A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel: A Randomized Clinical Trial.

Importance: Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections. Objective: To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP. Design, Setting, and Participants: A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups. Interventions: Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness. Main Outcomes and Measures: The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed. Results: Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group. Conclusions and Relevance: Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza. Trial Registration: ClinicalTrials.gov Identifier: NCT01249625.

GRAvity- versus Wall suction-drIven large volume Thoracentesis: a rAndomized controlled Study (GRAWITAS study).

BACKGROUND: Prior studies found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION: Does wall suction drainage result in more chest discomfort compared to gravity drainage in patients undergoing large volume thoracentesis? STUDY DESIGN AND METHODS: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥500 mL were assigned to wall suction or gravity drainage in a 1:1 ratio. Wall suction was performed with suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 minutes. Secondary outcomes included measures of post procedure chest discomfort, breathlessness, procedure time, volume of fluid drained and complication rates. RESULTS: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (p = 0.08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 minutes. No differences in rate of pneumothorax or re-expansion pulmonary edema were noted between the two groups. INTERPRETATION: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement.

Bronchoalveolar Lavage (BAL) and Pathologic Assessment of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): The EVALI-BAL Study, A Multicenter Cohort.

BACKGROUND: E-cigarette or vaping-use related acute lung injury (EVALI) is a spectrum of radiographic and histologic patterns consistent with acute to subacute lung injury. However, limited data exist characterizing bronchoalveolar lavage (BAL) findings. The goal of this study is to further define the pathologic findings from BAL and biopsy samples of subjects with EVALI across 7 institutions. METHODS: A multicentered registry of patients admitted with EVALI who underwent flexible bronchoscopy with BAL+/-transbronchial biopsy from July 2019 to April 2021 was compiled for retrospective evaluation from 7 academic institutions throughout the United States. Radiographic and cytopathologic findings and frequencies were correlated with the substance vaped. RESULTS: Data from 21 subjects (42.9% women) who were predominantly White (76.2%) with a median age of 25 years (range, 16 to 68) with EVALI were included in this study. Sixteen patients (76.2%) reported use of tetrahydrocannabinol; the remainder used nicotine. BAL was performed in 19 of the 21 subjects, and transbronchial lung biopsy was performed in 7 subjects. BAL findings revealed neutrophilic predominance (median, 59.5%, range, 3.1 to 98) in most cases. Ten BAL samples demonstrated pulmonary eosinophilia ranging from 0.2% to 49.1% with one subject suggesting a diagnosis of acute eosinophilic pneumonia associated with the use of e-cigarettes. Lipid-laden macrophages were noted in 10 of 15 reports (66.7%). Transbronchial biopsy most frequently demonstrated patterns of organizing pneumonia (57.1%). CONCLUSION: EVALI-associated BAL findings typically demonstrate a spectrum of nonspecific inflammatory changes, including neutrophilia, lipid-laden macrophages, and in some cases eosinophilia.

Take-home kits to detect respiratory viruses among healthcare personnel: Lessons learned from a cluster randomized clinical trial.

BACKGROUND: Health care personnel (HCP) working in outpatient settings routinely interact with patients with acute respiratory illnesses. Absenteeism following symptom development and lack of staff trained to obtain samples limit efforts to identify pathogens among infected HCP. METHODS: The Respiratory Protection Effectiveness Clinical Trial assessed respiratory infection incidence among HCP between 2011 and 2015. Research assistants obtained anterior nasal and oropharyngeal swabs from HCP in the workplace following development of respiratory illness symptoms and randomly while asymptomatic. Participants received take-home kits to self-collect swabs when absent from work. Samples mailed to a central laboratory were tested for respiratory viruses by reverse transcription polymerase chain reaction. RESULTS: Among 2,862 participants, 3,467 swabs were obtained from symptomatic participants. Among symptomatic HCP, respiratory virus was detected in 904 of 3,467 (26.1%) samples. Self-collected samples by symptomatic HCP at home had higher rates of viral detection (40.3%) compared to 24% obtained by trained research assistants in the workplace (P < .001). CONCLUSIONS: In this randomized clinical trial, take-home kits were an easily implemented, effective method to self-collect samples by HCP. Other studies have previously shown relative equivalence of self-collected samples to those obtained by trained healthcare workers. Take-home kit self-collection could diminish workforce exposures and decrease the demand for personnel protective equipment worn to protect workers who collect respiratory samples.

Cortical auditory dysfunction in benign rolandic epilepsy.

PURPOSE: To evaluate cortical auditory function, including speech recognition, in children with benign rolandic epilepsy (BRE). METHODS: Fourteen children, seven patients with BRE and seven matched controls, underwent audiometric and behavioral testing, simultaneous EEG recordings, and auditory-evoked potential recordings with speech and tones. Speech recognition was tested under multiple listening conditions. RESULTS: All participants demonstrated normal speech recognition abilities in quiet, as well as normal peripheral and subcortical auditory function. BRE patients performed significantly worse than controls when speech recognition was tested under adverse listening conditions, including background noise. Five BRE patients who were impaired on two or more tests had centrotemporal spiking on awake EEG. There were no significant group differences in the latency or amplitude of early N100 cortical responses to speech or tones. Conversely, the mismatch negativity, a preattentive index of cortical processing that is elicited passively, was absent or prolonged for speech, but not tones, in BRE patients as compared to controls. DISCUSSION: Children with BRE demonstrated specific speech recognition impairments. Our evoked potential findings indicate that these behavioral impairments reflect dysfunction of nonprimary auditory cortex and cannot be attributed solely to attention difficulties. A possible association between auditory impairments and centrotemporal spiking (>1/min) on awake EEG was identified. The pattern of speech recognition impairments observed is a known risk factor for academic difficulties in school-age children. Our results underscore the importance of comprehensive auditory testing, using behavioral and electrophysiological measures, in children with BRE.

Protecting Healthcare Personnel in Outpatient Settings: The Influence of Mandatory Versus Nonmandatory Influenza Vaccination Policies on Workplace Absenteeism During Multiple Respiratory Virus Seasons.

OBJECTIVE To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP). DESIGN Retrospective observational cohort study. SETTING This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies. PARTICIPANTS The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites. METHODS To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012-2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models. RESULTS The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07-0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012-2013 and 2013-2014, 0.82; 95% CI, 0.72-0.93; OR for 2014-2015, 0.81; 95% CI, 0.69-0.95). CONCLUSIONS These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies. Infect Control Hosp Epidemiol 2018;39:452-461.

Study Design and Rationale: A Multicenter, Prospective Trial of Electromagnetic Bronchoscopic and Electromagnetic Transthoracic Navigational Approaches for the Biopsy of Peripheral Pulmonary Nodules (ALL IN ONE Trial).

BACKGROUND: Pulmonary nodules are a common but difficult issue for physicians as most identified on imaging are benign but those identified early that are cancerous are potentially curable. Multiple diagnostic options are available, ranging from radiographic surveillance, minimally invasive biopsy (bronchoscopy or transthoracic biopsy) to more invasive surgical biopsy/resection. Each technique has differences in diagnostic yield and complication rates with no established gold standard. Currently, the safest approach is bronchoscopic but it is limited by variable diagnostic yields. Percutaneous approaches are limited by nodule location and complications. With the recent advent of electromagnetic navigation (EMN), a combined bronchoscopic and transthoracic approach is now feasible in a single, staged procedure. Here, we present the study design and rationale for a single-arm trial evaluating a staged approach for the diagnosis of pulmonary nodules. METHODS: Participants with 1-3 cm, intermediate to high-risk pulmonary nodules will undergo a staged approach with endobronchial ultrasound (EBUS) followed by EMN-bronchoscopy (ENB), then EMN-transthoracic biopsy (EMN-TTNA) with the procedure terminated at any stage after a diagnosis is made via rapid onsite cytopathology. We aim to recruit 150 EMN participants from eight academic and community settings to show significant improvements over other historic bronchoscopic guided techniques. The primary outcome is overall diagnostic yield of the staged approach. CONCLUSION: This is the first study designed to evaluate the diagnostic yield of a staged procedure using EBUS, ENB and EMN-TTNA for the diagnosis of pulmonary nodules. If effective, the staged procedure will increase minimally invasive procedural diagnostic yield for pulmonary nodules.

A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

Benign rolandic epilepsy (BRE) and Landau-Kleffner syndrome (LKS) are similar epilepsy syndromes with sleep-accentuated epileptiform activity, sporadic seizures, and language dysfunction. Levetiracetam has been associated with improved language function in LKS and seizure reduction in BRE. We hypothesized levetiracetam would improve language function in children with BRE. A pilot study was performed with six children (aged 6-12) with BRE and evidence of impaired auditory comprehension and verbal memory. Children were transitioned from their current anticonvulsant to 40 mg/kg/day levetiracetam over a 2-week period and retested at 6 months. At 6 months, three of four children with baseline auditory comprehension impairments performed normally (P=0.06), and five had improved auditory verbal memory (P=0.08). Seizures improved in five, decreasing from 2.7 to 1.0 seizure per 6 months (P=0.11). Results from this pilot study suggest that levetiracetam may have a beneficial effect on language in children with BRE.