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Conclusions
coronary artery lesions, CKD
CARDIAC DEATH
In patients with complex coronary artery lesions, intravascular imaging–guided PCI was superior to angiography-guided PCI in reducing the risk of a composite of cardiac death, target vessel–related MI, or target vessel revascularization in both the CKD and the non-CKD population. The benefit was more apparent in the CK...
PMC10687657
Background
depressive disorder, depressive, MDD
DISORDER
Major depressive disorder (MDD) is the most prevalent mental health disorder worldwide, including among U.S. service members. In addition to evidence-based treatments, activity-based approaches have been shown to effectively treat depressive symptoms, particularly when they occur in the natural environment.
PMC9936467
Methods
MDD, depression, depression/anxiety
This study compared two activity-based interventions, Surf Therapy and Hike Therapy, on depression outcomes among 96 active duty service members with MDD. Participants were randomized to 6 weeks of Surf or Hike Therapy. Clinician-administered and self-report measures were completed at preprogram, postprogram, and 3-mon...
PMC9936467
Results
depression
Multilevel modeling results showed that continuous depression outcomes changed significantly over time (
PMC9936467
Limitations
The sample consisted of service members, so results may not generalize to other populations. Most participants received concurrent psychotherapy or pharmacotherapy, and, although statistically accounted for, results should be interpreted in this context.
PMC9936467
Conclusions
MDD
Both Surf and Hike Therapies appear to be effective adjunctive interventions for service members with MDD. Research is needed to examine the effectiveness of these therapies as standalone interventions.
PMC9936467
Trial registration
Clinical trials registration numberNCT03302611; First registered on 05/10/2017.
PMC9936467
Supplementary Information
The online version contains supplementary material available at 10.1186/s12888-022-04452-7.
PMC9936467
Keywords
PMC9936467
Introduction
depressive disorder, MDD, depressive symptoms
DISORDER
Major depressive disorder (MDD) is a prevailing mental health disorder, including among U.S. service members [Fortunately, existing evidence-based treatments, such as cognitive behavioral therapy and antidepressant medications, are efficacious in treating MDD [Given the variability in treatment tolerance and response [...
PMC9936467
Methods
PMC9936467
Participants
Participants included 110 active duty service members referred to the Wounded, Ill, and Injured (WII) Wellness Program at Naval Medical Center San Diego (NMCSD) between January 2018 and March 2020 (see CONSORT diagram; Fig. CONSORT flowchart of participants. Intervention “completion,” as determined by the NMCSD Surf an...
PMC9936467
Program
The Surf and Hike Therapy programs are provided as an option of standard care at NMCSD. Both programs consisted of six consecutive weekly sessions, each lasting 3 to 4 hours. In this study, the programs used a cohort format accommodating approximately 20 service members per cycle. The Surf Therapy program occurred at a...
PMC9936467
Procedure
MDD
SECONDARY, BLIND
Participants were assessed at preprogram, postprogram, 3-month follow-up, and within each session. All participants completed a preprogram assessment that included clinical interview and self-report measures evaluating MDD and related symptoms, after which they were assigned a randomized condition if eligible for study...
PMC9936467
Measures
depression, depressive
Preprogram measures included participant demographics, service characteristics, concurrent treatment utilization (i.e., psychotherapy or pharmacotherapy for depression), depressive symptoms, and physical activity. Preprogram physical activity was assessed with the 7-item International Physical Activity Questionnaire-Sh...
PMC9936467
Depression measures
depression, Depression
The primary outcome measure was the Montgomery–Åsberg Depression Rating Scale (MADRS) [Self-reported depression severity was assessed with the 9-item Patient Health Questionnaire (PHQ-9) [
PMC9936467
Participant satisfaction
Participant satisfaction with each program was assessed with the 8-item Client Satisfaction Questionnaire (CSQ-8) [
PMC9936467
Assessment reliability
The MINI and MADRS were audio-recorded across time points. Twenty percent of participants (
PMC9936467
Data analysis
depression
SESSION
Data were analyzed as intent-to-treat; therefore, all service members eligible for study participation (Both longitudinal (preprogram, postprogram, 3-month follow-up) and within session (presession, postsession) analyses were conducted with MLM using a step-up model building process. Logical covariance matrices were co...
PMC9936467
Results
Study sample characteristics are displayed in Table Preprogram sample characteristics *
PMC9936467
Piecewise longitudinal analyses
APPENDIX
Piecewise longitudinal analyses were conducted from pre- to postprogram and again from postprogram to 3-month follow-up. Means and standard deviations for outcome variables are in Appendix
PMC9936467
Final MADRS models
Depression
Final MLM results for the MADRS are featured in Table Estimates of fixed effects of final multilevel models examining MADRS over time Pharmacotherapy and psychotherapy use is relative to each time point and was used as a predictor; for pre- to postprogram, preprogram usage was utilized; for postprogram to follow-up, po...
PMC9936467
Final PHQ-9 models
Final MLM results for the PHQ-9 are shown in Table Estimates of fixed effects of final multilevel models examining PHQ-9 over time Pharmacotherapy and psychotherapy use is relative to each time point and used as a predictor; for pre- to postprogram, preprogram usage was utilized; for postprogram to follow-up, postprogr...
PMC9936467
Diagnostic outcomes
MDD
At postprogram, participants in both interventions showed significant within-group changes in rates of MDD diagnosis using McNemar’s test (
PMC9936467
Within-session analyses
APPENDIX
Means and standard deviations for PHQ-4 scores can be found in Appendix The final pre- to postsession model for the PHQ-4 is shown in Table Estimates of fixed effects of final multilevel models examining PHQ-4 over time
PMC9936467
Discussion
MDD, depressive, depression, depression/anxiety
REMISSION
The growing interest in exercise and adjunctive interventions for MDD calls for rigorous evaluation to determine their efficacy. Surf therapy and blue space have received theoretical and practical consideration as an adjunctive intervention for psychological symptoms in military populations [In addition to the lasting ...
PMC9936467
Conclusions
Activity-based therapies provide individuals with the opportunity to exercise, socialize, engage with the natural environment, and experience respite from their psychological symptoms [
PMC9936467
Disclaimer
KHW, KTKE, and BMK are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17, U.S.C. §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C. §101 defines a U.S. Government work as work prepared by a mil...
PMC9936467
Authors’ contributions
RECRUITMENT
KHW: Secured Funding; Conceptualization, Methodology, Investigation, Resources, Writing – Original Draft, Supervision, Project Administration. NPO: Conceptualization, Methodology, Formal Analysis, Writing – Original Draft, Data Curation, Project Management. TNR: Writing - Original Draft. LHG: Investigation, Data Curati...
PMC9936467
Funding
This work was supported by the U.S. Navy Bureau of Medicine and Surgery (BUMED) under work unit no. N1600. BUMED had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.
PMC9936467
Availability of data and materials
The protocol and datasets generated and/or analyzed during the current study are not publicly available due to security protocols and privacy regulations, but they may be made available on reasonable request by the Naval Medical Center San Diego or Naval Health Research Center IRBs (contact phone + 1.619.553.8400) or b...
PMC9936467
Declarations
PMC9936467
Ethics approval and consent to participate
The study protocol was approved by the Naval Medical Center San Diego Institutional Review Board in compliance with all applicable Federal regulations governing the protection of human subjects (protocol: NMCSD.2017.0007). Written informed consent was obtained from all participants involved in the study, and participat...
PMC9936467
Consent for publication
Not applicable.
PMC9936467
Competing interests
SECONDARY
Spouse of the first author is an employee of Google LLC and has stock options as part of compensation package. Google LLC owns Fitbit products, which were used in the study for secondary data collection. Fitbit data are not reported in the current manuscript. When published, results are not expected to affect the value...
PMC9936467
References
PMC9936467
Supplementary Information
The Agent device consists of a semi-compliant balloon catheter, which is coated with a therapeutic low-dose formulation of paclitaxel (2 µg/mmThe online version contains supplementary material available at 10.1007/s12928-023-00953-8.
PMC10764532
Keywords
PMC10764532
Introduction
CAD, vessel coronary lesions
CORONARY ARTERY DISEASE, CAD
Patients with coronary artery disease (CAD) have three common therapeutic options: (1) medical therapy and risk factor modification, (2) coronary artery bypass graft surgery (CABG) and (3) percutaneous coronary intervention (PCI). As PCI technology and revascularization procedures evolved, balloon angioplasty, bare met...
PMC10764532
Methods
PMC10764532
Study design
AGENT Japan, a prospective, single-blind, non-inferiority study, randomized patients with SVD to receive either Agent or SeQuent Please in a 2:1 fashion. This trial also includes a single-arm substudy that evaluates the safety and effectiveness of Agent in patients with ISR of a previously treated lesion.This study was...
PMC10764532
Study end points
restenosis, ischemia-driven, stenosis
MYOCARDIAL INFARCTION, ENLARGEMENT, CARDIAC DEATH, MLD, RESTENOSIS, STENOSIS
The SV RCT primary end point was a non-inferiority comparison of Agent and SeQuent Please for the rate of TLF at 6 months (ischemia-driven revascularization of the target lesion [TLR], myocardial infarction [MI; Q-wave and non–Q-wave] related to the target vessel or cardiac death) [Quantitative coronary analysis (QCA) ...
PMC10764532
Statistical analysis
SD
Discrete variables were reported as percentages (%), and differences were assessed using Chi-squared or Fisher’s exact tests. Continuous variables were calculated as the mean ± SD and compared using Student’s
PMC10764532
Results
PMC10764532
Angiographic follow-up
Angiographic follow-up was performed after 6 months for all patients except 2 in the Agent arm and 1 in the SeQuent Please arm (follow-up rates 98% and 98% in Agent and SeQuent Please arms, respectively). Baseline, post-procedural lesions, and 6 months angiographic follow-up, quantified by coronary angiography, reveale...
PMC10764532
AGENT Japan ISR substudy
A total of 30 patients were enrolled in the ISR substudy at nine sites in Japan. One-year follow-up was available in 29 (97%) patients treated with the Agent DCB (Fig. 
PMC10764532
Angiographic follow-up
Angiographic follow-up was performed at 6 months in all but one patient (follow-up rate 97%). Quantitative coronary angiographic lesion characteristics and 6 months angiographic follow-up are shown in Table
PMC10764532
Clinical events
As reported previously, the primary end point of 6-month TLF was observed in 3.3% of Agent-treated patients, which was significantly less than the study success criterion of 15.1% (1-sided 97.5% UCB: 9.8%,
PMC10764532
Discussion
thrombosis, bleeding, anxiety/depression, angioplasty, fracture, impingement, CAD, atherosclerotic CAD, Restenosis, restenosis
THROMBOSIS, BLEEDING, PROLIFERATION, EVENT, CARDIAC DEATH, COMPLICATIONS, RESTENOSIS, RESTENOSIS, CAD
The AGENT Japan study represents the first clinical trial comparing Agent and SeQuent Please DCBs with two different drug formulations in Japanese patients. The principal findings through 1 year include: (1) relatively comparable TLF rates between arms; (2) no significant differences in the rates of individual componen...
PMC10764532
Study limitations
EVENTS
45 treated cases counted toward technical failure based on the definition of angiographic success. Of these, two patients in the Agent arm underwent TVR (195 days after the index procedure) and TLR (228 days after the index procedure). None of the 11 patients in the SeQuent Please group experienced events related to th...
PMC10764532
Conclusions
AGENT Japan is the first randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 μg/mm
PMC10764532
Acknowledgements
The authors thank Pooja Bhatt, Ph.D. (Boston Scientific Corporation), and Sachiyo Sato (Boston Scientific Japan K.K.) for assistance in manuscript preparation and trial management.
PMC10764532
Data availability
The deidentified participant data for this clinical trial will not be shared.
PMC10764532
Declarations
PMC10764532
Conflict of interest
The AGENT Japan trial was sponsored and funded by BSC Japan K.K. Dr. Ando received honoraria from Terumo, Japan Lifeline, Bristol Myers Squibb, Japan Medtronic, Abbott Medical Japan and Biotronik Japan. Dr. Shite received honoraria from Abbott, Terumo and Nipro. Dr. Ken Kozuma received the honoraria and research and sc...
PMC10764532
References
PMC10764532
Key Points
PMC9857319
Question
early-stage ERBB2/HER2-positive
BREAST CANCER
Which immune-related biomarker provides the most valuable information to predict pathologic complete response and event-free survival in patients with early-stage ERBB2/HER2-positive breast cancer: tumor-infiltrating lymphocytes, immune-related gene expression signatures, or both?
PMC9857319
Findings
early-stage ERBB2/HER2-positive
BREAST CANCER
In this predictive prognostic study in which a combined correlative analysis of the CALGB 40601 and PAMELA trials was conducted, 305 patients with early-stage ERBB2/HER2-positive breast cancer, 6 B-cell–related signatures were more strongly associated with pathologic complete response than were tumor-infiltrating lymph...
PMC9857319
Meaning
Findings suggest that when both tumor-infiltrating lymphocytes and gene expression are available, the prognostic and predictive value of RNA sequencing–based immune signatures is superior.
PMC9857319
Importance
early-stage ERBB2/HER2-positive
BREAST CANCER
Both tumor-infiltrating lymphocytes (TILs) assessment and immune-related gene expression signatures by RNA profiling predict higher pathologic complete response (pCR) and improved event-free survival (EFS) in patients with early-stage ERBB2/HER2-positive breast cancer. However, whether these 2 measures of immune activa...
PMC9857319
Objective
early-stage ERBB2/HER2-positive, breast cancer
BREAST CANCER
To examine the prognostic ability of TILs and immune-related gene expression signatures, alone and in combination, to predict pCR and EFS in patients with early-stage ERBB2/HER2-positive breast cancer treated in 2 clinical trials.
PMC9857319
Design, Setting, and Participants
Leukemia, Cancer
GROUP B, SECONDARY, LEUKEMIA, CANCER
In this prognostic study, a correlative analysis was performed on the Cancer and Leukemia Group B (CALGB) 40601 trial and the PAMELA trial. In the CALGB 40601 trial, 305 patients were randomly assigned to weekly paclitaxel with trastuzumab, lapatinib, or both for 16 weeks. The primary end point was pCR, with a secondar...
PMC9857319
Main Outcomes and Measures
tumors
REGRESSION, TUMORS
Immune-related gene expression profiling by RNA sequencing and TILs were assessed on 230 CALGB 40601 trial pretreatment tumors and 138 PAMELA trial pretreatment tumors. The association of these biomarkers with pCR (CALGB 40601 and PAMELA) and EFS (CALGB 40601) was studied by logistic regression and Cox analyses.
PMC9857319
Results
The median age of the patients was 50 years (IQR, 42-50 years), and 305 (100%) were women. Of 202 immune signatures tested, 166 (82.2%) were significantly correlated with TILs. In both trials combined, TILs were significantly associated with pCR (odds ratio, 1.01; 95% CI, 1.01-1.02;
PMC9857319
Conclusions and Relevance
multiple B-cell, early-stage ERBB2/HER2-positive
BREAST CANCER
Results of this study suggest that multiple B-cell–related signatures were more strongly associated with pCR and EFS than TILs, which largely represent T cells. When both TILs and gene expression are available, the prognostic value of immune-related signatures appears to be superior.This prognostic study (in which a co...
PMC9857319
Introduction
early-stage ERBB2/HER2-positive, breast cancer
BREAST CANCER
During the last 2 decades, the outcome of patients with early-stage ERBB2/HER2-positive breast cancer has markedly improved owing to new treatment strategies combining polychemotherapy and multiple ERBB2/HER2-targeted drugs.Increasing evidence suggests that the activation of the host immune system mediates the response...
PMC9857319
Methods
PMC9857319
Neoadjuvant Trials
The CALGB 40601 trial study design, pCR, event-free survival (EFS), overall survival, and genomic correlative studies have been previously published.
PMC9857319
Tumor Gene Expression Analyses and iGESs
Gene expression profiles from pretreatment core biopsies were obtained from 264 of 305 CALGB 40601 trial participants (86.6%) and 142 of 151 PAMELA trial participants (94.0%) (eFigure 1 in the Expression of 202 iGESs from 43 publications (eReferences in the
PMC9857319
TIL Evaluation
In the CALGB 40601 and PAMELA trials, slides from core biopsies were available for 230 of 264 patients (87.1%) and 138 of 142 patients (97.2%) from the RNA-Seq cohort (eFigure 1 in the
PMC9857319
Statistical Analysis
death, Tumour, primary malignant neoplasm, breast cancer
RECURRENCE, TUMOUR, EVENT, DISEASE, REGRESSION, PRIMARY MALIGNANT NEOPLASM
The criteria of the Reporting Recommendations for Tumour Marker Prognostic Studies (REMARK) guidelines were followed for this study.For pCR and EFS modeling, the iGES scores were analyzed as continuous variables. Stromal TILs were analyzed as continuous and discrete variables with different prespecified cutoffs (ie, 20...
PMC9857319
Results
PMC9857319
Baseline Patient Characteristics and TIL Distribution
The characteristics of the 305 patients included in the study are summarized in
PMC9857319
Baseline Characteristics of Patients From the Study Population by Clinical Trial
Leukemia, Cancer
GROUP B, LEUKEMIA, CANCER
Abbreviations: CALGB, Cancer and Leukemia Group B 40601 trial; ET, endocrine therapy; HL, trastuzumab plus lapatinib; TH, weekly paclitaxel plus trastuzumab; THL, TH plus lapatinib; TL, weekly paclitaxel plus lapatinib.Statistical differences were assessed with the Wilcoxon rank sum test (for age) and the Pearson χIn t...
PMC9857319
Comparison of Stromal Tumor-Infiltrating Lymphocyte (TIL) Levels by Hormone Receptor Status (A) and Intrinsic Subtype (B) in the Combined Cohort of the Cancer and Leukemia Group B 40601 Trial and the PAMELA Trial
Statistical differences were assessed with the Kruskal-Wallis test. The horizontal line in each box plot indicates the median of the distribution.
PMC9857319
Association Between TILs and iGESs
TILs
INFILTRATION
We found that 166 of 202 iGESs (82.2%) were significantly correlated with TILs in both studies, 179 in the CALGB 40601 trial and 174 in the PAMELA trial (eTable 3 in the To further study the association between TILs and iGESs, we compared the differences in immune cell infiltration, using our CIBERSORT-derived signatur...
PMC9857319
Heatmap Representing the Different Distributions of the CIBERSORT-Derived Gene Expression Signatures by Tumor-Infiltrating Lymphocyte (TIL) and Immunoglobulin G (IgG) Levels
Leukemia, Cancer
GROUP B, LEUKEMIA, CANCER
Cancer and Leukemia Group B 40601 (CALGB 40601) and PAMELA trial samples were classified into 3 different groups by study, depending on the TIL and IgG levels by tertiles (ie, low, medium, and high TILs; and low, medium, and high IgG). Then, a multiclass significance analysis of microarrays was performed. The standardi...
PMC9857319
Association of TILs and iGESs With pCR in the CALGB 40601 and PAMELA Trials
TILs
In the combined cohort, the percentage of TILs as a continuous variable was significantly associated with pCR, with an odds ratio of 1.01 (95% CI, 1.01-1.02;
PMC9857319
Rates of Pathologic Complete Response (pCR) According to Levels of Tumor-Infiltrating Lymphocytes (TILs) (A) and Immunoglobulin G (IgG) Gene Expression Signature (B)
Both variables were divided by tertiles to illustrate their association with pCR. HL indicates trastuzumab plus lapatinib; TH, weekly paclitaxel plus trastuzumab; THL, TH plus lapatinib; and TL, weekly paclitaxel plus lapatinib.Thirty-six of 202 iGESs (17.8%) were also significantly associated with pCR independently of...
PMC9857319
Association of TILs and iGESs With EFS in the CALGB 40601 Trial
REGRESSION
In the CALGB 40601 trial, 37 iGESs, but not TILs, were significantly associated with EFS in Cox regression models adjusted by treatment group (eTable 6 in the Finally, we wanted to test whether the combination of iGESs and TILs was more prognostic than each alone by comparing multiple multivariable Cox regression model...
PMC9857319
Association of TILs and Immune-Related Gene Expression Signatures With EFS in the Cancer and Leukemia Group B 40601 Trial
tumor
REGRESSION, RESIDUAL DISEASE, TUMOR, INFILTRATING
Abbreviations: AIC, Akaike information criterion; EFS, event-free survival; HR, hormone receptor; LRT, likelihood ratio test; neg, negative; pCR, pathologic complete response; pCRB, in-breast pCR; pos, positive; RD, residual disease; TH, weekly paclitaxel plus trastuzumab; THL, TH plus lapatinib; TIL, tumor infiltratin...
PMC9857319
Discussion
INFILTRATION, BREAST CANCER
In the CALGB 40601 and PAMELA trials, both the proportion of TILs and the multiple iGESs were significantly associated with pCR. Moreover, in the CALGB 40601 trial, several immune signatures were also associated with EFS in univariable and multivariable Cox analyses that included clinical factors and intrinsic subtype,...
PMC9857319
Limitations
SECONDARY, BREAST CANCER
Our study has limitations. First, a substantial proportion of patients included in the CALGB 40601 and PAMELA trials received trastuzumab combined with lapatinib, a dual treatment used in the metastatic setting but not approved for early-stage ERBB2/HER2-positive breast cancer. Moreover, the PAMELA trial differed from ...
PMC9857319
Conclusions
early-stage ERBB2/HER2-positive, breast cancer
BREAST CANCER
To conclude, accumulating evidence supports the validity of using evidence of immune activation, which can be measured with TILs or immune-related gene expression biomarkers, to stratify patients with early-stage ERBB2/HER2-positive breast cancer into different prognostic groups. This study supports that measurement of...
PMC9857319
Subject terms
SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients w...
PMC10684757
Introduction
deaths, infections, ARDS
COVID-19 (CORONAVIRUS DISEASE 2019), VIRUS, ARDS, INFECTIONS
The Coronavirus Disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has inflicted a significant health burden. As of September 2023, there were more than 770 million confirmed infections with 6.9 million deaths worldwidePulmonary surfactant, synthesized and secreted by alveolar type II cells (AT-II), consis...
PMC10684757
Methods
PMC10684757
Study design
acute respiratory failure
VIRAL PNEUMONIA, ACUTE RESPIRATORY FAILURE
This is a pilot, exploratory, dose-adaptive, prospective, randomized, phase-2, open-label, proof-of-concept trial to assess the feasibility, safety, and efficacy of nebulized surfactant (Alveofact®, bovactant) in adult COVID-19 patients requiring mechanical ventilation (NCT04362059, date of registration 24/04/2020). Th...
PMC10684757
Trial procedures
Participants were randomly assigned to receive open-label nebulized surfactant or no intervention in a 3:2 ratio using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV). As patients were unable to consent, consent was obtained from a personal legal representative (PerLR) or p...
PMC10684757
Surfactant composition
The recruiting centre did randomisation with a unique subject identifier specific to that centre. The nebulized surfactant is a natural lyophilized bovine surfactant (Alveofact®) preparation with an approximate composition of phospholipids [phosphatidylcholine (75%), phosphatidylglycerol (13%), phosphatidylethanolamine...
PMC10684757
Nebulizer device
This nebulizer device (Aerogen, Galway, Ireland) has a novel two-layer photo defined aperture plate (PDAP) vibrating mesh generating tiny surfactant droplets with mass median aerodynamic diameter < 3 µm to enhance distal lung depositionThe nebulizer device and the ventilator circuit connections with the controller and ...
PMC10684757
Nebulization dosing and timing
For the first 10-patient cohort, surfactant was administered at 0, 8, and 24-h post-randomization (Fig. Surfactant dosing regimen.
PMC10684757
Exclusion criteria
liver failure, death, allergy, pneumothorax
PULMONARY HAEMORRHAGE, STAGE 4 CHRONIC KIDNEY DISEASE, PNEUMOTHORAX, LIVER FAILURE, ALLERGY
The exclusion criteria were imminent expected death within 24 h, specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary haemorrhage), known or suspected pregnancy, stage 4 chronic kidney disease or requiring dialysis (i.e., estimated glomerular filtration rate < 30 ml/min),...
PMC10684757
Trial outcomes
The co-primary outcome was an improvement in oxygenation (PaO
PMC10684757
Surfactant phosphatidylcholine assessment
RECRUITMENT
Endotracheal aspirates through a closed in-line tracheal suction system were taken from all patients before surfactant nebulization and at 8, 16, 24, 48 and 72 h after recruitment. Samples were filtered and centrifuged at 400 g for 10 min at 4 °C. The supernatant was then lipid extracted by a modified Bligh and Dyer me...
PMC10684757
Adverse event reporting
critically ill, pneumothorax, respiratory and cardiovascular deteriorations, FiOSustained deterioration, respiratory deteriorations, bronchospasm
CRITICALLY ILL, PULMONARY HAEMORRHAGE, PNEUMOTHORAX, LOBAR COLLAPSE, ADVERSE EVENTS, EVENT, EVENTS, BRONCHOSPASM, MULTI-ORGAN FAILURE
COVID-19 participants enrolled in this study were already critically ill with multiple COVID-19 related medical issues and were at risk of ongoing clinical deterioration and multi-organ failure. It was expected that many of these patients would experience events during their clinical pathway, but these were not reporte...
PMC10684757
Statistical analysis
This is a pilot, exploratory dose-adoptive study and power calculations were based on significant dose response under varying assumed true dose response when using matched controls. Baseline data are presented as means (standard deviation) or medians (interquartile range) depending on the Normality of distribution. Cat...
PMC10684757
Feasibility outcomes
failure of breath synchronisation
All patients received all prescribed doses of surfactant. There were two episodes of delays in surfactant delivery due to issues relating to the device, one related to failure of breath synchronisation and one to breath-sensor failure. The devices were replaced immediately on both occasions and patients subsequently re...
PMC10684757
Efficacy outcomes
PMC10684757