Comparison of Modified ROX Index Score and ROX Index Score for Early Prediction of High Flow Nasal Oxygen Therapy Outcome in Patients with Acute Respiratory Failure: A Prospective Observational Cohort Study.

Background: We compared the modified ROX index and ROX index scores in earlier predictions of high-flow nasal oxygen (HFNO) therapy outcomes in patients with acute respiratory failure. Methods: We conducted a prospective observational study on 151 acute respiratory failure patients initiated on HFNO therapy. The primary objective of this research was to compare the modified ROX index and ROX index to investigate which score predicted HFNO treatment outcome earlier. Results: The modified ROX index score had better predictive power than the ROX score at different time points, especially one hour following the start of HFNO therapy (AUC 0.790; 95% CI: 0.717-0.863; p < 0.001). For the ROX Index at 1 hour, the ideal cut-off value for HFNO outcome was 4.36 (sensitivity: 72.6%, specificity: 53.9%), and for the modified ROX index at 1 hour, it was 4.63 (sensitivity: 74.2%, specificity: 69.7%). The presence of various comorbidities didn't show any change in ROX-HR cut-off values. Conclusion: The modified ROX index is a better predictor of the success of HFNO therapy than the ROX index. Furthermore, the presence of any comorbidities did not affect modified ROX index cut-off values or the outcome of HFNO therapy. How to cite this article: Sarkar AG, Sharma A, Kothari N, Goyal S, Meshram T, Kumari K, et al. Comparison of Modified ROX Index Score and ROX Index Score for Early Prediction of High Flow Nasal Oxygen Therapy Outcome in Patients with Acute Respiratory Failure: A Prospective Observational Cohort Study. Indian J Crit Care Med 2024;28(9):842-846.

Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD.

BACKGROUND: Clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary outcomes and mortality between GLP-1 RA use and no use in patients with type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD). METHODS: The study identified 8060 matched GLP-1 RA users and non-users from Taiwan's National Health Insurance Research Database from 1 January 2008 to 31 December 2019. Cox proportional hazards models were used to determine the risk of cardiopulmonary outcomes between GLP-1 RA users and non-users. RESULTS: The mean follow-up time was 2.51 and 2.46 years for GLP-1 RA users and non-users, respectively. In the matched cohorts, GLP-1 RA users had a significantly lower risk of mortality (adjusted HR (aHR) 0.46, 95% CI 0.38 to 0.56), cardiovascular events (aHR 0.73, 95% CI 0.65 to 0.82), non-invasive positive pressure ventilation (aHR 0.66, 95% CI 0.47 to 0.93), invasive mechanical ventilation (aHR 0.64, 95% CI 0.51 to 0.8) and bacterial pneumonia (aHR 0.76, 95% CI 0.65 to 0.88) than GLP-1 RA non-users. The subsequent analyses for various subgroup and medication duration also showed that GLP-1 RA was associated with a significantly lower risk of mortality, cardiovascular events, ventilation support and bacterial pneumonia than non-GLP-1 RA. CONCLUSION: This nationwide cohort study showed that GLP-1 RA had a lower risk of cardiopulmonary outcomes and all-cause mortality than non-GLP-1 RA in patients with T2D and COPD. GLP-1 RA may help manage diabetes in people with COPD.

Prognostic efficacy of non-invasive ventilation in patients with overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea.

Background: Limited evidence exists regarding the effects of non-invasive ventilation (NIV) on the prognosis of patients with concomitant chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also known as overlap syndrome (OS). This study aimed to assess whether NIV alongside standard care could improve the prognosis of this cohort. Methods: We retrospectively collected data from 229 patients with severe OS treated in Beijing Anzhen Hospital between January 1, 2016 and January 1, 2020, with follow-up until December 1, 2023. All patients were recommended usual care and NIV and were subsequently divided into non-NIV (usual care only) and NIV groups (usual care plus NIV) per their willingness and adherence to NIV. Endpoints included all-cause and acute exacerbation of COPD (AECOPD)-associated death and re-hospitalization. Multivariate analyses were used to determine the relationship of NIV with prognosis. Results: The follow-up lasted for a median of 760 days (interquartile range, 245-1,374 days). Patients in the NIV group showed lower rates of all-cause (37.5% vs. 65.1%, P<0.001) and AECOPD-associated (31.7% vs. 58.7%, P<0.001) death compared with patients in the non-NIV group. Compared with usual care only, NIV treatment was associated with significant reduction in all-cause death [relative risks (RR) =0.459, 95% confidence interval (CI): 0.315-0.668, P<0.001], AECOPD-associated mortality (RR =0.424, 95% CI: 0.283-0.635, P<0.001), and re-hospitalization for all causes (RR =0.455, 95% CI: 0.342-0.605, P<0.001) and for AECOPD (RR =0.421, 95% CI: 0.308-0.575, P<0.001) in Cox hazards models, with significance persisting after multivariable adjustment. Conclusions: NIV may improve outcomes and survival in patients with severe OS of comorbid COPD and OSA. Confirmatory studies are needed to prove benefits.

Role of Non-invasive Ventilation (NIV) in Managing Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review.

Chronic obstructive pulmonary disease (COPD) is a significant global health issue that is characterized by airflow constriction and breathing difficulties. Non-invasive ventilation (NIV) is a recommended treatment for acute exacerbations of COPD (AECOPD), offering benefits over invasive mechanical ventilation (IMV). We aimed to evaluate the effectiveness, safety, and impact of NIV in managing AECOPD. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Medline, Cochrane Library, Embase, and Google Scholar for relevant studies published between 2015 and 2024. Inclusion criteria focused on studies involving AECOPD patients treated with NIV, including randomized controlled, cohort, and observational studies. We included 10 studies that fit our inclusion criteria for a thorough review. From the studies selected, NIV demonstrated significant reductions in mortality rates, intubation rates, and hospital stays compared to IMV. Albeit the need to train healthcare providers is essential, high adherence to NIV guidelines was observed. Different NIV modes showed comparable efficacy, and structured weaning protocols reduced relapse rates. NIV is a highly effective and safe treatment for patients with AECOPD than IMV. High-flow nasal therapy (HFNT) is a viable alternative for patients intolerant to NIV. Further research should standardize treatment protocols and optimize NIV use in clinical practice.

Effect of Sitting Baduanjin exercise on early rehabilitation of sepsis patients with non-invasive ventilation : a randomized controlled trial.

BACKGROUND: For patients with sepsis receiving non-invasive ventilation (NIV), early rehabilitation is crucial. The Sitting Baduanjin (SBE) is an efficient early rehabilitation exercise suitable for bed patients. There is no consensus about the effect of SBE on the early rehabilitation of septic patients with NIV. This study focused on how the SBE affected the early rehabilitation of sepsis patients with NIV. METHODS: 96 sepsis patients with NIV were randomly assigned to either an Baduanjin group that received the SBE based on the routine rehabilitation exercise (n = 48) or a control group (n = 48) that received routine rehabilitation exercise. The primary outcome was the Medical Research Council(MRC)score, and the Barthel Index score, the duration of NIV, length of ICU stay, length of total stay, hospitalization expense as secondary outcomes. RESULTS: A total of 245 sepsis patients were screened, with 96 randomly assigned. The study was completed by 90 patients out of the 96 participants.Results revealed that the MRC score increased in both groups, but the improvement of muscle strength in Baduanjin group was more obvious, with statistical significance (p < 0.001).There was statistically significantly difference between the two groups in Barthel Index at the day of transfer out of ICU(P = 0.028).The patients in the Baduanjin group had an average reduction of 24.09 h in the duration of NIV and 3.35 days in total length of hospital stay compared with the control group (p < 0.05).Of note, the Baduanjin group had significantly reduction the total hospitalization expense. No serious adverse events occurred during the intervention period. CONCLUSIONS: In patients with sepsis, the SBE appears to improve muscle strength and activities of daily living (ADL), and lowed the duration of NIV, the length of the total stay, and the hospitalization expense. TRIAL REGISTRATION: The study registered on the Chinese Clinical Trial Registry ( www.chictr.org.cn ), Clinical Trials identifier ChiCTR1800015011 (28/02/2018).

A Comprehensive Review on High-Flow Nasal Cannula Oxygen Therapy in Critical Care: Evidence-Based Insights and Future Directions.

High-flow nasal cannula (HFNC) therapy has emerged as a significant advancement in respiratory support, offering a non-invasive alternative to traditional oxygen delivery methods in critical care settings. This review comprehensively evaluates HFNC therapy, focusing on its definition, historical evolution, and current clinical applications. HFNC therapy delivers humidified and heated oxygen at high flow rates through a nasal cannula, enhancing oxygenation and patient comfort. The review highlights the physiological mechanisms underlying HFNC and its efficacy in managing acute respiratory failure, chronic obstructive pulmonary disease exacerbations, and postoperative respiratory support. Key findings from clinical trials and meta-analyses are discussed, emphasizing HFNC's advantages over conventional methods, such as reduced intubation rates and shorter ICU stays. The review also addresses safety considerations, including potential risks and complications associated with HFNC therapy. Furthermore, it explores future directions for research and technological advancements aimed at optimizing HFNC use in diverse patient populations. This review aims to provide evidence-based insights to inform clinical practice and guide future investigations in respiratory therapy.

Prophylactic non-invasive positive pressure ventilation reduces complications and length of hospital stay after invasive thoracic procedures: a systematic review.

QUESTION: In patients undergoing invasive thoracic procedures, what are the effects of prophylactic non-invasive positive pressure ventilation (NIV)? DESIGN: Systematic review with meta-analysis of randomised trials. Methodological quality was assessed using the PEDro scale and the certainty of evidence with the GRADE approach. PARTICIPANTS: Patients undergoing invasive thoracic procedures. INTERVENTION: Continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). OUTCOME MEASURES: Length of hospital stay, postoperative pulmonary complications, need for tracheal intubation, mortality, hypoxaemia, pulmonary function and adverse events. Meta-analysis was performed for all outcomes. Subgroup analyses estimated the effects of CPAP and BIPAP independently. RESULTS: Sixteen trials with 1,814 participants were included. The average quality of the included studies was fair. Moderate certainty evidence indicated that NIV reduces postoperative pulmonary complications (RD -0.09, 95% CI -0.15 to -0.04) without increasing the rate of adverse events (RD 0.01, 95% CI -0.02 to 0.04). Low certainty evidence indicated that NIV reduces length of hospital stay (MD -1.4 days, 95% CI -2.2 to -0.5) compared with usual care. The effects on intubation and mortality rates were very close to no effect, indicating that NIV is safe. Subgroup analyses showed that the evidence for CPAP had more precise estimates that that for BiPAP. CONCLUSION: NIV reduces postoperative pulmonary complications and length of stay after invasive chest procedures without increasing the risk of adverse events. REGISTRATION: PROSPERO CRD42015019004.

The Effect of Opioids and Benzodiazepines on Exacerbation Rate and Overall Survival in Patients with Chronic Obstructive Pulmonary Disease on Long-Term Non-Invasive Ventilation.

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0-5.0/ to 2.8/0.71-4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0-7.0/ to 3.5/1.2-5.5/) or opioids (3.0/2.0-6.0/ to 3.0/0.8-5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV.

An eight-year follow-up study of Home Invasive Mechanical Ventilation in Finland.

BACKGROUND: Studies on long-term invasive mechanical ventilation (IMV) via tracheostomy in chronic respiratory insufficiency are limited. The aim of this study was to clarify the use of HIMV (home invasive mechanical ventilation) within the Finnish population and to analyze the characteristics and survival rate of HIMV patients from 2015 to 2022. METHODS: Data on HIMV patients was collected annually from all Finnish Hospital District patient registries between January 1, 2015, and December 31, 2022. Data included basic demographic data of the patients, underlying diagnosis, time from diagnosis to HIMV initiation, treatment duration, and mortality. RESULTS: This study included 179 patients. In 2015, there were 107 HIMV patients, and as of December 31, 2022, there were 95 patients. During the eight-year follow-up period, 84 patients (46.9%) died and there were 67 new patients between 2015 and2022. The prevalence of HIMV treatment in Finland was 2.4/100,000 on January 1,2015, and 1.8/ 100 000 on December 31, 2022. The average number of years living with HIMV for deceased patients at death was 10.1 ± 10.5 years largely depending on the underlying diagnosis. Of all the HIMV treatments, 32% were elective. CONCLUSIONS: HIMV is a rare treatment in Finland, and based on our 8-year follow-up, prevalence of HIMV is diminishing. Given the high demands, and significant costs associated with HIMV, it is essential to prepare for long treatment, when planning HIMV. It is also advisable to prolong non-invasive ventilation (NIV) treatments for as long as possible.

Remifentanil vs. dexmedetomidine for cardiac surgery patients with noninvasive ventilation intolerance: a multicenter randomized controlled trial.

BACKGROUND: The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. METHODS: In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. RESULTS: A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3-3 vs. 3, IQR 3-4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35-8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8-12 days vs. 7.0 days, IQR 5-10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. CONCLUSIONS: In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

[Risk factors for initial non-invasive ventilation failure in very low birth weight infants with gestational age <32 weeks: a multicenter retrospective study]. / 胎龄<32å‘¨æžä½Žå‡ºç”Ÿä½“é‡å„¿åˆå§‹æ— åˆ›é€šæ°”å¤±è´¥çš„å½±å“å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation (NIV) failure in very low birth weight infants (VLBWI) with gestational age <32 weeks. METHODS: A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit (NICU) in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted. Based on the outcomes of initial NIV, the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis. RESULTS: A total of 817 infants were included, with 453 males (55.4%) and 139 failures (17.0%). The failure group had lower gestational age, birth weight, and 1-minute and 5-minute Apgar scores compared to the successful group (P<0.05). The failure group also had a higher proportion of respiratory distress syndrome (RDS) diagnosed upon NICU admission, higher maximum positive end-expiratory pressure during NIV, and higher percentages of reaching the required maximum fraction of inspired oxygen (FiO2) ≥30%, ≥35%, and ≥40% throughout the initial NIV process compared to the successful group (P<0.05). Gestational age (OR=0.671, 95%CI: 0.581-0.772), RDS (OR=1.955, 95%CI: 1.181-3.366), and FiO2 ≥30% (OR=2.053, 95%CI: 1.106-4.044) were identified as risk factors for initial NIV failure in these infants with gestational age <32 weeks (P<0.05). The failure group had higher incidences of complications such as pulmonary infections, pneumothorax, retinopathy of prematurity, moderate to severe bronchopulmonary dysplasia, and severe intraventricular hemorrhage during hospitalization, as well as longer hospital stays and higher total costs compared to the successful group (P<0.05). CONCLUSIONS: Smaller gestational age, a diagnosis of RDS in the NICU, and achieving a maximum FiO2 ≥30% during the initial NIV process are risk factors for initial NIV failure in infants with gestational age <32 weeks. Initial NIV failure significantly increases the risk of adverse outcomes in this population.

Phase-resolved MRI for measurement of pulmonary perfusion and ventilation defects in comparison with dynamic contrast-enhanced MRI and 129Xe MRI.

INTRODUCTION: This meta-analysis aims to evaluate the agreement and correlation between phase-resolved functional lung MRI (PREFUL MRI) and dynamic contrast-enhanced (DCE) MRI in evaluating perfusion defect percentage (QDP), as well as the agreement between PREFUL MRI and 129Xe MRI in assessing ventilation defect percentage (VDP). METHOD: A systematic search was conducted in the Medline, Embase and Cochrane Library databases to identify relevant studies comparing QDP and VDP measured by DCE MRI and 129Xe MRI compared with PREFUL MRI. Meta-analytical techniques were applied to calculate the pooled weighted bias, limits of agreement (LOA) and correlation coefficient. The publication bias was assessed using Egger's regression test, while heterogeneity was assessed using Cochran's Q test and Higgins I2 statistic. RESULTS: A total of 399 subjects from 10 studies were enrolled. The mean difference and LOA were -2.31% (-8.01% to 3.40%) for QDP and 0.34% (-4.94% to 5.62%) for VDP. The pooled correlations (95% CI) were 0.65 (0.55 to 0.73) for QDP and 0.72 (0.61 to 0.80) for VDP. Furthermore, both QDP and VDP showed a negative correlation with forced expiratory volume in 1 s (FEV1). The pooled correlation between QDP and FEV1 was -0.51 (-0.74 to -0.18), as well as between VDP and FEV1 was -0.60 (-0.73 to -0.44). CONCLUSIONS: PREFUL MRI is a promising imaging for the assessment of lung function, as it demonstrates satisfactory deviations and LOA when compared with DEC MRI and 129Xe MRI. PROSPERO REGISTRATION NUMBER: CRD42023430847.

Nutrition intake, muscle thickness, and recovery outcomes for critically ill patients requiring non-invasive forms of respiratory support: A prospective observational study.

BACKGROUND: Use of high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) in the intensive care unit (ICU) is increasing, yet reporting of nutrition intake, muscle thickness, or recovery outcomes in this population is limited. OBJECTIVE: The objective of this study was to quantify muscle thickness, nutrition intake, and functional recovery outcomes for patients receiving HFNC/NIV within the ICU. METHODS: A single-centre, prospective, observational study in adult ICU patients recruited within 48 hrs of commencing HFNC/NIV. Change in quadriceps muscle layer thickness using ultrasound (primary outcome) and 24 hr nutrition intake from study inclusion to day 7 (D7), functional capacity (Barthel Index), and quality of life (EuroQol five-dimension five-level utility index) at D90 were assessed. Data are n (%), mean ± standard deviation or median [interquartile range], are compared using paired sample t-test, and a P value of <0.05 was considered significant. RESULTS: Primary outcome data were available for n = 28/42: 64 ± 13 y, 61% male, body mass index: 29.1 ± 9.0 kg/m2, and Acute Physiology and Chronic Health Evaluation II score: 17 ± 5. Quadriceps muscle layer thickness reduced from 2.41 ± 0.87 to 2.12 ± 0.73 cm; mean difference: -0.29 cm (95% confidence interval: -0.44, -0.13). Nutrition intake increased from study inclusion to D7: 1735 ± 1283 to 5448 ± 2858 kJ and 17.4 ± 16.6 to 60.9 ± 36.8g protein. Barthel Index was 87 ± 20 at baseline and 91 ± 15 at D90 (out of 100). Quality of life was impaired at D90: 0.64 ± 0.23 (health = 1.0). CONCLUSION: Critically ill patients receiving HFNC/NIV experienced muscle loss and impaired quality of life.

A Phase I trial of Non-invasive Ventilation and seizure prophylaxis with levetiracetam In Children with Cerebral Malaria Trial (NOVICE-M Trial).

Background: African children with cerebral malaria and seizures caused Plasmodium falciparum are at greater risk of poor outcomes including death and neurological sequelae. The agonal events are severe hypoventilation and respiratory arrest often triggered by seizures. We hypothesised that prophylactic anti-seizure medication (ASM) could avert 'spikes' of intracranial pressure during or following seizures and that adequate ventilation could be supported by biphasic Cuirass Ventilation (BCV) which requires no intubation. Methods: A Phase I trial conducted in Kilifi, Kenya designed to provide data on safety, feasibility and preliminary data on seizure control using prophylactic ASM (levetiracetam) and BCV as non-invasive ventilatory support in children with cerebral malaria. Children aged 3 months to 12-years hospitalised with P falciparum malaria (positive rapid diagnostic test or a malaria slide), a Blantyre Coma Score ≤2 and a history of acute seizures in this illness are eligible for the trial. In a phased evaluation we will study i) BCV alone for respiratory support (n=10); ii) prophylactic LVT: 40mg/kg loading dose then 30mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10) and; iii) prophylactic LVT: 60mg/kg loading dose then 45mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10). Primary outcome measure: cumulative time with a clinically detected seizures or number of observed seizures over 36 hours. Secondary outcomes will be assessed by feasibility or ability to implement BCV, and recovery from coma within 36 hours. Safety endpoints include: aspiration during admission; death at 28 days and 180 days; and de-novo neurological impairments at 180 days. Conclusions: This is a Phase I trial largely designed to test the feasibility, tolerability and safety of using non-invasive ventilatory support and LVT prophylaxis in cerebral malaria. Registration: ISRCTN76942974 (5.02.2019); PACTR202112749708968 (20.12.2021).

Unfortunately, children with cerebral malaria continue to have very poor outcomes including severe hypoventilation and respiratory arrest (i.e. breathing is too slow or stops) during hospitalization which is often triggered by seizures. We will explore the potential benefits of a special type of ventilation that applies suction or negative pressure to the chest (meaning keeping children breathing by pushing air in and out of their lungs) in combination with anticonvulsants given before children have had any fits We will use a device called biphasic Cuirass Ventilation (BCV) that can be used by non-specialists to help children breath. BCV applies both negative and positive pressure to the chest, covering both inspiration (breathing in) and expiration (breathing out) phases of breathing, which is more appropriate for periods of when the breathing is too slow or stops for a period of time. We will also use an anticonvulsant drug, called levetiracetam to prevent seizures. It has been safely used in Malawian children and shown to improve outcomes. This will be given directly into the stomach via a nasogastric tube (tubes down the nose into the stomach) The study will be carried out at Kilifi County Hospital, Kenya and plans to enrol 30 children aged 3 months to 12 years with cerebral malaria and a positive malaria test The first ten children with have the BCV device only to assist respiration until they recover from their coma. The next twenty children in the trial will have the BCV device in addition with anticonvulsants given before children have had any fits as a preventive strategy to stop fits. All children will have regular monitoring during the period of coma/ventilation and will be followed up on days 28 and 180. The study aims to generate feasibility and safety data to support future trials.

Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear. METHODS: In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA). RESULTS: In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, PCM1 for the microtubule anchoring module, LIMS1 for the cell-substrate junction module. CONCLUSIONS: In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

Initiation of Chronic Non-invasive Ventilation.

Initiation of home non-invasive ventilation (NIV) requires careful consideration of the patient's condition, motivation, expectations, wishes, and social circumstances. The decision to start NIV depends on a combination of factors including patient symptoms and objective evidence of nocturnal hypoventilation. A solid understanding of the underlying pathophysiology is key to a systematic and well-balanced clinical approach to titrating NIV. The location where NIV is initiated is not the most relevant issue, provided that it is a comfortable, safe environment in which adequate monitoring can be assured. The majority of patients prefer their own home for treatment initiation.

Telemonitoring in Non-invasive Ventilation.

Telemonitoring in non-invasive ventilation is constantly evolving to enable follow-up of adults and children. Depending on the device and manufacturer, different ventilator variables are displayed on web-based platforms. However, high-granularity measurement is not always available remotely, which precludes breath-by-breath waveforms and precise monitoring of nocturnal gas exchange. Therefore, telemonitoring is mainly useful for monitoring utilization of the device, leaks, and respiratory events. Coordinated relationships between patients, homecare providers, and hospital teams are necessary to transform available data into diagnosis and actions. Telemonitoring is time and cost-consuming. The balance between cost, workload, and clinical benefit should be further evaluated.

The Role of High Flow Nasal Therapy in Chronic Respiratory Failure.

High-flow nasal therapy (HFNT) has an increasing role in the management of acute hypoxic respiratory failure. Due to its tolerable interface and ease of use, its role in chronic hypercapnic respiratory failure (CHRF) is emerging. This article examines the literature to date surrounding the short and long-term mechanisms of HFNT in sleep and wakefulness of CHRF patients. It is likely HFNT will have an increasing role in those patients intolerant of non-invasive ventilation.

Longitudinal Assessment of ROX and HACOR Scores to Predict Non-Invasive Ventilation Failure in Patients with SARS-CoV-2 Pneumonia.

Introduction: NIV (Non-invasive ventilation) and HFNC (High Flow nasal cannula) are being used in patients with acute respiratory failure. HACOR score has been exclusively calculated for patients on NIV, on other hand ROX index is being used for patients on HFNC. This is first study where ROX index has been used in patients on NIV to predict failure. Aim of the study: This study investigates the comparative diagnostic performance of HACOR score and ROX index to predict NIV failure. Methods: We performed a retrospective cohort study of non-invasively ventilated COVID-19 patients admitted between 1st April 2020 to 15th June 2021 to ICU of a tertiary care teaching hospital located in Central India. We assessed factors responsible for NIV failure, and whether these scores HACOR/ROX index have discriminative capacity to predict risk of invasive mechanical ventilation. Results: Of the 441 patients included in the current study, 179 (40.5%) recovered, while remaining 262 (59.4%) had NIV failure. On multivariable analysis, ROX index > 4.47 was found protective for NIV-failure (OR 0.15 (95% CI 0.03-0.23; p<0.001). Age > 60 years and SOFA score were other significant independent predictors of NIV-failure. The AUC for prediction of failure rises from 0.84 to 0.94 from day 1 to day 3 for ROX index and from 0.79 to 0.92 for HACOR score in the same period, hence ROX score was non-inferior to HACOR score in current study. DeLong's test for two correlated ROC curves had insignificant difference expect day-1 (D1: 0.03 to 0.08; p=3.191e-05, D2: -0.002 to 0.02; p = 0.2671, D3: -0.003 to 0.04; p= 0.1065). Conclusion: ROX score of 4.47 at day-3 consists of good discriminatory capacity to predict NIV failure. Considering its non-inferiority to HACOR score, the ROX score can be used in patients with acute respiratory failure who are on NIV.

Ventilation strategies in cardiogenic shock: Insights from the AltShock-2 registry.

AIMS: To describe the use and the relation to outcome of different ventilation strategies in a contemporary, large, prospective registry of cardiogenic shock patients. METHODS AND RESULTS: Among 657 patients enrolled from March 2020 to November 2023, 198 (30.1%) received oxygen therapy (OT), 96 (14.6%) underwent non-invasive ventilation (NIV), and 363 (55.3%) underwent invasive mechanical ventilation (iMV). Patients in the iMV group were significantly younger compared to those in the NIV and OT groups (63 vs. 69 years, p < 0.001). There were no significant differences between groups regarding cardiovascular risk factors. Patients with SCAI B and C were more frequently treated with OT and NIV compared to iMV (65.1% and 65.4% vs. 42.6%, respectively, p > 0.001), while the opposite trend was observed in SCAI D patients (12% and 12.2% vs. 30.9%, respectively, p < 0.001). All-cause mortality at 24 h did not differ amongst the three groups. The 60-day mortality rates were 40.2% for the iMV group, 26% for the OT group, and 29.3% for the NIV group (p = 0.005), even after excluding patients with cardiac arrest at presentation. In the multivariate analysis including SCAI stages, NIV was not associated with worse mortality compared to iMV (hazard ratio 1.97, 95% confidence interval 0.85-4.56), even in more severe SCAI stages such as D. CONCLUSIONS: Compared to previous studies, we observed a rising trend in the utilization of NIV among cardiogenic shock patients, irrespective of aetiology and SCAI stages. In this clinical scenario, NIV emerges as a safe option for appropriately selected patients.