Lung-protective ventilation initiated in the emergency department (LOV-ED): A study protocol for a quasi-experimental, before-after trial aimed at reducing pulmonary complications

INTRODUCTION: In critically ill patients, acute respiratory distress syndrome (ARDS) and ventilator-associated conditions (VACs) are associated with increased mortality, survivor morbidity and healthcare resource utilisation. Studies conclusively demonstrate that initial ventilator settings in patients with ARDS, and at risk for it, impact outcome. No studies have been conducted in the emergency department (ED) to determine if lung-protective ventilation in patients at risk for ARDS can reduce its incidence. Since the ED is the entry point to the intensive care unit for hundreds of thousands of mechanically ventilated patients annually in the USA, this represents a knowledge gap in this arena. A lung-protective ventilation strategy was instituted in our ED in 2014. It aims to address the parameters in need of quality improvement, as demonstrated by our previous research: (1) prevention of volutrauma; (2) appropriate positive end-expiratory pressure setting; (3) prevention of hyperoxia; and (4) aspiration precautions. METHODS AND ANALYSIS: The lung-protective ventilation initiated in the emergency department (LOV-ED) trial is a single-centre, quasi-experimental before-after study testing the hypothesis that lung-protective ventilation, initiated in the ED, is associated with reduced pulmonary complications. An intervention cohort of 513 mechanically ventilated adult ED patients will be compared with over 1000 preintervention control patients. The primary outcome is a composite outcome of pulmonary complications after admission (ARDS and VACs). Multivariable logistic regression with propensity score adjustment will test the hypothesis that ED lung-protective ventilation decreases the incidence of pulmonary complications. ETHICS AND DISSEMINATION: Approval of the study was obtained prior to data collection on the first patient. As the study is a before-after observational study, examining the effect of treatment changes over time, it is being conducted with waiver of informed consent. This work will be disseminated by publication of full-length manuscripts, presentation in abstract form at major scientific meetings and data sharing with other investigators through academically established means. TRIAL REGISTRATION NUMBER: NCT02543554

Development of Bullous Pemphigoid While Receiving PD-1 Checkpoint Inhibitor Nivolumab

Monoclonal antibodies against PD-1 are becoming increasingly important agents in the oncologist's armamentarium against a variety of cancers, including melanoma and squamous cell carcinoma. Most reported cutaneous reactions to these agents are mild and resolve with a conservative treatment approach. We present two cases of patients treated with anti-PD-1 agents who developed bullous pemphigoid shortly after initiation of therapy. We then review the literature of anti-PD-1-associated bullous pemphigoid, which is likely a bona fide side effect of anti-PD-1 therapy. Finally, we discuss management of these cases, where the risks of bullous pemphigoid must be weighed against the benefits of anti-PD-1 treatment. As the number of indications for PD-1 monoclonal antibodies expands, dermatologists will need to recognize their cutaneous adverse events and assist oncologists in the management of such complications.</jats:p

Water and Rock Chemistry Inform Our Understanding of the Deep Biosphere: Case Study in an Archaean Banded Iron Formation

Research into the deep biosphere requires an understanding of both the microbial community at a given site and the geochemical and hydrological factors that support that microbial community. To highlight the interplay between geochemistry and microbiology in these deep environments, we characterized the hydrogeologic and geochemical systems of a 2.7 Ga banded iron formation within the Canadian Shield in the Soudan Underground Mine State Park in Minnesota, United States, a site known to host a lithotrophic microbial community. Calcium-sodium-chloride brines, characteristic of deep groundwaters throughout the Canadian Shield, were found in the site with total dissolved constituents (&amp;lt;0.2 micron) as high as 116,000 mg/L (ppm) in one borehole. Comparison of the Soudan waters to those found at other sites in the Canadian Shield or other sites of deep biosphere research indicate that they are notable for their high magnesium concentrations relative to total salinity. Additionally, the most saline Soudan waters have distinct 2H and 18O water isotope values suggesting long periods of isolation from the surface, which would allow for the evolution of a distinctive subsurface community. The presence of the banded iron formation along with the long-term isolation of the shield waters make Soudan a site of great potential for future research into deep crustal life. Furthermore, our work at Soudan highlights how geochemical data can inform future research into the deep biosphere and highlights a path for future research at the mine.</jats:p

DataSheet1_Water and Rock Chemistry Inform Our Understanding of the Deep Biosphere: Case Study in an Archaean Banded Iron Formation.docx

Research into the deep biosphere requires an understanding of both the microbial community at a given site and the geochemical and hydrological factors that support that microbial community. To highlight the interplay between geochemistry and microbiology in these deep environments, we characterized the hydrogeologic and geochemical systems of a 2.7 Ga banded iron formation within the Canadian Shield in the Soudan Underground Mine State Park in Minnesota, United States, a site known to host a lithotrophic microbial community. Calcium-sodium-chloride brines, characteristic of deep groundwaters throughout the Canadian Shield, were found in the site with total dissolved constituents (2H and 18O water isotope values suggesting long periods of isolation from the surface, which would allow for the evolution of a distinctive subsurface community. The presence of the banded iron formation along with the long-term isolation of the shield waters make Soudan a site of great potential for future research into deep crustal life. Furthermore, our work at Soudan highlights how geochemical data can inform future research into the deep biosphere and highlights a path for future research at the mine.</p

A Quasi-Experimental, Before-After Trial Examining the Impact of an Emergency Department Mechanical Ventilator Protocol on Clinical Outcomes and Lung-Protective Ventilation in Acute Respiratory Distress Syndrome

OBJECTIVE: To evaluate the impact of an emergency department (ED) mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome (ARDS). DESIGN: Quasi-experimental, before-after trial. SETTING: ED and intensive care units (ICU) of an academic center. PATIENTS: Mechanically ventilated ED patients experiencing ARDS while in the ED or after admission to the ICU. INTERVENTIONS: An ED ventilator protocol which targeted parameters in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume; 2) appropriate setting of positive end-expiratory pressure (PEEP); 3) oxygen weaning; and 4) head-of-bed elevation. MEASUREMENTS AND MAIN RESULTS: A total of 229 patients (186 pre-intervention group, 43 intervention group) were studied. In the ED, the intervention was associated with significant changes (P < 0.01 for all) in tidal volume, PEEP, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in ED tidal volume from 8.1 mL/kg PBW (7.0 – 9.1) to 6.4 mL/kg PBW (6.1 – 6.7), and an increase in lung-protective ventilation from 11.1% to 61.5%, P < 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (OR 0.38, 95% CI 0.17 – 0.83, P = 0.02), and a 3.9 day increase in ventilator-free days, P = 0.01. CONCLUSIONS: This before-after study of mechanically ventilated patients with ARDS demonstrates that implementing a mechanical ventilator protocol in the ED is feasible, and associated with improved clinical outcomes