Low-flow Oxygen Therapy Research Articles

Options for optimizing noninvasive respiratory support in the development of hypoxemic acute respiratory failure

Introduction. Acute respiratory failure (ARF) remains one of the most relevant problems of modern medicine and intensive care, and respiratory support (RS) remains the indispensable method of temporary external respiratory function replacement. Despite of widespread use of non-invasive ventilation (NIV) in clinical practice, at present systematic scientific data about possibilities for optimizing the use of these methods of RS in patients with hypoxemic ARF development is absent. It can be assumed that the combination of mask NIV and high-flow oxygen therapy (HFOT) at the stage of ARF development can improve results of treatment in this group of patients.The objective was to improve the results of treatment in patients with hypoxemic ARF through the combined use of mask NIV and HFOT.Materials and methods. The prospective cohort study included 77 patients aged 46.8 ± 11.8 years. Patients were randomized into three groups: in group A, RS was performed by using NIV and traditional low-flow oxygen therapy, in group B – by using HFOT, in group C – by sequential combination of NIV sessions and HFOT. The groups compared gas exchange rates, RS duration, intubation rate and nosocomial pneumonia (NP) incidence, length of treatment in the intensive care unit (ICU) and hospitalizations, overall mortality, and prognostic factors for tracheal intubation were also studied.Results. The combination of mask NIV and HFOT was found to be more clinically effective compared to their separate use. Combination of mask NIV and HFOT had the best effect on gas exchange rates in the long term period, reduced RS duration, intubation rate and pneumonia incidence, ICU treatment duration. Risk factors for tracheal intubation were revealed: RS duration more than 4.5 days, intra-abdominal pressure (IAP) more than 18 cm of water.Conclusions. The combination of mask NIV and HFOT increases the therapeutic potential of each of these RS methods and improves the results of treatment in patients with hypoxemic ARF development.

TREATMENT OF PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH CONGENITAL HEART DEFECTS

Patients with pulmonary arterial hypertension, associated with congenital heart disease (PAH-CHD) are a heterogeneous population with a varied course of PH. Improvements in pediatric cardiac surgery have changed the epidemiology and survival rate of patients with CHD, of which 90% reach adulthood. Progress in terms of prognosis has also been observed among patients with PAH-CHD. Better survival was observed in ES compared with PAH after defect correction. Advances in surgical treatment of CHD and an increase in life expectancy have led to the study of PAH-CHD and the need to create recommendations for drug treatment of this category of patients. In most of studies, the evaluation of drug treatment of group 1 PAH was carried out without identifying its subgroups. And thus, according to existing recommendations, treatment algorhithms for patients with PAH-CHD are similar to approaches to other forms of PAH. However, various clinical, functional, physical and hemodynamic characteristics of patients with PAH-CHD call into question of correct risk stratification approaches development. Multicenter randomized clinical trials included predominantly a small number of patients with corrected defects, which does not allow the results to be interpreted for the entire population of patients with PAH-CHD. Data from single-center observational studies, expert opinion, and several randomized trials primarily involving patients with Eisenmenger syndrome (ES) indicate the effectiveness and safety of PAH-specific therapy in patients with PAH-CHD. In this literature review, we examined and showed the results of studies involving patients with PAH-CHD and their response to specific therapy. The results obtained significantly expanded the possibilities of using bosentan, sildenafil, epoprostenol, riociguat, ralinepag, sotatercept as they lead to improvement of functional capacity and hemodynamic parameters in patients with PAH-CHD, and only epoprostenol demonstrated an effect on prognosis. Combination PAH-specific therapy, initial or sequential administration of two or more drugs with different mechanisms of action, is an important treatment strategy for patients with PAH. The role of such therapy has increased in recent years. Based on the results of the AMBITION, SERAPHIN, GRIPHON, COMPASS-2 studies, initial or sequential oral combination PAH-specific therapy is recommended for patients with WHO FC II or III. At the same time, there is little evidence to support the effectiveness of this approach in ES patients. The use of anticoagulants in PAH-CHD remains controversial. Low-flow oxygen therapy should be considered individually and continued when there is a significant predominance of subjective or objective benefit. Iron deficiency is associated with poor survival in ES. It is important to note that microcytosis is rare in patients with iron deficiency cyanosis and a normal mean red cell volume does not indicate the absence of anemia. In cases of intolerance to oral iron, intravenous drugs should be used. Currently, based on existing guidelines, most centers follow a consistent symptom-based approach in the treatment of patients with PAH-CHD. Therapy begins with oral ERAs or PDE-5 inhibitors and is escalated if symptoms persist or clinical worsening occurs. If there is no effect of oral PAH-specific therapy, it is recommended to consider parenteral drugs.

Reliability of digital filtering on surface electromyographic activity of respiratory muscles in patients with COVID-19

Introduction: Surface electromyography (sEMG) is valuable for assessing respiratory muscle activity, but the influence of electromagnetic fields can impair the accuracy of the signals. This study aims to compare the Root Mean Square (RMS) values of sEMG signals from respiratory muscles in COVID-19 patients receiving oxygen therapy in the ICU before and after digital filtering. Methods: This exploratory analysis is part of a cross-sectional study registered on ClinicalTrials.gov (NCT05572853). sEMG signals from the sternocleidomastoid, scalenus, diaphragm, and rectus abdominis muscles were recorded in COVID-19 patients receiving low-flow oxygen therapy. The RMS data were analyzed and processed using Scilab 6.1.1 software before and after applying a filter with a 60 Hz notch and a passband between 20-500 Hz. Results: 71 patients with a mean age of 55 ± 14 years, predominantly male (73.2%), were included. Muscle’s activity remained unchanged after signal filtering, showing higher RMS intensity (pre-filter/post-filter) for the scalene (14.0 ± 8.6 / 8.5 ± 6.2), sternocleidomastoid (12.0 ± 8.8 / 6.8 ± 7.8), diaphragm (11.7 ± 8.1 / 5.4 ± 7.1), and rectus abdominis (10.4 ± 4.7 / 3.1 ± 1.9) muscles. RMS attenuation was significant for all muscles (p < 0.001), with no agreement between pre- and post-filtering from Bland-Altman analysis. Conclusions: The applied digital filter attenuated RMS values while maintaining the same respiratory muscle activation, enhancing signal identification by reducing noise.

Pregnancy and COVID—Complications and its Challenges: A Case Series from a Tertiary Care Center in the Northeastern Part of India

The objective was to describe the course of management of all the coronavirus disease 2019 (COVID-19)-positive pregnant women, admitted to a 150-bedded tertiary care center in Guwahati, Assam, from March 01, 2021, till June 15, 2021. We collected a case series of 13 COVID-19-positive pregnant women, mostly in their second and third trimesters, admitted to our center between March 01, 2021, and June 15, 2021. All of the cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed by a positive result on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests. We aimed to show the course of management and maternal outcomes in these cases. The Results show that among the 13 infected pregnant women, three presented with severe SARS-CoV-2 pneumonia and were treated in the intensive care unit (ICU) and the rest were treated in wards as the mild category and discharged successfully. Two among them required invasive mechanical ventilation (IMV), and one was managed on non-invasive ventilation (NIV). Of the two mechanically ventilated patients, one succumbed to the illness and the other patient was successfully weaned in 5 days and shifted out after 15 days of the ICU stay. The third patient was on NIV support for 7 days, weaned off to low-flow oxygen therapy via face mask/ nasal prongs, and shifted out after 17 days of the ICU stay. Data on pregnant women with coronavirus infection are scarce and contradictory as the effect of SARS-CoV-2 on pregnancy is not clear. It is highly important to systemically investigate the clinical characteristics and outcomes of pregnant women with COVID-19 to provide strong guidelines for prevention, treatment, and management.

Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial – the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study

RationaleAcute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive...

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit

Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.

COVID-19 admissions: Trying to define the real impact of infection in hospitalized patients

Introduction and objectiveSeveral studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. MethodsRetrospective cohort study including patients aged 0–18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children’s hospital in Spain between 01/01/2020 and 12/31/2021. Results228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization).In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. ConclusionsIn our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1–59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial

The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. SIDA Sweden and Grand Challenges Ethiopia.

High-flow nasal cannula therapy for infants with bronchiolitis.

Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is the most common cause of hospitalisation of infants. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality. Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen, and respiratory support. Traditionally, oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, at 2 to 3 L/kg per minute up to 60 L/min in children. It can provide some level of continuous positive airway pressure (CPAP) to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support, thus potentially lowering costs, with clinical advantages and fewer adverse effects. To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, and Web of Science (from June 2013 to December 2022). In addition, we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles, and searched for conference abstracts. Date restrictions were imposed such that we only searched for studies published after the original version of this review. We included randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/minute) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis. Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, risk of bias elements, and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy, and adverse events. In this update we included 15 new RCTs (2794 participants), bringing the total number of RCTs to 16 (2813 participants). Of the 16 studies, 11 compared high-flow to low-flow, and five compared high-flow to CPAP. These studies included infants less than 24 months of age as stated in our selection criteria. There were no significant differences in sex. We found that when comparing high-flow to low-flow oxygen therapy for infants with bronchiolitis there may be a reduction in the total length of hospital stay (mean difference (MD) -0.65 days, 95% confidence interval (CI) -1.23 to -0.06; P < 0.00001, I2 = 89%; 7 studies, 1951 participants; low-certainty evidence). There may also be a reduction in the duration of oxygen therapy (MD -0.59 days, 95% CI -1 to -0.18; P < 0.00001, I2 = 86%; 7 studies, 2132 participants; low-certainty evidence). We also found that there was probably an improvement in respiratory rate at one and 24 hours, and heart rate at one, four to six, and 24 hours in those receiving high-flow oxygen therapy when compared to pre-intervention baselines. There was also probably a reduced risk of treatment escalation in those receiving high-flow when compared to low-flow oxygen therapy (risk ratio (RR) 0.55, 95% CI 0.39 to 0.79; P = 0.001, I2 = 43%; 8 studies, 2215 participants; moderate-certainty evidence). We found no difference in the incidence of adverse events (RR 1.2, 95% CI 0.38 to 3.74; P = 0.76, I2 = 26%; 4 studies, 1789 participants; low-certainty evidence) between the two groups. The lack of comparable outcomes in studies comparing high-flow and CPAP, as well as the small numbers of participants, limited our ability to perform meta-analysis on this group. High-flow nasal cannula therapy may have some benefits over low-flow oxygen for infants with bronchiolitis in terms of a greater improvement in respiratory and heart rates, as well as a modest reduction in the length of hospital stay and duration of oxygen therapy, with a reduced incidence of treatment escalation. There does not appear to be a difference in the number of adverse events. Further studies comparing high-flow nasal cannula therapy and CPAP are required to demonstrate the efficacy of one modality over the other. A standardised clinical definition of bronchiolitis, as well as the use of a validated clinical severity score, would allow for greater and more accurate comparison between studies.

Ingresos COVID-19: intentando comprender el impacto real de la infección en pacientes hospitalizados

Introduction and objectiveSeveral studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. MethodsRetrospective cohort study including patients aged 0 to 18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021. Results228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization).In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. ConclusionsIn our study, one third of the patients were admitted with SARS-CoV-2 infection but not becauseof it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support.

To discover potential micro(mi)RNA biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep-sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9-24] days since symptoms initiation) and 21 healthy noninfected individuals. A total of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2-infected patients showed significantly (fold change [FC] > 1.2 and adjusted p [padj] < 0.05) altered expression of 190 miRNAs. The top-10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin, and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found, when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow.

Implementation of bubble continuous positive airway pressure for children with severe pneumonia and hypoxemia in intensive care unit of Dhaka Hospital, Bangladesh-Effect on pneumonia mortality.

After the completion of a randomized trial at Dhaka Hospital in 2013, bubble continuous positive airway pressure (BCPAP) oxygen therapy was incorporated as the part of the standard treatment for children with severe pneumonia with hypoxemia in an intensive care unit at Dhaka Hospital in August 2013 instead of World Health Organization (WHO) standard low flow oxygen therapy. To understand the long-term effectiveness of the introduction of bCPAP oxygen therapy by comparing pneumonia mortality in the post-trial period (August 2013 to December 2017) with the pre-trial (February 2009 to July 2011) and trial periods (August 2011 to July 2013). It was a retrospective analysis of prospectively collected hospital data of all admissions. Mortality rates of all children with WHO-defined pneumonia, and the subset of children with severe pneumonia and hypoxemia (oxygen saturation <90%) were evaluated. The analysis covered 10,107 children with pneumonia: 2523 in the pre-trial (414 with severe pneumonia and hypoxemia; none of them received bCPAP), 2959 during the trial (376 with severe pneumonia and hypoxemia; 79 received bCPAP), and 4625 in the post-trial period (1208 with severe pneumonia and hypoxemia; 1125 had bCPAP). The risk of death from pneumonia in the post-trial period was lower than in pre-trial (adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58-0.92; p = 0.007), among children with severe pneumonia and hypoxemia, the risk of death was lower in the post-trial period than in the pre-trial (adjusted RR = 0.46, 95% CI = 0.37-0.58, p < 0.001), and the trial period (adjusted RR = 0.70, 95% CI = 0.51-0.95; p = 0.023). After the introduction of bCPAP oxygen therapy as part of the routine management of severe pneumonia and hypoxemia in the ICU of the Dhaka hospital, we observed significantly lower mortality, even after accounting for measurable confounding.

Clinical severity of Omicron and Delta SARS-CoV-2infections in children.

We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19). Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale. Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta. Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources.

Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19.

XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2 with high neutralizing activity. The safety and clinical efficacy of XAV-19 were investigated in patients with mild to moderate COVID-19. This phase II/III, multicentric, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in patients with a seven-point WHO score of 2 to 4 at randomization, i.e., inpatients with COVID-19 requiring or not requiring low-flow oxygen therapy, and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Adult patients presenting in specialized or emergency units with confirmed COVID-19 and giving their consent to participate in the study were randomized to receive 150 mg of XAV-19 or placebo. The primary endpoint was the proportion of patients with aggravation within 8 days after treatment, defined as a worsening of the seven-point WHO score of at least one point between day 8 and day 1 (inclusion). The neutralization activity of XAV-19 against variants circulating during the trial was tested in parallel. From March 2021 to October 2022, 279 patients received either XAV-19 (N = 140) or placebo (N = 139). A slow enrollment and a low rate of events forced the termination of the premature trial. XAV-19 was well tolerated. Underpowered statistics did not allow the detection of any difference in the primary endpoint between the two groups or in stratified groups. Interestingly, analysis of the time to improvement (secondary endpoint) showed that XAV-19 significantly accelerated the recovery for patients with a WHO score of 2 or 3 (median at 7 days vs. 14 days, p = 0.0159), and even more for patients with a WHO score of 2 (4 days vs. 14 days, p = 0.0003). The neutralizing activity against Omicron and BA.2, BA.2.12.1, BA.4/5, and BQ.1.1 subvariants was shown. In this randomized placebo- controlled trial with premature termination, reduction of aggravation by XAV-19 at day 8 in patients with COVID-19 was not detectable. However, a significant reduction of the time to improvement for patients not requiring oxygen was observed. XAV-19 maintained a neutralizing activity against SARS-CoV-2 variants. Altogether, these data support a possible therapeutic interest for patients with mild to moderate COVID-19 requiring anti-SARS-CoV-2 neutralizing antibodies. https://clinicaltrials.gov/, identifier NCT04928430; https://www.clinicaltrialsregister.eu/about.html (EudraCT), identifier 2020-005979-12.

FiO2 prediction formula during low flow oxygen therapy in an adult model: a bench study.

During low-flow oxygen therapy, the true value of inspired oxygen fraction (FiO2) is generally unknown. Knowledge of delivered FiO2 values may be useful as well as to adjust oxygen therapy, as well as to predict patient deterioration. This study proposes a New FiO2 Prediction Formula (NFiO2) for low-flow oxygenation and compares its predictive value to precedent formulas. In a bench study, the O2 Flow rate was delivered through a T-piece connected to a dual-compartment artificial lung controlled by a mechanical ventilator. To test the NFiO2 formula, a set of ventilatory parameters were tested: Tidal Volume was set from 400 to 600 ml, Respiratory Rate (RR) was set from 18 to 30 CPM, Ti/Ttot was set at 0.33 and 0.25, and O2 flow rates from 3 to 10L/min. A data acquisition system measured all parameters. To quantify the accuracy of the NFiO2 compared to other FiO2 prediction formulas, Bland and Altman agreement analyses were performed. To make use of the Duprez Formula 2018 in clinical practice, we simplified the formula to estimate the FiO2 during oxygenation at low flow. This NFiO2 formula makes use of only O2 Flow Rate and RR. Bias and limits of agreement between predicted FiO2 and benchtop FiO2 highlighted consistent differences between different FiO2 prediction formulas. The NFiO2 and the Duprez Formula 2018 seemed to be the most accurate formulas, followed by the Vincent Formula, and lastly the Shapiro Formula. A New FiO2 Prediction Formula was developed using clinical readily available variables (RR and O2 Flow rate) which showed good accuracy in predicting FiO2 during oxygenation at low flow.

Histologic Characteristics and Clinical Courses of Primary Viral Pneumonia Other than COVID-19.

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency. Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied. Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study. Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O2 treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI. Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O2 treatment was higher in SLI group than in those without SLI.

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial.

We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19). This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15. Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29. Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.

Experience in the use of remdesivir in patients with SARS-CoV-2 pneumonia

ObjectiveTo describe the effectiveness and safety of remdesivir in patients with SARS-CoV-2 pneumonia in real-world clinical practice conditions. MethodRetrospective observational study that included all adults with SARS-CoV-2 pneumonia admitted at the Moisés Broggi Hospital and treated with remdesivir between July 1st and November 7th, 2020. Efficacy outcomes were time to recovery, 28-day mortality, length of hospital stay, and the need of mechanical ventilation after treatment. The main safetyrelated endpoint was elevation of transaminases after treatment. ResultsA total of 111 patients were included of whom 97 (87.4%) were receiving low-flow oxygen therapy. Median time to recovery was 9 days [6-14]. Seven patients (6.3%) died at 28 days’ follow-up. Median length of hospital stay was 12 days [9-22] and 15 patients (13.5%) needed mechanical ventilation after treatment with remdesivir. Severe hypertransaminasemia was observed in 4 patients (4%). ConclusionsClinical outcomes of patients with SARS-CoV-2 pneumonia on low-flow oxygen therapy treated with remdesivir were similar to those published in clinical trials, both in terms of time to recovery and 28-day mortality.

Linear and non‑linear indices of vagal nerve in relation to sex and inflammation in patients with Covid‑19.

Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease-2019 (Covid-19). Low vagal neuro-immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid-19. A total of 19 patients with Covid-19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high-frequency HRV (HF-HRV), while non-linear parameters included 2 UV%. Immune/inflammatory parameters included C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF-HRV and RMSSD, are significantly negatively correlated with CRP and IL-6, independent of age. The non-linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high-flow nasal oxygen therapy had significantly higher IL-6 and CRP levels and lower levels of HF-HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low-flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non-linear vagal indexes of HRV and inflammatory markers in patients with Covid-19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid-19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid-19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid-19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid-19 patients by reducing the cytokine storm and excessive inflammation.