Design and implementation of community consultation for research conducted under exception from informed consent regulations for the PreVent and the PreVent 2 trials: Changes over time and during the COVID-19 pandemic.

INTRODUCTION: Emergency clinical research has played an important role in improving outcomes for acutely ill patients. This is due in part to regulatory measures that allow Exception From Informed Consent (EFIC) trials. The Food and Drug Administration (FDA) requires sponsor-investigators to engage in community consultation and public disclosure activities prior to initiating an Exception From Informed Consent trial. Various approaches to community consultation and public disclosure have been described and adapted to local contexts and Institutional Review Board (IRB) interpretations. The COVID-19 pandemic has precluded the ability to engage local communities through direct, in-person public venues, requiring research teams to find alternative ways to inform communities about emergency research. METHODS: The PreVent and PreVent 2 studies were two Exception From Informed Consent trials of emergency endotracheal intubation, conducted in one geographic location for the PreVent Study and in two geographic locations for the PreVent 2 Study. During the period of the two studies, there was a substantial shift in the methodological approach spanning across the periods before and after the pandemic from telephone, to in-person, to virtual settings. RESULTS: During the 10 years of implementation of Exception From Informed Consent activities for the two PreVent trials, there was overall favorable public support for the concept of Exception From Informed Consent trials and for the importance of emergency clinical research. Community concerns were few and also did not differ much by method of contact. Attendance was higher with the implementation of virtual technology to reach members of the community, and overall feedback was more positive compared with telephone contacts or in-person events. However, the proportion of survey responses received after completion of the remote, live event was substantially lower, with a greater proportion of respondents having higher education levels. This suggests less active engagement after completion of the synchronous activity and potentially higher selection bias among respondents. Importantly, we found that engagement with local community leaders was a key component to develop appropriate plans to connect with the public. CONCLUSION: The PreVent experience illustrated operational advantages and disadvantages to community consultation conducted primarily by telephone, in-person events, or online activities. Approaches to enhance community acceptance included partnering with community leaders to optimize the communication strategies and trust building with the involvement of Institutional Review Board representatives during community meetings. Researchers might need to pivot from in-person planning to virtual techniques while maintaining the ability to engage with the public with two-way communication approaches. Due to less active engagement, and potential for selection bias in the responders, further research is needed to address the costs and benefits of virtual community consultation and public disclosure activities compared to in-person events.

Liberation From Mechanical Ventilation in the Cardiac Intensive Care Unit.

The prevalence of respiratory failure is increasing in the contemporary cardiac intensive care unit (CICU) and is associated with a significant increase in morbidity and mortality. For patients that survive their initial respiratory decompensation, liberation from invasive mechanical ventilation (IMV) and the decision to extubate requires careful clinical assessment and planning. Therefore, it is essential for the CICU clinician to know how to assess and manage the various stages of IMV liberation, including ventilator weaning, evaluation of extubation readiness, and provide post-extubation care. In this review, we provide a comprehensive approach to liberation from IMV in the CICU, including cardiopulmonary interactions relative to withdrawal from positive pressure ventilation, evaluation of readiness for and assessment of spontaneous breathing trials, sedation management to optimize extubation, strategies for patients at a high risk for extubation failure, and tracheostomy in the cardiovascular patient.

Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience.

The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications.

Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum.

BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5(0) C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness.