Faculty Bibliography

Background/UNASSIGNED:The COVID-19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID-19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow-up trial using the widely available tissue-plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective/UNASSIGNED:To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods/UNASSIGNED:A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO2 ratio<150mmHg for >4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re-dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results/UNASSIGNED:The primary outcome is improvement in PaO2/FiO2 at 48 hours post-randomization. Other outcomes include: ventilator- and ICU-free-days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped-wedge design with four looks at the data. Conclusion/UNASSIGNED:Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634).

A hallmark of severe COVID-19 is coagulopathy, with 71.4% of patients who die of COVID-19 meeting ISTH criteria for disseminated intravascular coagulation (DIC) while only 0.6% of patients who survive meet these criteria (1). Additionally, it has become clear that this is not a bleeding diathesis but rather a predominantly pro-thrombotic DIC with high venous thromboembolism rates, elevated D-dimer levels, high fibrinogen levels in concert with low anti-thrombin levels, and pulmonary congestion with microvascular thrombosis and occlusion on pathology in addition to mounting experience with high rates of central line thrombosis and vascular occlusive events (e.g. ischemic limbs, strokes, etc.) observed by those who care for critically ill COVID-19 patients (1-7). There is evidence in both animals and humans that fibrinolytic therapy in Acute Lung Injury and ARDS improves survival, which also points to fibrin deposition in the pulmonary microvasculature as a contributory cause of ARDS and would be expected to be seen in patients with ARDS and concomitant diagnoses of DIC on their laboratory values such as what is observed in more than 70% of those who die of COVID-19 (8-10).

Importance/UNASSIGNED:There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective/UNASSIGNED:To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants/UNASSIGNED:Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures/UNASSIGNED:Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures/UNASSIGNED:Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results/UNASSIGNED:A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance/UNASSIGNED:This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

BACKGROUND:Although home telemonitoring (TM) is a promising approach for patients managing their chronic disease, rehabilitation using home TM has not been tested for use with individuals living with chronic obstructive pulmonary disease (COPD) residing in underserved communities. OBJECTIVE:This study aimed to analyze qualitative data from focus groups with key stakeholders to ensure the acceptability and usability of the TM COPD intervention. METHODS:We utilized a community-based participatory research (CBPR) approach to adapt a home TM COPD intervention to facilitate acceptability and feasibility in low-income African American and Hispanic patients. The study engaged community stakeholders in the process of modifying the intervention in the context of 2 community advisory board meetings. Discussions were audio recorded and professionally transcribed and lasted approximately 2 hours each. Structural coding was used to mark responses to topical questions in interview guides. RESULTS:We describe herein the formative process of a CBPR study aimed at optimizing telehealth utilization among African American and Latino patients with COPD from underserved communities. A total of 5 major themes emerged from qualitative analyses of community discussions: equipment changes, recruitment process, study logistics, self-efficacy, and access. The identification of themes was instrumental in understanding the concerns of patients and other stakeholders in adapting the pulmonary rehabilitation (PR) home intervention for acceptability for patients with COPD from underserved communities. CONCLUSIONS:These findings identify important adaptation recommendations from the stakeholder perspective that should be considered when implementing in-home PR via TM for underserved COPD patients. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03007485; https://clinicaltrials.gov/ct2/show/NCT03007485.

Background/UNASSIGNED:The need for life-saving interventions such as mechanical ventilation may threaten to outstrip resources during the Covid-19 pandemic. Allocation of these resources to those most likely to benefit can be supported by clinical prediction models. The ethical and practical considerations relevant to predictions supporting decisions about microallocation are distinct from those that inform shared decision-making in ways important for model design. Main body/UNASSIGNED:We review three issues of importance for microallocation: (1) Prediction of benefit (or of medical futility) may be technically very challenging; (2) When resources are scarce, calibration is less important for microallocation than is ranking to prioritize patients, since capacity determines thresholds for resource utilization; (3) The concept of group fairness, which is not germane in shared decision-making, is of central importance in microallocation. Therefore, model transparency is important. Conclusion/UNASSIGNED:Prediction supporting allocation of life-saving interventions should be explicit, data-driven, frequently updated and open to public scrutiny. This implies a preference for simple, easily understood and easily applied prognostic models.

Objectives: In New York City, asthma prevalence is greater in Hispanics than non-Hispanics for both children (10.9% vs. 7.4%) and adults (9.0% vs. 6.3%). Disparities in asthma management among Hispanics are found to arise, in part, from a limited education on asthma. Using elements of Community Based Participatory Research (CBPR), we worked with the community to identify asthma priorities and misconceptions among Hispanics and used that information to develop a tailored asthma educational tool-the Asthma Training Modules (ATMs).Methods: Over the past 3 years (2016, 2017, and 2018), we conducted educational asthma workshops to collect and analyze information to develop the ATMs and a summary of the ATMs in an Asthma Educational Card (AEC). We trained 6 Asthma-Community-Leaders using the ATMs, who assembled community members for teaching sessions using the AEC. Participants completed a pre-and-post asthma knowledge questionnaire.Results: We identified asthma priorities and misconceptions themed on: culturally relevant resources for Hispanics, symptom and trigger recognition, and treatments. A total of 104 participants attended the teaching sessions led by Asthma-Community-Leaders and participants' mean knowledge score increased from 64% pre-teaching to 85% post-teaching, (p < 0.01).Conclusion: Our community-led education, which included a tailored asthma educational tool and trained Asthma-Community-Leaders, successfully improved asthma knowledge among Hispanics. Further studies are warranted to determine whether these results are reproducible among a larger cohort and what the comparative effectiveness of our intervention as compared to other education-based interventions.

OBJECTIVE:To assess information needs of adults with Cystic Fibrosis and their families toward designing a patient decision aid about invasive mechanical ventilation (IMV) and lung transplant. METHODS:Focus groups and in-depth interviews explored participants' knowledge, prior clinical conversations, and decisions about IMV and lung transplant. Interviews and focus groups were recorded and transcribed for analysis. RESULTS:N = 24 participants were recruited. Themes identified were: prior communication with clinicians, decision-making process, and living with CF. Participants having prior conversations with CF clinicians regarding: lung transplant (N = 17/74%), and IMV (N = 3/13%). Most 15(65%) felt it was important to hear patients' real-life experience, others (3/13%) relied on their CF doctors for information. Most people (16/70%) believed hearing prognosis was helpful, but 5(22%) found this information frightening. High degrees of social isolation and a desire for more interaction with other CF adults were found. CONCLUSIONS:Qualitative methods helped identify areas important for decision making about IMV and LT for CF adults. Future directions include usability and feasibility testing of the decision aid. PRACTICE IMPLICATIONS/CONCLUSIONS:Because IMV is rarely discussed with CF adults, clinicians might approach this topic, as with transplant, as lung function begins to decline. CF-care teams should also foster CF patient-level information exchange.

BACKGROUND:Complementary and alternative medicines (CAM) are associated with poor asthma medication adherence, a major risk factor for asthma exacerbation. However, previous studies showed inconsistent relationships between CAM use and asthma control due to small sample sizes, demographic differences across populations studied, and poor differentiation of CAM types. METHODS:We examined associations between CAM use and asthma exacerbation using a cross-sectional analysis of the 2012 National Health Interview Survey. We included adults ≥18 years with current asthma (n = 2,736) to analyze racial/ethnic differences in CAM use as well as the association between CAM use and both asthma exacerbation and emergency department (ED) visit for asthma exacerbation across racial/ethnic groups. We ran descriptive statistics and multivariable logistic regressions. RESULT/RESULTS:Blacks (OR = 0.63 [0.49-0.81]) and Hispanics (OR = 0.66 [0.48-0.92]) had decreased odds of using CAM compared to Whites. Overall, there was no association between CAM use and asthma exacerbation (OR = 0.99 [0.79-1.25]) but the subgroup of 'other complementary approaches' was associated with increased odds of asthma exacerbation among all survey respondents (1.90 [1.21-2.97]), Whites (OR = 1.90 [1.21-2.97]), and Hispanics (OR = 1.43 [0.98-2.09). CAM use was associated with decreased odds of an ED visit for asthma exacerbation (OR = 0.65 [0.45-0.93]). These associations were different among racial/ethnic groups with decreased odds of ED visit among Whites (OR = 0.50 [0.32-0.78]) but no association among Blacks and Hispanics. CONCLUSION/CONCLUSIONS:We found that both CAM use and the association between CAM use and asthma exacerbation varied by racial/ethnic group. The different relationship may arise from how CAM is used to complement or to substitute for conventional asthma management.