well as into their own healthy grieving. Equally importantly, our healthcare systems have a primary responsibility both to prepare HCWs and to support them in their anticipatory and realized grief. Special attention must be paid to our HCW trainees, who may have not yet developed personal or professional grief management strategies and are coming into healthcare practice during a time of great disruption to both teaching and clinical care.

Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.

Preliminary investigation of relationship between clinical indicators and CT manifestation patterns of COVID-19 pneumonia improvement.

BACKGROUND: To retrospectively evaluate several clinical indicators related to the improvement of COVID-19 pneumonia on CT. METHODS: A total of 62 patients with COVID-19 pneumonia were included. The CT scores based on lesion patterns and distributions in serial CT were investigated. The improvement and deterioration of pneumonia was assessed based on the changes of CT scores. Grouped by using the temperature, serum lymphocytes and high sensitivity CRP (hs-CRP) on admission respectively, the CT scores on admission, at peak time and at discharge were evaluated. Correlation analysis was carried out between the time to onset of pneumonia resolution on CT images and the recovery time of temperature, negative conversion of viral nucleic acid, serum lymphocytes and hs-CRP. RESULTS: The CT scores of the fever group and lymphopenia group were significantly higher than those of normal group on admission, at peak time and at discharge; and the CT scores of normal hs-CRP group were significantly lower than those of the elevated hs-CRP group at peak time and at discharge (P all<0.05). The time to onset of pneumonia resolution on CT image was moderately correlated with negative conversion duration of viral nucleic acid (r =0.501, P<0.05) and the recovery time of hs-CPR (r =0.496, P<0.05). CONCLUSIONS: COVID-19 pneumonia patients with no fever, normal lymphocytes and hs-CRP had mild lesions on admission, and presented with more absorption and fewer pulmonary lesions on discharge. The negative conversion duration of viral nucleic acid and the recovery time of hs-CPR may be the indicator of the pneumonia resolution.