Changes in respiratory symptoms during 48 weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies.
ARD-3150 (吸入环丙沙星脂质体) 治疗支气管扩张症 48 周期间呼吸道症状的变化: ORBIT-3 和-4 研究结果。
- 作者列表："Chalmers JD","Cipolla D","Thompson B","Davis AM","O'Donnell A","Tino G","Gonda I","Haworth C","Froehlich J
INTRODUCTION:It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48-weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment. METHODS:A post-hoc analysis of 2 identical randomised trials of ARD-3150 (ORBIT-3 and -4) administered 28-days on and 28 days off in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The quality of life bronchiectasis respiratory symptom scale (QOL-B-RSS), which has a 1-week recall period, was administered every 28-days. We examined whether respiratory symptoms improved during on-treatment periods and the relationship of changes in QOL-B-RSS to changes in bacterial load using a mixed model repeated measures approach. RESULTS:ARD-3150 treatment resulted in a significant improvement in respiratory symptoms during the on-treatment periods with concordant results between ORBIT-3 (estimate 1.4 points, standard error (se) 0.49, p=0.004) and ORBIT-4 (estimate 1.1 point, SE0.41, p=0.006). The proportion of patients achieving a symptom improvement above the minimum clinically important difference was higher with ARD-3150 compared to placebo during on-treatment cycles (p=0.024). Changes in respiratory symptoms were correlated with changes in bacterial load in the treatment group (r=-0.89, p<0.0001). Individual estimates for decrements in the QOL-B RSS during exacerbation were -9.4 points (se 0.91) in ORBIT-3 and -10.8 points (0.74) in ORBIT-4 (both p<0.0001). CONCLUSION:Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis.
介绍: 不知道吸入抗生素是否能改善支气管扩张患者的呼吸道症状。在最近的 3 期眼眶试验中，使用预先设定的分析方法比较基线症状与 48 周后的症状，ARD-3150 (吸入脂质体环丙沙星) 治疗 48 周并没有显著改善症状,当患者已经停止治疗 28 天。这种分析方法没有考虑到积极治疗时症状的可能改善。 方法: 对 2 项相同的 ARD-3150 随机试验 (ORBIT-3 和-4) 进行事后分析。对支气管扩张和慢性绿脓杆菌感染患者给予 28 天和 28 天的治疗。生活质量支气管扩张呼吸症状量表 (QOL-B-RSS)，有 1 周的回忆期，每 28 天给药一次。我们使用混合模型重复测量方法检测了治疗期间呼吸道症状是否改善，以及 QOL-B-RSS 的变化与细菌负荷变化的关系。 结果: 在治疗期间，ARD-3150 治疗导致呼吸道症状显著改善，ORBIT-3 之间的结果一致 (估计 1.4 分，标准误差 (se) 0.49, p = 0.004) 和 ORBIT-4 (估计 1.1 点，SE0.41，p = 0.006)。在治疗周期中，与安慰剂相比，ARD-3150 患者的症状改善高于最小临床重要差异的比例较高 (p = 0.024)。治疗组呼吸道症状变化与细菌负荷变化相关 (r =-0.89，p<0.0001)。恶化期间 QOL-B RSS 中减少量的个体估计值为-9.4 分 (se 0.91)，轨道-3 和-10.8 分 (0.74) 在轨道-4 (均 p<0.0001)。 结论: 吸入 ARD-3150 可显著改善治疗期间的呼吸道症状，而非治疗期间的症状消失。这些结果支持减少细菌负荷可改善支气管扩张患者呼吸道症状的概念。
METHODS:Background Dye localization is a useful method for the resection of unidentifiable small pulmonary lesions. This study compares the transbronchial route with augmented fluoroscopic bronchoscopy (AFB) and conventional transthoracic CT-guided methods for preoperative dye localization in thoracoscopic surgery. Methods Between April 2015 and March 2019, a total of 231 patients with small pulmonary lesions who received preoperative dye localization via AFB or percutaneous CT-guided technique were enrolled in the study. A propensity-matched analysis, incorporating preoperative variables, was used to compare localization and surgical outcomes between the two groups. Results After matching, a total of 90 patients in the AFB group ( N = 30) and CT-guided group ( N = 60) were selected for analysis. No significant difference was noted in the demographic data between both the groups. Dye localization was successfully performed in 29 patients (96.7%) and 57 patients (95%) with AFB and CT-guided method, respectively. The localization duration (24.1 ± 8.3 vs. 21.4 ± 12.5 min, p = 0.297) and equivalent dose of radiation exposure (3.1 ± 1.5 vs. 2.5 ± 2.0 mSv, p = 0.130) were comparable in both the groups. No major procedure-related complications occurred in either group; however, a higher rate of pneumothorax (0 vs. 16.7%, p = 0.029) and focal intrapulmonary hemorrhage (3.3 vs. 26.7%, p = 0.008) was noted in the CT-guided group. Conclusion AFB dye marking is an effective alternative for the preoperative localization of small pulmonary lesions, with a lower risk of procedure-related complications than the conventional CT-guided method.
METHODS:Background The use of artificial intelligence, including machine learning, is increasing in medicine. Use of machine learning is rising in the prediction of patient outcomes. Machine learning may also be able to enhance and augment anesthesia clinical procedures such as airway management. In this study, we sought to develop a machine learning algorithm that could classify vocal cords and tracheal airway anatomy real-time during video laryngoscopy or bronchoscopy as well as compare the performance of three novel convolutional networks for detecting vocal cords and tracheal rings. Methods Following institutional approval, a clinical dataset of 775 video laryngoscopy and bronchoscopy videos was used. The dataset was divided into two categories for use for training and testing. We used three convolutional neural networks (CNNs): ResNet, Inception and MobileNet. Backpropagation and a mean squared error loss function were used to assess accuracy as well as minimize bias and variance. Following training, we assessed transferability using the generalization error of the CNN, sensitivity and specificity, average confidence error, outliers, overall confidence percentage, and frames per second for live video feeds. After the training was complete, 22 models using 0 to 25,000 steps were generated and compared. Results The overall confidence of classification for the vocal cords and tracheal rings for ResNet, Inception and MobileNet CNNs were as follows: 0.84, 0.78, and 0.64 for vocal cords, respectively, and 0.69, 0.72, 0.54 for tracheal rings, respectively. Transfer learning following additional training resulted in improved accuracy of ResNet and Inception for identifying the vocal cords (with a confidence of 0.96 and 0.93 respectively). The two best performing CNNs, ResNet and Inception, achieved a specificity of 0.985 and 0.971, respectively, and a sensitivity of 0.865 and 0.892, respectively. Inception was able to process the live video feeds at 10 FPS while ResNet processed at 5 FPS. Both were able to pass a feasibility test of identifying vocal cords and tracheal rings in a video feed. Conclusions We report the development and evaluation of a CNN that can identify and classify airway anatomy in real time. This neural network demonstrates high performance. The availability of artificial intelligence may improve airway management and bronchoscopy by helping to identify key anatomy real time. Thus, potentially improving performance and outcomes during these procedures. Further, this technology may theoretically be extended to the settings of airway pathology or airway management in the hands of experienced providers. The researchers in this study are exploring the performance of this neural network in clinical trials.
METHODS:BACKGROUND:The optimal mode of delivering topical anesthesia during flexible bronchoscopy remains unknown. This article compares the efficacy and safety of nebulized lignocaine, lignocaine oropharyngeal spray, or their combination. METHODS:Consecutive subjects were randomized 1:1:1 to receive nebulized lignocaine (2.5 mL of 4% solution, group A), oropharyngeal spray (10 actuations of 10% lignocaine, group B), or nebulization (2.5 mL, 4% lignocaine) and two actuations of 10% lignocaine spray (group C). The primary outcome was the subject-rated severity of cough according to a visual analog scale. The secondary outcomes included bronchoscopist-rated severity of cough and overall procedural satisfaction on a visual analog scale, total lignocaine dose, subject's willingness to undergo a repeat procedure, adverse reactions to lignocaine, and others. RESULTS:A total of 1,050 subjects (median age, 51 years; 64.8% men) were included. The median (interquartile range) score for subject-rated cough severity was significantly lower in group B compared to group C or group A (4 [1-10] vs 11 [4-24] vs 13 [5-30], respectively; P < .001). The bronchoscopist-rated severity of cough was also the least (P < .001), and the overall satisfaction was highest in group B (P < .001). The cumulative lignocaine dose administered was the least in group B (P < .001). A significantly higher proportion of subjects (P < .001) were willing to undergo a repeat bronchoscopy in group B (73.7%) than in groups A (49.1%) and C (59.4%). No lignocaine-related adverse events were observed. CONCLUSIONS:Ten actuations of 10% lignocaine oropharyngeal spray were superior to nebulized lignocaine or their combination for topical anesthesia during diagnostic flexible bronchoscopy. TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT03109392; URL: www.clinicaltrials.gov.