Previous trials of higher positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) failed to demonstrate mortality benefit, possibly because of differences in lung ...recruitability among patients with ARDS.
To determine whether the physiological response to increased PEEP is associated with mortality.
In a secondary analysis of the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship between the initial response to changes in PEEP after randomization and mortality. We sought to corroborate our findings using data from a different trial of higher PEEP (ExPress, n = 749).
The oxygenation response (change in ratio of arterial partial pressure of oxygen to fraction of inspired oxygen: P/F) after the initial change in PEEP after randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47) and was only weakly related to baseline P/F or the magnitude of PEEP change. Among patients in whom PEEP was increased after randomization, an increase in P/F was associated with reduced mortality (multivariable logistic regression; adjusted odds ratio, 0.80 95% confidence interval, 0.72-0.89 per 25-mm Hg increase in P/F), particularly in patients with severe disease (baseline P/F less-than-or-equal-to 150 mm Hg). Changes in compliance and dead space were not associated with mortality. These findings were confirmed by a similar analysis of data from the ExPress trial.
Patients with ARDS who respond to increased PEEP by improved oxygenation have a lower risk of death. The oxygenation response to PEEP might be used to predict whether patients will benefit from higher versus lower PEEP.
Sud et al. discuss the comparative effectiveness of protective ventilation strategies for moderate and severe acute respiratory distress syndrome. The authors performed a network meta-analysis of ...randomized trials. They analyzed 34 trials including 9,085 adults with primarily moderate-to-severe ARDS (median baseline PaO2/FiO2, 118; interquartile range, 110-143). Their findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for critically ill adults with moderate-to-severe ARDS.
CONTEXT Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and ...plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown. OBJECTIVE To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit. DATA SOURCES Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit. STUDY SELECTION Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria. DATA EXTRACTION Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping. DATA SYNTHESIS Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range IQR, 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73). CONCLUSIONS RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.
Quantum algorithms offer a dramatic speedup for computational problems in material science and chemistry. However, any near-term realizations of these algorithms will need to be optimized to fit ...within the finite resources offered by existing noisy hardware. Here, taking advantage of the adjustable coupling of gmon qubits, we demonstrate a continuous two-qubit gate set that can provide a threefold reduction in circuit depth as compared to a standard decomposition. We implement two gate families: an imaginary swap-like (iSWAP-like) gate to attain an arbitrary swap angle, θ, and a controlled-phase gate that generates an arbitrary conditional phase, ϕ. Using one of each of these gates, we can perform an arbitrary two-qubit gate within the excitation-preserving subspace allowing for a complete implementation of the so-called Fermionic simulation (fSim) gate set. We benchmark the fidelity of the iSWAP-like and controlled-phase gate families as well as 525 other fSim gates spread evenly across the entire fSim (θ, ϕ) parameter space, achieving a purity-limited average two-qubit Pauli error of 3.8 × 10−3 per fSim gate.
Superconducting qubits are an attractive platform for quantum computing since they have demonstrated high-fidelity quantum gates and extensibility to modest system sizes. Nonetheless, an outstanding ...challenge is stabilizing their energy-relaxation times, which can fluctuate unpredictably in frequency and time. Here, we use qubits as spectral and temporal probes of individual two-level-system defects to provide direct evidence that they are responsible for the largest fluctuations. This research lays the foundation for stabilizing qubit performance through calibration, design, and fabrication.
Mitral valve repair (MVr) is now the treatment of choice to correct severe degenerative mitral regurgitation (MR). Repair rates vary greatly from centre to centre, and the concept of heart valve ...centres of excellence has been established.
The purpose of this study was to see whether large international centre repair rates, and outcomes, are transferrable to medium-sized centres with an interest in mitral repair.
Between 2011 and 2018, a total of 346 patients underwent mitral valve surgery by a single surgeon. Of these, 238 consecutive patients had repairs, or attempted repairs for degenerative MR, and are included in this study.
The study sample consisted of 71% male patients and had a mean age of 64.4 ± 12.3 years; 66% of the study population had concomitant procedures. The overall repair rate in this cohort is 99%. Mean follow up was 3.7 ± 1.9 years. At 5 years, the freedom from MR ≥ 3+ was 95.9 ± 1.9% and at 7 years 91.1 ± 3.8%. Freedom from reoperation at 5 years was 92.9 ± 3.7%, while the 5 years actuarial survival was 89.1 ± 3.7%. On a multivariate analysis, predischarge echo grade was associated with higher risk of future reoperation (odds ratio (OR) = 21.82,
= 0.05). Only age (OR = 1.3,
= 0.03) was predictive of long-term survival.
In specialised medium-sized heart centres, where the surgical team have undergone specialist mitral training, favourable short- and long-term outcomes are achievable with mitral repair rates similar to those from large international centres of excellence. In these heart centres, early surgery should be considered for all patients with severe degenerative MR.
Background
Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe.
Objective
To determine effects of ...prone versus supine ventilation in AHRF and severe hypoxemia partial pressure of arterial oxygen (PaO
2
)/inspired fraction of oxygen (FiO
2
) <100 mmHg compared with moderate hypoxemia (100 mmHg ≤ PaO
2
/FiO
2
≤ 300 mmHg).
Design
Systematic review and meta-analysis.
Data Sources
Electronic databases (to November 2009) and conference proceedings.
Methods
Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO
2
/FiO
2
<100 mmHg. Meta-analyses used study-level random-effects models.
Results
Ten trials (
N
= 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO
2
/FiO
2
<100 mmHg risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74–0.96;
p
= 0.01; seven trials,
N
= 555 but not in patients with PaO
2
/FiO
2
≥100 mmHg (RR 1.07, 95% CI 0.93–1.22;
p
= 0.36; seven trials,
N
= 1,169). Risk ratios differed significantly between subgroups (interaction
p
= 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO
2
/FiO
2
thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27–39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16–1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24–2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02–9.69). There was no statistical between-trial heterogeneity for most clinical outcomes.
Conclusions
Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.
In this trial of intravenous vitamin C in adult patients with sepsis, those who received a vitamin C infusion had a higher risk of death or persistent organ dysfunction at 28 days than those who ...received placebo.
Objective To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared ...with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS.Design Systematic review and meta-analysis.Data sources Medline, CINAHL, Embase, and CENTRAL (to October 2006), proceedings from four conferences, and additional information from authors of 10 trials.Review methods Two reviewers independently selected parallel group randomised controlled trials comparing nitric oxide with control and extracted data related to study methods, clinical and physiological outcomes, and adverse events.Main outcome measures Mortality, duration of ventilation, oxygenation, pulmonary arterial pressure, adverse events. Results 12 trials randomly assigning 1237 patients met inclusion criteria. Overall methodological quality was good. Using random effects models, we found no significant effect of nitric oxide on hospital mortality (risk ratio 1.10, 95% confidence interval 0.94 to 1.30), duration of ventilation, or ventilator-free days. On day one of treatment, nitric oxide increased the ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) (13%, 4% to 23%) and decreased the oxygenation index (14%, 2% to 25%). Some evidence suggested that improvements in oxygenation persisted until day four. There was no effect on mean pulmonary arterial pressure. Patients receiving nitric oxide had an increased risk of developing renal dysfunction (1.50, 1.11 to 2.02).Conclusions Nitric oxide is associated with limited improvement in oxygenation in patients with ALI or ARDS but confers no mortality benefit and may cause harm. We do not recommend its routine use in these severely ill patients.
This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).
A multidisciplinary panel ...conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.
For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H
O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS.
The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.
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