Exploring Heterogeneity in Cost-Effectiveness Using Machine Learning Methods: A Case Study Using the FIRST-ABC Trial.

OBJECTIVE: The aim of this study was to explore heterogeneity in the cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with continuous positive airway pressure (CPAP) in children following extubation. DESIGN: Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the individual and subgroup levels using a causal forest approach, alongside a seemingly unrelated regression (SUR) approach for comparison. SETTINGS: FIRST-ABC is a noninferiority randomized controlled trial (ISRCTN60048867) including children in UK paediatric intensive care units, which compared HFNC with CPAP as the first-line mode of noninvasive respiratory support. PATIENTS: In the step-down FIRST-ABC, 600 children clinically assessed to require noninvasive respiratory support were randomly assigned to HFNC and CPAP groups with 1:1 treatment allocation ratio. In this analysis, 118 patients were excluded because they did not consent to accessing their medical records, did not consent to follow-up questionnaire or did not receive respiratory support. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study is the incremental net monetary benefit (INB) of HFNC compared with CPAP using a willingness-to-pay threshold of £20,000 per QALY gain. INB is calculated based on total costs and quality adjusted life years (QALYs) at 6 months. The findings suggest modest heterogeneity in cost-effectiveness of HFNC compared with CPAP at the subgroup level, while greater heterogeneity is detected at the individual level. CONCLUSIONS: The estimated overall INB of HFNC is smaller than the INB for patients with better baseline status suggesting that HFNC can be more cost-effective among less severely ill patients.

Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

Prognosis of mechanically ventilated patients with COVID-19 after failure of high-flow nasal cannula: a retrospective cohort study.

BACKGROUND: There is an argument whether the delayed intubation aggravate the respiratory failure in Acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). We aimed to investigate the effect of high-flow nasal cannula (HFNC) failure before mechanical ventilation on clinical outcomes in mechanically ventilated patients with COVID-19. METHODS: This retrospective cohort study included mechanically ventilated patients who were diagnosed with COVID-19 and admitted to the intensive care unit (ICU) between February 2020 and December 2021 at Asan Medical Center. The patients were divided into HFNC failure (HFNC-F) and mechanical ventilation (MV) groups according to the use of HFNC before MV. The primary outcome of this study was to compare the worst values of ventilator parameters from day 1 to day 3 after mechanical ventilation between the two groups. RESULTS: Overall, 158 mechanically ventilated patients with COVID-19 were included in this study: 107 patients (67.7%) in the HFNC-F group and 51 (32.3%) in the MV group. The two groups had similar profiles of ventilator parameter from day 1 to day 3 after mechanical ventilation, except of dynamic compliance on day 3 (28.38 mL/cmH2O in MV vs. 30.67 mL/H2O in HFNC-F, p = 0.032). In addition, the HFNC-F group (5.6%) had a lower rate of ECMO at 28 days than the MV group (17.6%), even after adjustment (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.83; p = 0.045). CONCLUSIONS: Among mechanically ventilated COVID-19 patients, HFNC failure before mechanical ventilation was not associated with deterioration of respiratory failure.

Bilevel positive airway pressure ventilation in patients susceptible to hypoxemia during procedural sedation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIMS: Hypoxemia is one of the most common adverse events during colonoscopy, particularly among patients who are diagnosed with obstructive sleep apnea (OSA) or are overweight. Consequently, the objective of this study was to evaluate the effectiveness of bilevel positive airway pressure (BPAP) ventilation for patients with high-risk hypoxemia during colonoscopy with sedation. METHODS: In this trial, 127 patients who met the eligibility criteria were randomly assigned to the BPAP oxygen group and nasal cannula (NC) group. The primary endpoint was the incidence of hypoxemia. RESULTS: Compared with the use of NC, BPAP ventilation exhibited a significant reduction in the incidence of hypoxemia, decreasing it from 23.8% to 6.3% (absolute risk difference, 17.5%; 95% confidence interval, 5.4-29.6; P = .006). Importantly, BPAP ventilation prevented the occurrence of severe hypoxemia (9.5% vs 0%; absolute risk difference, 9.5%; 95% confidence interval, 2.3-16.7; P = .035). In addition, the BPAP group required fewer airway interventions (P < .05). CONCLUSIONS: In individuals with OSA or overweight status, the use of BPAP ventilation during colonoscopy significantly reduced the incidence of hypoxemia. (Clinical trial registration number: ChiCTR2300073193.).

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

OBJECTIVE: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal. METHODS: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal. RESULTS: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080). CONCLUSION: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Utilization of immediate extubation in a multidisciplinary pathway for pediatric liver transplantation associated with improved postoperative outcomes.

BACKGROUND: Immediate extubation is becoming more common in liver transplantation. However, limited data exist on how to identify pediatric patients with potential for successful immediate extubation and how this intervention may affect recovery. METHODS: This retrospective review evaluated patients who underwent liver transplantation from 2015 to 2021 at Children's Healthcare of Atlanta. Preoperative status and intraoperative management were evaluated and compared. Outcomes comprised thrombosis, surgical reexploration, retransplantation, as well as reintubation, high flow nasal cannula (HFNC) usage, postoperative infection, the length of stay (LOS), and mortality. RESULTS: A total of 173 patients were analyzed, with 121 patients (69.9%) extubated immediately. The extubation group had older age (median 4.0 vs 1.25 years, p = .048), lower PELD/MELD (28 vs. 34, p = .03), decreased transfusion (10.2 vs. 41.7 mL/kg, p < .001), shorter surgical time (332 vs. 392 min, p < .001), and primary abdominal closure (81% vs. 40.4%, p < .001). Immediate extubation was associated with decreased HFNC (0.21 vs. 0.71 days, p = .02), postoperative infection (9.9% vs. 26.9%, p = .007), mortality (0% vs. 5.8%, p = .036), and pediatric intensive care unit LOS (4.7 vs. 11.4 days, p < .001). The complication rate was lower in the extubation group (24.8% vs. 36.5%), but not statistically significant. CONCLUSIONS: Approximately 70% of patients were able to be successfully extubated immediately, with only 2.5% requiring reintubation. Those immediately extubated had decreased need for HFNC, lower infection rates, shorter LOS, and decreased mortality. Our results show that with proper patient selection and a multidisciplinary approach, immediate extubation allows for improved recovery without increased respiratory complications after pediatric liver transplantation.

High-flow nasal cannula use in pediatric patients for other indications than acute bronchiolitis-a scoping review of randomized controlled trials.

The objective of the study is to summarize current literature on high-flow nasal cannula (HFNC) use for different indications in pediatric patient excluding acute bronchiolitis and neonatal care. The study design is a systematic scoping review. Pubmed, Scopus, and Web of Science databases were searched in February, 2023. All abstracts and full texts were screened by two independent reviewers. Randomized controlled trials focusing on HFNC use in pediatric patients (age < 18 years) were included. Studies focusing on acute bronchiolitis and neonatal respiratory conditions were excluded. Study quality was assessed by Cochrane risk of bias 2.0 tool. The main outcomes are patient groups and indications, key outcomes, and risk of bias. After screening 1276 abstracts, we included 22 full reports. Risk of bias was low in 11 and high in 5 studies. We identified three patient groups where HFNC has been studied: first, children requiring primary respiratory support for acute respiratory failure; second, perioperative use for either intraprocedural oxygenation or postoperative respiratory support; and third, post-extubation care in pediatric intensive care for other than postoperative patients. Clinical and laboratory parameters were assessed as key outcomes. None of the studies analyzed cost-effectiveness.Conclusion: This systematic scoping review provides an overview of current evidence for HFNC use in pediatric patients. Future studies should aim for better quality and include economic evaluation with cost-effectiveness analysis.Protocol registration: Protocol has been published https://osf.io/a3y46/ .

Dyspnoea relief as an inherent benefit of high flow nasal cannula therapy: A laboratory randomized trial in healthy humans.

BACKGROUND AND OBJECTIVE: Persistent dyspnoea is a public health issue for which the therapeutic arsenal is limited. This study tested high-flow nasal cannula therapy (HFNT) as a means to alleviate experimental dyspnoea. METHODS: Thirty-two healthy subjects underwent an experimental dyspnoea induced by thoracoabdominal elastic loading. HFNT was administered with alternately FiO2 of 100% (HFNT100) or 21% (HFNT21). The sensory (S-VAS) and affective (A-VAS) components of dyspnoea, transcutaneous CO2 pressure (PtcCO2 ), pulse-oximetry oxygen saturation (SpO2 ), heart rate, respiratory rate and skin galvanometry were monitored continuously. Three experimental sessions of 8 min were conducted: the first session consisted in familiarization with the experimental dyspnoea and the next two sessions tested the effects of HFNT100 and HFNT21 alternatively in a randomized order. RESULTS: HFNT21 and HFNT100 significantly reduced dyspnoea, respectively of ∆A-VAS = 0.80 cm [-0.02-1.5]; p = 0.007 and ∆A-VAS = 1.00 cm [0.08-1.75]; p < 0.0001; ∆S-VAS = 0.70 cm [-0.15-1.98]), p < 0.0001 and ∆S-VAS = 0.70 cm [0.08-1.95]), p = 0.0002) with no significant difference between HFNT21 and HFNT100. HFNT did not significantly alter the respiratory rate or the heart rate, reduced PtcCO2 only on room air and GSR under both experimental conditions. CONCLUSION: HFNT was associated with a statistically significant reduction in the intensity of the sensory and affective components of dyspnoea, independent of oxygen addition. This relief of laboratory dyspnoea could result from a reduction of afferent-reafferent mismatch.

High-Flow Nasal Oxygen versus Conventional Nasal Cannula in Preventing Hypoxemia in Elderly Patients Undergoing Gastroscopy with Sedation: A Randomized Controlled Trial.

Background: We aimed to compare the prevention of hypoxemia using High-flow nasal oxygen (HFNO) or regular nasal tubing (CNC) in elderly patients undergoing gastroscopy with sedation. Methods: This study was a prospective, randomized, controlled trial conducted at a single center. We included elective patients aged 65 and above who were undergoing gastroscopy with sedation. In the intervention group (HFNO), we set the oxygen flow rate to 60 liters per minute with an oxygen fraction (FiO2) of 0.6, while in the control group (CNC), it was 6 liters per minute. The primary outcome was the occurrence of hypoxemia (defined as Spo2 < 90%). Results: A total of 125 participants were enrolled (HFNO group: n = 63; CNC group: n = 62). The occurrence of hypoxemia was found to be significantly lower in the HFNO group compared to the CNC group (3.2% vs. 22.6%, p = 0.001). Additionally, a significantly shorter duration of low oxygen levels was observed in the HFNO group [0.0 seconds (0.0-13.0)] compared to the CNC group [0.0 seconds (0.0-124.0), p<0.001]. Moreover, a higher minimum Spo2 value was achieved in the HFNO group [99.0% (98.0-100.0) vs. 96.5% (91.0-99.0), p < 0.001], and a shorter recovery time was recorded [0.5 minutes (0.0-0.5) vs. 0.5 minutes (0.0-1.0), p = 0.016] in comparison to the CNC group. There were no differences in terms of comfort level [0 (0-4) vs. 0 (0-5), p = 0.268] between the two groups. Conclusions: The HFNO system was determined to be a safe and highly effective method for oxygen delivery, leading to a reduction in the occurrence of hypoxemia in elderly patients undergoing gastroscopy with sedation. It is recommended that HFNO be considered as the standard approach for management in this population.

Continuous positive airway pressure versus high-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear. METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days. RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events. CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

Enhancing exercise tolerance in interstitial lung disease with high-flow nasal cannula oxygen therapy: A randomized crossover trial.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is characterized by dyspnoea on exertion and exercise-induced hypoxaemia. High-flow nasal cannula (HFNC) therapy reduces the respiratory workload through higher gas flow and oxygen supplementation, which may affect exercise tolerance. This study aimed to examine the effects of oxygen and gas flow rates through HFNC therapy on exercise tolerance in ILD patients. METHODS: We conducted three-treatment crossover study. All ILD patients performed the exercises on room air (ROOM AIR setting: flow, 0 L/min; fraction of inspired oxygen [FiO2], 0.21), HFNC (FLOW setting: flow 40 L/min, FiO2 0.21), and HFNC with oxygen supplementation (FLOW + OXYGEN setting: flow 40 L/min, FiO2 0.6). The primary endpoint was the endurance time, measured using constant-load cycle ergometry exercise testing at a peak work rate of 80%. RESULTS: Twenty-five participants (10 men, 71.2 ± 6.7 years) were enrolled. The increase in exercise duration between the ROOM AIR and FLOW was 46.3 s (95% CI, -6.1 to 98.7; p = 0.083), and the FLOW and FLOW + OXYGEN was 91.5 s (39.1-143.9; p < 0.001). The percutaneous oxygen saturation (SpO2) at rest was significantly higher with the FLOW + OXYGEN setting than with the ROOM AIR and FLOW settings, and the difference persisted during exercise. At equivalent time points during exercise, the SpO2 with the FLOW setting was significantly higher than that with the ROOM AIR setting. CONCLUSION: Oxygen supplementation in HFNC therapy improved exercise tolerance and SpO2. We found that gas flow alone did not improve exercise tolerance, but improved SpO2 during exercise.

Exteriorization of the uterus reduces fetoscopic cannula-induced stress and strain: A finite element model analysis.

OBJECTIVE: To estimate stresses and strains in the uterine wall and fetal membranes with single/multi-port fetoscopy, simulating either a percutaneous access or via exteriorized uterus. STUDY DESIGN: Finite element models based on anatomical dimensions, material properties and boundary conditions were created to simulate stresses, strains and displacements on the uterine wall and fetal membranes during simulated fetal surgery either via exteriorized uterus or percutaneous approach, and with one or three cannulas. Clinically, we measured the anatomical layer thickness and cannula entry point displacement in patients undergoing single port percutaneous fetoscopy. RESULTS: Simulations demonstrate that single port percutaneous fetoscopy increases stress on the fetal membranes (+105%, 128 to 262 kPa) and uterine wall (+115%, 0.89 to 1.9 kPa) compared to exteriorized uterine access. Using three ports increases stress by 110% (148 to 312 kPa) on membranes and 113% (1.08 to 2.3 kPa) on uterine wall. Finite Element Method showed 0.75 cm uterine entry point displacement from the cutaneous entry, while clinical measurements demonstrated displacement of more than double (1.69 ± 0.58 cm), suggesting modeled measurements may be underestimations. CONCLUSION: The stresses and strains on the fetal membranes and uterus are double as high when entering percutaneously than via an exteriorized uterus. Based on what can be clinically measured, this may be an underestimation.

High-flow nasal cannula therapy for infants with bronchiolitis.

BACKGROUND: 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. OBJECTIVES: To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Impact of cannula diameter on pregnancy outcomes after minimally invasive fetal laser surgery in the treatment of twin-to-twin transfusion syndrome: A systematic review and meta-analysis.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) remains a major complication of fetal laser surgery in the treatment of twin-to-twin transfusion syndrome (TTTS). The aim of the study was to determine the impact of cannula size on pregnancy outcomes, with a particular focus on PPROM. MATERIAL AND METHODS: The protocol was developed and registered in the PROSPERO database under registration number CRD42022333630. The PubMed, Web of Science, and EMBASE databases were searched electronically on May 18, 2022, and updated on March 2, 2023, utilizing a combination of the relevant MeSH terms, keywords, and word variants for "TTTS" and "laser". Randomized controlled trials, prospective and retrospective cohorts, case-control studies, and case reports/series with more than five participants were considered eligible for inclusion. Studies reporting the cannula diameter and PPROM rate after laser surgery in the treatment of monochorionic pregnancies affected by TTTS between 16- and 26 weeks' gestation were included. Data was extracted independently, and when appropriate, a random-effects meta-analysis was undertaken to calculate pooled estimates and their confidence intervals. Heterogeneity in the effect estimates of the individual studies was calculated using the I2 statistic. The primary outcome was PPROM rate. Secondary outcomes were survival rate, preterm birth, and incomplete surgery. The quality of the included studies was assessed using a modified quality in prognosis study tool. RESULTS: We included a total of 22 studies, consisting of 3426 patients. Only one study was scored as low quality, seven as moderate quality, and the remaining 14 as high quality. The mean PPROM rate after laser surgery treating TTTS was 22.9%, ranging from 11.6% for 9 French (Fr) to 54.0% for 12 Fr. Subsequent meta-regression for the clinically relevant PPROM rate before 34 weeks of gestation, showed increased PPROM rates for increased cannula size (p-value 0.01). CONCLUSIONS: This systematic review confirmed PPROM as a frequent complication of fetal laser surgery, with a mean PPROM rate of 22.9%. A larger cannula diameter relates to a significant higher PPROM risk for PPROM before 34 weeks gestation. Hence, the ideal balance between optimal visualization requiring larger port diameters and shorter operation time and more complete procedures that benefit from larger diameters is crucial to reduce iatrogenic PPROM rates.

Effect of Nasal Continuous Positive Airway Pressure on Retinopathy of Prematurity in Preterm Newborns: A Comparative Analysis with Mechanical Ventilation and High-Flow Nasal Cannula Therapy.

BACKGROUND Retinopathy of prematurity (ROP), originally described as retrolental fibroplasia, represents an abnormal growth of blood vessels in the premature retina that can occur in response to oxygen therapy. The association between ROP and invasive mechanical ventilation has been widely studied in the literature; however, the relationships between different types of ventilation and ROP have not been as well documented. This study aimed to compare the association of ROP incidence with mechanical ventilation (MV), nasal continuous positive airway pressure (nCPAP), and high-flow nasal cannula (HFNC) therapies in 130 pre-term infants with gestational ages <32 weeks. MATERIAL AND METHODS The study includes 130 premature newborns, out of which 54 underwent MV therapy, either alone or in combination with nCPAP or HFNC therapy, 63 underwent nCPAP therapy, either alone or in combination with MV or HFNC therapy, and 23 underwent HFNC therapy, either alone or in combination with MV or nCPAP therapy. The relationships between ROP and the 3 types of ventilation were analyzed by univariate followed by multivariate logistic regression. RESULTS When adjusting for covariates, only nCPAP and birth weight were significantly associated with ROP, the former being a strong risk factor, with an adjusted odds ratio (AOR) of 7.264 (95% CI, 2.622-20.120; P<0.001), and the latter being a weak protective factor, with an AOR of 0.998 (95% CI, 0.996-0.999; P<0.05). CONCLUSIONS The results showed nCPAP was a strong ROP risk factor, birth weight was a weak ROP protective factor, and MV and HFNC were not significantly associated with increased ROP risk.

Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57-0.96) or Asian (OR, 0.6; 95% CrI, 0.35-0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.

Association of Noninvasive Respiratory Support with Extubation Outcomes in Brain-injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of the ENIO Prospective Observational Study.

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

Oral enteral nutrition in the emergency department for children with bronchiolitis hospitalized on high flow nasal cannula.

OBJECTIVES: We assessed whether initiation of oral enteral nutrition in the emergency department (ED) for patients with bronchiolitis hospitalized on humidified high flow nasal cannula (HHFNC) was associated with a shorter hospital length of stay (LOS) without an increase in return ED visits or hospital readmissions. PATIENTS AND METHODS: This retrospective cohort study included children ≤24 months of age with bronchiolitis hospitalized to the general pediatric floor on HHFNC in two time periods: October 1, 2018 - April 30, 2019, and following implementation of a revised institutional bronchiolitis pathway that encouraged enteral nutrition initiation in the ED, October 1, 2021 - April 30, 2022. The primary outcome of interest was hospital LOS where the exposure was enteral feeding in the ED. RESULTS: We included 391 'fed', 114 'not fed' and 304 'unknown' patients. HHFNC treatment time (25 h for 'fed' vs. 43 h for 'not fed' vs. 35 h for'unknown', p = 0.0001) and hospital LOS (39 h for 'fed' vs. 56 h for 'not fed' vs. 48 h for 'unknown', p = 0.0001) was shorter in the 'fed' group. There were no significant differences in return ED visits or hospital readmissions. Using our median LOS (45.1 h, inter-quartile range 30.2, 64.4 h) while controlling for age, sex, initial HHFNC flow rate, the respiratory oxygenation (ROX) index, viral etiology, and time period, an adjusted logistic regression analysis demonstrated that patients fed in the ED were 1.8 times more likely to have a hospital LOS of <45 h (aOR 1.88, 95% CI 1.11-3.18, p = 0.019). CONCLUSIONS: Initiation of oral enteral nutrition in the ED for patients with bronchiolitis on HHFNC is associated with a shorter hospital LOS without an increase in return ED visits or hospital readmissions. Future prospective studies are needed to develop feeding recommendations for children with bronchiolitis receiving HHFNC support.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.