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Discovery Grant Recipients


Brian M. Varisco, MD
Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

Topic: Multi-Omic Approach to Identifying PARDS Endotypes

Abstract: Acute respiratory distress syndrome (ARDS) and pediatric ARDS (PARDS) are severe, rapid- onset lung injury conditions that can arise following surgery, infection, or severe injury. ARDS and PARDS typically require prolonged admission to the intensive care unit and are associated with substantial morbidity, mortality, and medical costs. Very few therapies have been shown to be effective, and researchers have had modest success determining subtypes of ARDS and PARDS that might respond better to different therapies. To better identify the different biological categories of PARDS (termed endotypes), we have undertaken a study using nasal epithelial cell gene expression to categorize patients with PARDS. In diseases such as asthma, lung cancer, and chronic obstructive pulmonary disease, nasal epithelial cell gene expression has been predictive of lung pathology. Preliminary results show that this technique accurately identifies patients who go on to experience an uncomplicated PARDS course and identified two patients with complicated course and different gene expression profiles. We are currently funded to perform this study at our institution. This proposal: 1) expands our study to the Children’s Hospital of Philadelphia (CHOP), 2) integrates findings from both our institution and CHOP with findings of a PARDS peripheral blood transcriptomic endotyping study, 3) generates data necessary for planning future, multisite trials, and 4) investigates how two additional techniques (assay for transposase-accessible chromatin sequencing (ATAC-seq) of nasal brushings and proteomic analysis of expiratory limb filters might complement the mRNA-seq approach. The findings from this study will help us plan a definitive endotyping study that will include adult patients with ARDS and ultimately help clinicians better execute clinical trials in ARDS and PARDS and better care for critically ill patients with ARDS and PARDS.

Amelia BarwiseAmelia Barwise, MB, BCh, BAO
Mayo Clinic

Topic: Nested Observational Cohort to Evaluate Diagnostic Error and Delay in the Critically Ill

Abstract: Despite the recognition that diagnostic errors and delays are major contributors to preventable deaths and avoidable illness in the United States, little progress has been made in understanding the risk factors, prevalence, and impact on mortality and morbidity outcomes. Although there is a considerable body of literature outlining contributing causes, an effective strategy leading to a meaningful reduction in diagnostic error and delay rates has not made its way into practice. The process of reporting errors and near misses remains underdeveloped and lacks standardized measurement tools. Until the identification of diagnostic error improves so that timely inquiry can be performed, reductions in harm from diagnostic error and delay will be difficult to achieve. This proposal combines mixed methods research with comprehensive and systematic analysis of electronic health records (EHRs) to improve the identification of diagnostic error and delay in patients undergoing rapid response team (RRT) evaluations in four structurally and geographically diverse hospitals. We are seeking funds to conduct a nested observational multicenter cohort study to better understand diagnostic error and delay, a significant and understudied problem in healthcare. Using a previously retrospectively validated taxonomy-based EHR approach that successfully identifies diagnostic error and delay, we will prospectively screen hospitalized patients, triggering RRT activation. This enriched population has a high rate of diagnostic error and delay (5%-20%), according to our preliminary data and previously published studies. In parallel with external validation of the EHR approach, we will also engage clinicians and key stakeholders in mixed methods research to establish the factors that contribute to diagnostic error and delay and the potential solutions to reduce it. The information gained from this research will inform a future extramural funding application to test potential preventive strategies.


Lauren Van Scoy, MDLauren Van Scoy, MD
Penn State Milton S. Hershey Medical Center

Topic: Preparing Families for the Process of Shared Decision-Making During ICU Family Meetings

Abstract: Many studies have found that families find communication with clinicians in the intensive care unit (ICU) to be deeply flawed. This poor communication has significant health consequences for families, including long-term anxiety, depression, and posttraumatic distress disorder. The conceptual framework of shared decision-making (SDM) has been endorsed by many professional societies as an evidence-based communication strategy, suggesting that clinicians partner with family members during the decision-making process. To date, interventions intended to improve communication during the SDM process have focused on preparing clinicians for their side of the communication. Few interventions, however, prepare families for the stresses associated with decision-making. This is important to address because, only when families are emotionally and psychologically ready to engage with clinicians, can they be effective partners in SDM. This project will evaluate a novel tool for family members of ICU patients to use in advance of their first family meeting. Designed with emotionally overwhelmed family members in mind, the tool is an intentionally simple, open-ended workbook to allow families to acknowledge emotions and reflect before their family meeting so they can be effective partners during SDM. The workbook directly aligns with the SDM conceptual framework and the multiple goals theory of communication. This pilot project uses a mixed methods, randomized controlled design at two academic medical ICUs. Phase 1 involves a qualitative exploration of the tool’s acceptability and usability with family members of ICU patients to inform further refinement. Phase 2 involves a small, randomized controlled trial to evaluate feasibility and effectiveness outcomes, short-term efficacy, and contamination rates in the usual care group. The primary outcome is based on the Impact of Events Scale to assess stress and risk of posttraumatic stress disorder. Secondary outcomes are based on the family satisfaction in the ICU tool and Hospital Anxiety and Depression Scale. We will also begin to explore the relationship of attention to communication goals with the study outcomes. Communication assessments will include the Communication Quality Analysis tool and a determination of the extent to which SDM occurred. When the study aims are met, we will be prepared to apply for a National Institutes of Health R01 research grant to conduct a definitive randomized controlled trial aimed at better preparing family members for the stress of ICU decision-making and improving their long-term psychosocial health.

Tai PhanTài Pham, MD
St. Michael’s Hospital

Topic: Breathing Efforts in ARDS (BEARDS)

Abstract: Acute hypoxemic respiratory failure (AHRF) is one of the most frequent reasons to use invasive mechanical ventilation (MV) in the intensive care unit. Among potentially modifiable MV factors, the interaction between the patient and the ventilator (including the sedation delivered to control it) has raised major interest. MV is indispensable but can induce or worsen lung injury (ventilator-induced lung injury); the interaction between the delivered breaths and the patient’s spontaneous breathing activity can also create what has been recently referred to as patient self-inflicted lung injury. Asynchrony is also strongly associated with mortality. Additionally, respiratory muscle dysfunction potentially induced by MV can impact the weaning process. This multicenter study will focus on assessing patient-ventilator interaction and detecting specific asynchronies such as breath stacking, flow starvation, and reverse triggering, by continuously recording ventilator waveforms, indexes of respiratory drive, and patients’ clinical characteristics and outcomes. Patients with AHRF will be monitored with an esophageal catheter or by using diaphragm electrical activity with a neurally adjusted ventilatory assist catheter. Recordings will be made four times a day (for 30-60 minutes) for at least three days during patients’ first week of AHRF. The same software as is dedicated to dyssynchrony detection will be used to centralize and analyze patients’ interactions with the ventilator settings and patients’ spontaneous activity and measure patients’ efforts. Current and/or newly developed algorithms will be validated against a visual analysis of the waveforms. The study’s primary objective is to determine the incidence of each type of asynchrony in intubated hypoxemic patients, associated risk factors, and their relationship to outcomes. We will evaluate the delta between delivered ventilation and lung-protective ventilation across different ranges of severity as a result of these interactions and assess the impact on outcome. This will be the first large study of dyssynchrony epidemiology, informing the need to better control this factor, such as with neuromuscular blockers, implementing new monitoring techniques, titrating sedation on patients with high respiratory drive or using different MV settings. A better understanding of the impact of each type of dyssynchrony will eventually allow clinicians to personalize MV for each patient.