Early prone positioning under VV-ECMO in SARS- CoV-2-induced acute respiratory distress syndrome - a retrospective cohort study

Objectives: The effectiveness of prone positioning (PP) under VV-ECMO for severe COVID-19 still be unclear. Until now, PP under VV-ECMO was often performed as the trump card for refractory hypoxemia and weaning off ECMO. On the other hand, PP has the effect of promoting homogenization of Lung aeration and leading to prevention of VILI. Combine use of early prone positioning together VV-ECMO may have synergy effects of ultra-lung protective strategy. In this study, we analyzed early PP cases under VV-ECMO for severe COVID-19 in our hospital and examined their efficacy and feasibility. Method(s): We performed a retrospective study of patients with SARS-CoV-2-induced ARDS submitted to early PP during VV-ECMO. During VVECMO, PP was considered in case of "Type-H transition in imaging findings (CT / LUS) " and cases that the physician deemed necessary. The lung aeration is evaluated by LUS before and after each PP. If there is a finding that the dorsal collapsed lung is improved through PP, it is implemented as effective, and it continued. Result(s): From April 2021 to August 2021, there were a total of 10 early PP cases under ECMO, and the age was (average) 56 years. ECMO was implanted with P/F 98 and Murray score 3.3 points, and PP was started 14 hours after the ECMO implantation. The average PP duration is 17.4 hours and PP performed 5.8 times per patient. Comparing blood gas and respiratory mechanics before and after PP showed a significant difference in PaCO2 (before: 46 +/- 8 vs after: 42 +/- 9, p = 0.02). Finally, there were 10 ECMO successful weaning (100%) and 8 surviving discharges (80%). No major complications were observed. Conclusion(s): Early PP under VV-ECMO for severe COVID-19 can be safely performed, and it is suggested that the synergy effect of ultra-lung protective strategy may be associated with a reduction of hospital mortality.

Search method for two cutoff values in clinical trial using Kruskal-Wallis test by minimum P-value approach

In clinical trials, age is often converted to binary data by the cutoff value. However, when looking at a scatter plot for a group of patients whose age is larger than or equal to the cutoff value, age and outcome may not be related. If the group whose age is greater than or equal to the cutoff value is further divided into two groups, the older of the two groups may appear to be at lower risk. In this case, it may be necessary to further divide the group of patients whose age is greater than or equal to the cutoff value into two groups. This study provides a method for determining which of the two or three groups is the best split. The following two methods are used to divide the data. The existing method, the Wilcoxon-Mann-Whitney test by minimum P-value approach, divides data into two groups by one cutoff value. A new method, the Kruskal-Wallis test by minimum P-value approach, divides data into three groups by two cutoff values. Of the two tests, the one with the smaller P-value is used. Because this was a new decision procedure, it was tested using Monte Carlo simulations (MCSs) before application to the available COVID-19 data. The MCS results showed that this method performs well. In the COVID-19 data, it was optimal to divide into three groups by two cutoff values of 60 and 70 years old. By looking at COVID-19 data separated into three groups according to the two cutoff values, it was confirmed that each group had different features. We provided the R code that can be used to replicate the results of this manuscript. Another practical example can be performed by replacing x and y with appropriate ones.

Incidence of acute exacerbation in patients with interstitial lung disease after COVID-19 vaccination

Acute exacerbations due to COVID-19 vaccination in patients with interstitial lung disease (ILD) have been reported, but their incidence is unknown. We investigated the incidence of exacerbations of ILD and respiratory symptoms due to the mRNA COVID-19 vaccines. A questionnaire survey was conducted on adverse reactions to the mRNA COVID-19 vaccination in 545 patients with ILD attending our hospital and retrospectively examined whether the eligible patients actually developed acute exacerbations of ILD induced by the vaccine. Of the 545 patients, 17 (3.1%) patients were aware of the exacerbation of respiratory symptoms, and four (0.7%) patients developed an acute ILD exacerbation after vaccination. Of the four patients who experienced exacerbations, two had collagen vascular disease-associated ILD, one had nonspecific interstitial pneumonia, another had unclassifiable idiopathic pneumonia, and none had idiopathic pulmonary fibrosis. Four patients were treated using steroid pulse therapy with a steroid taper, and two of the four also received intravenous cyclophosphamide pulse therapy. Tacrolimus was started in one patient with myositis-associated interstitial lung disease. Eventually, all patients exhibited improvement with immunosuppressive treatment and were discharged. COVID-19 vaccination for patients with ILD should be noted for developing acute exacerbations of ILD with low incidence, although manageable with early diagnosis and treatment. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Study Protocol for a Randomized Double-blind Placebo-controlled Phase 2 Clinical Trial to Assess Anti-inflammatory Effect of Colchicine(DRC3633)in Mild to Moderately Severe COVID-19 Patients(DRC-06C)

Introduction: Given that coronavirus disease 2019(COVID-19)aggravation is associated with an excessive host immune response, complementary anti-inflammatory treatment is recommended in severe disease. Although dexamethasone is a widely used anti-inflammatory agent in COVID-19 patients with respiratory failure, its use in patients with mild COVID-19 not receiving oxygen could have harmful effects. Colchicine, an anti-inflammatory drug, blocks the upstream immune response by inhibiting NALP3 inflammasome activation. This study aimed to assess the efficacy and safety of low-dose colchicine(DRC 3633)in mild COVID-19. Method(s): This study is a prospective, multicenter, placebo-controlled, double-blind randomized, phase 2 clinical trial patients with moderate COVID-19 admitted at nine hospitals in Japan (jRCT2071200078). The primary endpoint is area under the curve(AUC)for the amount of change of serum hypersensitive C-reactive protein(hs-CRP)from baseline to 1, 2, and 4 weeks after initiating investigational drug. Study participants will be randomly assigned to the colchicine or placebo group at a 1:1 ratio. On day 1, patients in the colchicine group will receive 1 mg of colchicine, followed by 0.5 mg of colchicine after 2 h barring gastrointestinal complications. From day 2 to 28, 0.5 mg of colchicine will be administered once daily. Discussion(s): An appropriate anti-inflammatory strategy is critical to improve the outcome of severe COVID-19 patients. This study will assess the efficacy of low-dose colchicine not only by the AUC of the amount of change in serum hs-CRP from baseline to several time points, but also by evaluating whether the result of the primary endpoint is consistent with other relevant biomarkers and clinical parameters measured as secondary endpoints. Copyright © 2022 the Japanese Society of Clinical Pharmacology and Therapeutics (JSCPT)

Impact of high/low-volume hospitals of ECMO before the COVID-19 pandemic era on ECMO outcomes in patients with fatal COVID-19

Introduction: The impact of treatment experience with ECMO prior to the COVID-19 pandemic era on the outcomes of ECMO during the COVID-19 pandemic has not been well investigated. The aim of this study was to investigate the differences in the outcomes of ECMO between highvolume hospitals in Japan before the COVID-19 pandemic and low-volume hospitals. Method(s): This is a prospective observational cohort study of patients with fatal COVID-19 pneumonia in Japan receiving ECMO. The association between patient background, high/low-volume hospitals, and survival from February 2020 to November 2021 were evaluated. Prognostic factors were assessed by Kaplan-Meier and Cox proportional hazards analyses. High-volume hospitals were defined as those with a total of at least 20 cases prior to the COVID-19 pandemic era. Result(s): Ten hospitals (1.1% of a total of 900 ICUs in Japan) were classified as high-volume hospitals, with a median number of ECMO cases of 35.5 (IQR, 25.5-40.5). There were a total of 1,214 ECMO cases during the COVID-19 pandemic, of which 1030 (85%) were treated in low-volume hospitals and 184 (15%) were treated in high-volume hospitals. Kaplan-Meier analysis demonstrated slightly better survival in high-volume hospitals in 30-day (p=0.062) and 60-day (p=0.11) survivals, whereas, in 90-day survival, the two groups were almost identical (p=0.87). Cox proportional hazards analysis also failed to demonstrate that high-volume hospital before the COVID-19 pandemic era was independent prognostic factor (HR, 0.97;95%CI, 0.74-1.28). Conclusion(s): In Japan, high-volume hospital prior to the COVID-19 pandemic era was not independent prognostic factor.

Incidence of acute exacerbation in patients with interstitial lung disease after COVID-19 vaccination

Acute exacerbations due to COVID-19 vaccination in patients with interstitial lung disease (ILD) have been reported, but their incidence is unknown. We investigated the incidence of exacerbations of ILD and respiratory symptoms due to the mRNA COVID-19 vaccines. A questionnaire survey was conducted on adverse reactions to the mRNA COVID-19 vaccination in 545 patients with ILD attending our hospital and retrospectively examined whether the eligible patients actually developed acute exacerbations of ILD induced by the vaccine. Of the 545 patients, 17 (3.1%) patients were aware of the exacerbation of respiratory symptoms, and four (0.7%) patients developed an acute ILD exacerbation after vaccination. Of the four patients who experienced exacerbations, two had collagen vascular disease-associated ILD, one had nonspecific interstitial pneumonia, another had unclassifiable idiopathic pneumonia, and none had idiopathic pulmonary fibrosis. Four patients were treated using steroid pulse therapy with a steroid taper, and two of the four also received intravenous cyclophosphamide pulse therapy. Tacrolimus was started in one patient with myositis-associated interstitial lung disease. Eventually, all patients exhibited improvement with immunosuppressive treatment and were discharged. COVID-19 vaccination for patients with ILD should be noted for developing acute exacerbations of ILD with low incidence, although manageable with early diagnosis and treatment.

Development of a contactless operation system for radiographic consoles using an eye tracker for severe acute respiratory syndrome coronavirus 2 infection control: a feasibility study

Sterilization of medical equipment in isolation wards is essential to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Particularly, the radiographic console of portable X-ray machines requires frequent disinfection because it is regularly moved;this requires considerable infection control effort as the number of patients with coronavirus disease 2019 (COVID-19) increases. To evaluate the application of a system facilitating noncontact operation of radiographic consoles for patients with COVID-19 to reduce the need for frequent disinfection. We developed a noncontact operation system for radiographic consoles that used a common eye tracker. We compared calibration errors between with and without face shield conditions. Moreover, the use of console operation among 41 participants was investigated. The calibration error of the eye tracker between with and without face shield conditions did not significantly differ. All (n = 41) observers completed the console operation. Pearson's correlation coefficient analysis showed a strong correlation (r = 0.92, P < 0.001) between the average operation time and the average number of misoperations. Our system that used an eye tracker can be applied even if the operator uses a face shield. Thus, its application is important in preventing the transmission of infection. © 2022 International Measurement Confederation (IMEKO). All rights reserved.

Estimation of highly heterogeneous multinomial probabilities observed at the beginning of COVID-19

The daily counts of COVID-19 cases differed significantly from one region to another at the beginning of the COVID-19 pandemic in any given country. The disease first hit some regions before spreading to others. The Poisson distribution is frequently used to analyze disease occurrence in certain locations at certain times. However, in highly heterogeneous situations, the estimator of multiple Poisson means is not close to the actual population parameter. The estimator of multinomial probabilities under an existing prior is also not close to the actual population parameter in highly heterogeneous situations. We propose a Bayesian estimator of multinomial probabilities under a data-dependent prior. This prior is built using zeta distribution coefficients and depends only on the rank of data. Using simulation studies, the proposed estimator is evaluated with two well-known risks. Finally, the daily counts of COVID-19 cases are analyzed to show how the proposed estimator can be used in practice.