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Critical Care Science 2024Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress... (Randomized Controlled Trial)
Randomized Controlled Trial
Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.
BACKGROUND
Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear.
OBJECTIVE
To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia.
METHODS
The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance.
OUTCOMES
The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide.
CONCLUSION
STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.
Topics: Humans; Respiratory Distress Syndrome; Community-Acquired Infections; Prospective Studies; Positive-Pressure Respiration; Pneumonia; Brazil; Colombia; Intensive Care Units; Tidal Volume
PubMed: 38775567
DOI: 10.62675/2965-2774.20240210-en -
European Heart Journal. Digital Health May 2024Atrial fibrillation (AF) is prevalent, undiagnosed in approximately one-third of cases, and is associated with severe complications. Guidelines recommend screening...
AIMS
Atrial fibrillation (AF) is prevalent, undiagnosed in approximately one-third of cases, and is associated with severe complications. Guidelines recommend screening individuals at increased risk of stroke. This report evaluated the digital recruitment procedure and compliance with the follow-up recommendations in participants with screen-detected AF in the Norwegian Atrial Fibrillation self-screening pilot study.
METHODS AND RESULTS
Norwegians ≥65 years were invited through Facebooks posts, web pages, and newspapers to participate in the study. Targeted Facebook posts promoted over 11 days reached 84 208 users and 10 582 visitors to the study homepage. This accounted for 51% of the total homepage visitors ( = 20 704). A total of 2118 (10%) of the homepage visitors provided digital consent to participate after they met the inclusion criteria. The mean (standard deviation) age of the participants was 70 (4) years, and the majority [ = 1569 (74%)] were women. A total of 1849 (87%) participants completed the electrocardiogram self-screening test, identifying AF in 41 (2.2%) individuals. Of these, 39 (95%) participants consulted a general practitioner, and 34 (83%) participants initiated anticoagulation therapy.
CONCLUSION
Digital recruitment and inclusion in digital AF screening with a high rate of initiation of anticoagulation therapy in AF positive screening cases are feasible. However, digital recruitment and inclusion may introduce selection bias with regard to age and gender. Larger studies are needed to determine the efficacy and cost-effectiveness of a fully digital AF screening.
TRIAL REGISTRATION
Clinical trials: NCT04700865.
PubMed: 38774377
DOI: 10.1093/ehjdh/ztae026 -
BMC Pulmonary Medicine May 2024Assessing mechanical properties of the respiratory system (C) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an...
BACKGROUND
Assessing mechanical properties of the respiratory system (C) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals.
METHODS
A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (V) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RC).
RESULTS
During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of C and airway resistance (R) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of C and an overestimation of R were observed in the severe obstruction model.
CONCLUSION
Using the modified dynamic signal analysis approach, respiratory system properties (C and R) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.
Topics: Humans; Airway Resistance; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Respiratory Distress Syndrome; Tidal Volume; Respiratory Mechanics; Lung; Lung Compliance; Models, Biological; Adult
PubMed: 38769572
DOI: 10.1186/s12890-024-03061-2 -
PloS One 2024Hyperinflation is a common procedure to clear secretion, increase lung compliance and enhance oxygenation in mechanically ventilated patients. Hyperinflation can be...
INTRODUCTION
Hyperinflation is a common procedure to clear secretion, increase lung compliance and enhance oxygenation in mechanically ventilated patients. Hyperinflation can be provided as manual hyperinflation (MHI) or ventilator hyperinflation (VHI), where outcomes depend upon the methods of application. Hence it is crucial to assess the application of techniques employed in Sri Lanka due to observed variations from recommended practices.
OBJECTIVE
This study is aimed to evaluate the application and parameters used for MHI and VHI by physiotherapists in intensive care units (ICUs) in Sri Lanka.
METHODOLOGY
An online survey was conducted among physiotherapists who are working in ICUs in Sri Lanka using WhatsApp groups and other social media platforms.
RESULTS
A total of 96 physiotherapists responded. The survey comprised of three sections to obtain information about socio-demographic data, MHI practices and VHI practices. Most of the respondents (47%) worked in general hospitals and 74% of participants had a bachelor's degree in physiotherapy; 31.3% had 3-6 years of experience; 93.8% used hyperinflation, and 78.9% used MHI. MHI was performed routinely and as needed to treat low oxygen levels, abnormal breath sounds, and per physician orders while avoiding contraindications. Self-inflation bags are frequently used for MHI (40.6%). Only a few participants (26%) used a manometer or tracked PIP. In addition to the supine position, some participants (37.5%) used the side-lying position. Most physiotherapists followed the recommended MHI technique: slow squeeze (57.3%), inspiratory pause (45.8%), and quick release (70.8%). VHI was practised by 19.8%, with medical approval and it was frequently performed by medical staff compared to physiotherapists. Treatment time, number of breaths, and patient positioning varied, and parameters were not well-defined.
CONCLUSION
The study found that MHI was not applied with the recommended PIP, and VHI parameters were not identified. The study indicates a need to educate physiotherapists about current VHI and MHI practice guidelines.
Topics: Humans; Sri Lanka; Physical Therapists; Surveys and Questionnaires; Respiration, Artificial; Male; Female; Adult; Intensive Care Units; Critical Care; Ventilators, Mechanical
PubMed: 38768181
DOI: 10.1371/journal.pone.0297880 -
Trials May 2024The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior...
SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory...
BACKGROUND
The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.
METHODS
We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SO:FO ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.
DISCUSSION
Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.
TRIAL REGISTRATION
The trial was registered at www.
CLINICALTRIALS
gov on 5/31/2023 (NCT05881135).
TRIAL STATUS
Currently enrolling.
Topics: Humans; Cytidine Diphosphate Choline; Double-Blind Method; SARS-CoV-2; COVID-19; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment; Clinical Trials, Phase II as Topic; Pneumonia, Viral; Treatment Outcome; Hypoxia; Male; Pandemics; Coronavirus Infections; Hospitalization; Female; Betacoronavirus; Clinical Trials, Phase I as Topic; Respiratory Insufficiency; Administration, Intravenous; Adult
PubMed: 38760804
DOI: 10.1186/s13063-024-08155-0 -
Emergency Medicine Journal : EMJ May 2024Lidocaine patches, applied over rib fractures, may reduce pulmonary complications in older patients. Known barriers to recruiting older patients in emergency settings...
BACKGROUND
Lidocaine patches, applied over rib fractures, may reduce pulmonary complications in older patients. Known barriers to recruiting older patients in emergency settings necessitate a feasibility trial. We aimed to establish whether a definitive randomised controlled trial (RCT) evaluating lidocaine patches in older patients with rib fracture(s) was feasible.
METHODS
This was a multicentre, parallel-group, open-label, feasibility RCT in seven hospitals in England and Scotland. Patients aged ≥65 years, presenting to ED with traumatic rib fracture(s) requiring hospital admission were randomised to receive up to 3×700 mg lidocaine patches (Ralvo), first applied in ED and then once daily for 72 hours in addition to standard care, or standard care alone. Feasibility outcomes were recruitment, retention and adherence. Clinical end points (pulmonary complications, pain and frailty-specific outcomes) and patient questionnaires were collected to determine feasibility of data collection and inform health economic scoping. Interviews and focus groups with trial participants and clinicians/research staff explored the understanding and acceptability of trial processes.
RESULTS
Between October 23, 2021 and October 7, 2022, 206 patients were eligible, of whom 100 (median age 83 years; IQR 74-88) were randomised; 48 to lidocaine patches and 52 to standard care. Pulmonary complications at 30 days were determined in 86% of participants and 83% of expected 30-day questionnaires were returned. Pulmonary complications occurred in 48% of the lidocaine group and 59% in standard care. Pain and some frailty-specific outcomes were not feasible to collect. Staff reported challenges in patient compliance, unfamiliarity with research measures and overwhelming the patients with research procedures.
CONCLUSION
Recruitment of older patients with rib fracture(s) in an emergency setting for the evaluation of lidocaine patches is feasible. Refinement of data collection, with a focus on the collection of pain, frailty-specific outcomes and intervention delivery are needed before progression to a definitive trial.
TRIAL REGISTRATION NUMBER
ISRCTN14813929.
PubMed: 38760021
DOI: 10.1136/emermed-2024-213905 -
Perioperative Medicine (London, England) May 2024This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.
OBJECTIVE
This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.
METHODS
Obese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 μg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO) and arterial partial pressure of carbon dioxide (PaCO). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6.
RESULTS
The time of surgery, anesthesia, CO pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6.
CONCLUSION
In obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.
PubMed: 38755633
DOI: 10.1186/s13741-024-00396-6 -
PloS One 2024During the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include...
INTRODUCTION
During the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include precise gas delivery, rapid adjustments, durability, and user-friendliness, often achieved through solenoid valves. However, few solenoid-valve assisted low-cost ventilator (LCV) designs have been published, and gas exchange evaluation during LCV testing is lacking. This study describes the development and performance evaluation of a solenoid-valve assisted low-cost ventilator (SV-LCV) in vitro and in vivo, focusing on gas exchange and respiratory mechanics.
METHODS
The SV-LCV, a fully open ventilator device, was developed with comprehensive hardware and design documentation, utilizing solenoid valves for gas delivery regulation. Lung simulator testing calibrated tidal volumes at specified inspiratory and expiratory times, followed by in vivo testing in a porcine model to compare SV-LCV performance with a conventional ventilator.
RESULTS
The SV-LCV closely matched the control ventilator's respiratory profile and gas exchange across all test cycles. Lung simulator testing revealed direct effects of compliance and resistance changes on peak pressures and tidal volumes, with no significant changes in respiratory rate. In vivo testing demonstrated comparable gas exchange parameters between SV-LCV and conventional ventilator across all cycles. Specifically, in cycle 1, the SV-LCV showed arterial blood gas (ABG) results of pH 7.54, PCO2 34.5 mmHg, and PO2 91.7 mmHg, compared to the control ventilator's ABG of pH 7.53, PCO2 37.1 mmHg, and PO2 134 mmHg. Cycle 2 exhibited ABG results of pH 7.53, PCO2 33.6 mmHg, and PO2 84.3 mmHg for SV-LCV, and pH 7.5, PCO2 34.2 mmHg, and PO2 93.5 mmHg for the control ventilator. Similarly, cycle 3 showed ABG results of pH 7.53, PCO2 32.1 mmHg, and PO2 127 mmHg for SV-LCV, and pH 7.5, PCO2 35.5 mmHg, and PO2 91.3 mmHg for the control ventilator.
CONCLUSION
The SV-LCV provides similar gas exchange and respiratory mechanic profiles compared to a conventional ventilator. With a streamlined design and performance akin to commercially available ventilators, the SV-LCV presents a viable, readily available, and reliable short-term solution for overcoming ventilator supply shortages during crises.
Topics: Animals; Swine; Ventilators, Mechanical; COVID-19; Respiratory Mechanics; Pulmonary Gas Exchange; Equipment Design; Respiration, Artificial; SARS-CoV-2; Tidal Volume
PubMed: 38753734
DOI: 10.1371/journal.pone.0303443 -
BJUI Compass May 2024To analyse the latest evidence on the relative harms and benefits of screening and diagnostic pathways with close examination of (i) men aged 50 years or older, (ii)... (Review)
Review
OBJECTIVE
To analyse the latest evidence on the relative harms and benefits of screening and diagnostic pathways with close examination of (i) men aged 50 years or older, (ii) men whose ethnicity places them at higher risk and (iii) men with a family history.
METHODS
We conducted a literature search using PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases and other sources, from January 1990 to 25 January 2023. Two independent reviewers selected for randomised controlled trials (RCTs) and cohort studies which met our inclusion criteria.
RESULTS
Twenty-eight articles were selected, from six trials, including the Göteborg trial-reported separately from European Randomised Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA)-based screening led to the increased detection of low-grade cancer and reduction of advanced/metastatic disease but had contradictory effects on prostate cancer (PCa)-specific mortality (no difference or reduced), possibly due to issues of contamination or compliance. Screening men from a relatively young age (50-55) reduced risk of PCa-specific mortality in a subanalysis of an 18-year follow-up study and in a 17-year cohort study from the main Göteborg trial. Moreover, one Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial analysis reported a trend of reduced risk of PCa-specific mortality for men with a family history who were screened. [Correction added on 05 March 2024, after first online publication: "Cancer Screening Trial" has been added to the preceding sentence.] However, we did not find relevant studies for ethnicity.
CONCLUSION
Under current UK practice, the choice to conduct a PSA test relies on a shared decision-making approach guided by known risk factors. However, we found there was a lack of strong evidence on the harms and benefits of PSA screening by socio-clinical risk factors and suggest further research is required to understand the long-term impact of screening on high-risk populations in the current diagnostic setting.
PubMed: 38751945
DOI: 10.1002/bco2.326 -
ESMO Open May 2024This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer...
BACKGROUND
This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), non-MTC thyroid cancer (TC), and tumor agnostic (TA) patients (Data cut-off: January 2023) from the LIBRETTO-001 trial.
PATIENTS AND METHODS
Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). Patients with MTC also completed a modified version of the Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The proportion of patients with improved, stable, or worsened status after baseline was reported. PROs were summarized at 3 years (cycle 37) post-baseline for the NSCLC and MTC cohorts, and at 2 years (cycle 25) post-baseline for the TC and TA cohorts. Time-to-event outcomes (time to first improvement or worsening and duration of improvement) were reported.
RESULTS
The baseline assessment was completed by 200 (63.3%), 209 (70.8%), 50 (76.9%), and 38 (73.1%) patients in the NSCLC, MTC, TC, and TA cohorts, respectively. The total compliance rate was 80%, 82%, 70%, and 85%, respectively. Approximately 75% (NSCLC), 81% (MTC), 75% (TC), and 40% (TA) of patients across all cohorts reported improved or stable QLQ-C30 scores at year 3 (NSCLC and MTC) or year 2 (TC and TA) with continuous selpercatinib use. Across cohorts, the median time to first improvement ranged from 2.0 to 19.4 months, the median duration of improvement ranged from 1.9 to 28.2 months, and the median time to first worsening ranged from 5.6 to 44.2 months. The total compliance rate for the mSTIDAT was 83.7% and the proportion of patients with MTC who reported diarrhea on the mSTIDAT was reduced from 80.8% at baseline to 35.6% at year 3.
CONCLUSIONS
A majority of patients with RET-driven cancers improved or remained stable on most QLQ-C30 domains, demonstrating favorable health-related quality of life as measured by the QLQ-C30 during long-term treatment with selpercatinib.
Topics: Humans; Patient Reported Outcome Measures; Male; Female; Middle Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Thyroid Neoplasms; Pyrazoles; Aged; Quality of Life; Proto-Oncogene Proteins c-ret; Carcinoma, Neuroendocrine; Pyridines; Adult
PubMed: 38749381
DOI: 10.1016/j.esmoop.2024.103444