Faculty Bibliography

The need for therapeutic drug monitoring of direct oral anticoagulants (DOACs) remains an area of clinical equipoise. Although routine monitoring may be unnecessary given predictable pharmacokinetics in most patients, there may be altered pharmacokinetics in those with end organ dysfunction, such as those with renal impairment, or with concomitant interacting medications, at extremes of body weight or age, or in those with thromboembolic events in atypical locations. We aimed to assess real-world practices in situations in which DOAC drug-level monitoring was used at a large academic medical center. A retrospective review of the records of patients who had a DOAC drug-specific activity level checked from 2016 to 2019 was included. A total of 119 patients had 144 DOAC measurements (apixaban (n = 62) and rivaroxaban (n = 57)). Drug-specific calibrated DOAC levels were within an expected therapeutic range for 110 levels(76%), with 21 levels (15%) above the expected range and 13 levels (9%) below the expected range. The DOAC levels were checked in the setting of an urgent or emergent procedure in 28 patients (24%), followed by renal failure in 17 patients (14%), a bleeding event in 11 patients (9%), concern for recurrent thromboembolism in 10 patients (8%), thrombophilia in 9 patients (8%), a history of recurrent thromboembolism in 6 patients (5%), extremes of body weight in 7 patients (5%), and unknown reasons in 7 patients (5%). Clinical decision making was infrequently affected by the DOAC monitoring. Therapeutic drug monitoring with DOACs may help predict bleeding events in elderly patients, those with impaired renal function, and in the event of an emergent or urgent procedure. Future studies are needed to target the select patient-specific scenarios where monitoring DOAC levels may impact clinical outcomes.

Background: The introduction of electronic workflows has allowed for the flow of raw uncontextualized clinical data into medical documentation. As a result, many electronic notes have become replete of "noise" and deplete clinically significant "signals." There is an urgent need to develop and implement innovative approaches in electronic clinical documentation that improve note quality and reduce unnecessary bloating. Objective: This study aims to describe the development and impact of a novel set of templates designed to change the flow of information in medical documentation. Methods: This is a multihospital nonrandomized prospective improvement study conducted on the inpatient general internal medicine service across 3 hospital campuses at the New York University Langone Health System. A group of physician leaders representing each campus met biweekly for 6 months. The output of these meetings included (1) a conceptualization of the note bloat problem as a dysfunction in information flow, (2) a set of guiding principles for organizational documentation improvement, (3) the design and build of novel electronic templates that reduced the flow of extraneous information into provider notes by providing link outs to best practice data visualizations, and (4) a documentation improvement curriculum for inpatient medicine providers. Prior to go-live, pragmatic usability testing was performed with the new progress note template, and the overall user experience was measured using the System Usability Scale (SUS). Primary outcome measures after go-live include template utilization rate and note length in characters. Results: In usability testing among 22 medicine providers, the new progress note template averaged a usability score of 90.6 out of 100 on the SUS. A total of 77% (17/22) of providers strongly agreed that the new template was easy to use, and 64% (14/22) strongly agreed that they would like to use the template frequently. In the 3 months after template implementation, general internal medicine providers wrote 67% (51,431/76,647) of all inpatient notes with the new templates. During this period, the organization saw a 46% (2768/6191), 47% (3505/7819), and 32% (3427/11,226) reduction in note length for general medicine progress notes, consults, and history and physical notes, respectively, when compared to a baseline measurement period prior to interventions. Conclusions: A bundled intervention that included the deployment of novel templates for inpatient general medicine providers significantly reduced average note length on the clinical service. Templates designed to reduce the flow of extraneous information into provider notes performed well during usability testing, and these templates were rapidly adopted across all hospital campuses. Further research is needed to assess the impact of novel templates on note quality, provider efficiency, and patient outcomes.

UNLABELLED:Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES/OBJECTIVE:To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS/METHODS:Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES/METHODS:Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS:single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Cardiovascular morbidity and mortality occur with an extraordinarily high incidence in the hemodialysis-dependent end-stage kidney disease population. There is a clear need to improve identification of those individuals at the highest risk of cardiovascular complications in order to better target them for preventative therapies. Twelve-lead electrocardiograms are ubiquitous and use inexpensive technology that can be administered with minimal inconvenience to patients and at a minimal burden to care providers. The embedded waveforms encode significant information on the cardiovascular structure and function that might be unlocked and used to identify at-risk individuals with the use of artificial intelligence techniques like deep learning. In this review, we discuss the experience with deep learning-based analysis of electrocardiograms to identify cardiovascular abnormalities or risk and the potential to extend this to the setting of dialysis-dependent end-stage kidney disease.

INTRODUCTION: Ventilatory ratio (VR) is a bedside index of impaired ventilation that can be used as a surrogate marker for pulmonary dead space fraction (VD/VT). Vasculopathy is hypothesized to increase VD/VT in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. The purpose of this study was to investigate associations between VR and markers of inflammation in critically ill COVID-ARDS patients.
METHOD(S): We conducted a retrospective study of patients admitted to an intensive care unit due to SARS-CoV-2 infection. All subjects required invasive mechanical ventilation and met the Berlin criteria for ARDS. Clinical lab values were collected at two timepoints: 2-8 hours after intubation (T1) and 2-24 hours before tracheostomy (T2). VR was split into high (VR>2) and low (VR< 2) groups. Comparisons were performed using student's t, Mann-Whitney, and z tests for difference in proportions with alpha=0.05.
RESULT(S): Of the 139 subjects enrolled at T1, 67 (48%) had high VR (>2), with an overall mean VR of 2.08. High VR was significantly associated with leukocyte count (WBC) (13.3 vs. 10.6 x10^9/L, p=0.004), and platelet count (284 vs 248 x10^9/L, p=0.003). There was no association between VR status and procalcitonin (p=0.08), d-dimer (p=0.73), fibrinogen (p=0.38), CRP (p=0.22), and ferritin (p=0.33). Since certain markers had non-Gaussian distributions, we determined threshold values. D-dimer over 500 ng/mL was associated with higher VR (2.3 vs. 1.8, p=0.004) and procalcitonin over 0.5 ng/mL was moderately associated with higher VR (2.2 vs 1.9, p=0.052). CRP >181 mug/mL (the median) and ferritin values >1.5x the upper limit of normal were not associated with VR (p=0.30 and p=0.26, respectively). To enrich the dataset, we pooled data from T1 and T2 and treated each as an independent sample. In this pooled analysis, high VR was associated with higher platelet count (282 vs. 253, p=0.046), and higher procalcitonin (3.464 vs. 0.964, p=0.032). There were no significant associations with VR and d-dimer (p=0.88), fibrinogen (p=0.54), CRP (p=0.20), and ferritin (p=0.76) in the pooled data.
CONCLUSION(S): Ventilatory ratio appears to be associated with higher levels of some inflammatory markers including WBC, platelets, d-dimer, and procalcitonin in COVID-ARDS patients

INTRODUCTION: Mortality and morbidity associated with COVID-19 acute respiratory distress syndrome (ARDS) has been associated with pulmonary vasculopathy, which has been hypothesized to increase pulmonary dead space (VD/ VT). However, VD/VT is rarely measured at the bedside. As a result, multiple proxy estimates have been developed. Our hypothesis was proxy estimates for VD/VT would have differing utilities in prognostication of COVID-19 ARDS.
METHOD(S): We conducted a retrospective cohort study of patients admitted to an intensive care unit with SARSCoV- 2 ARDS who required invasive mechanical ventilation. Ventilation parameters were collected 2-8 hours after intubation. The VD/Vt proxies examined were 1) ventilatory ratio (VR), 2) estimation of VD/VT using the Harris-Benedict equation for energy expenditure (VD/VT-HB), 3) direct estimation of VD/VT using Beitler et. al.'s formula (VD/VTDir), and 4) corrected minute ventilation (VECorr). For each proxy, subjects were dichotomized using the median value. Comparisons were performed using the Wilcoxon rank-sum test with alpha=0.05.
RESULT(S): For 139 subjects, mean VR was 2.08 (SD+/-0.80), mean VD/VT-HB was 0.614 (+/-0.15), mean VD/VT-Dir was 0.657 (+/-0.08), and mean VECorr was 12.2 (+/-4.6) L/min. All four proxies had strong inter-measure correlation (Pearson's r 0.748-0.881, p< 0.001 for all comparisons). No proxy was predictive of 30-day hospital mortality. High VR and VECorr were associated with increased morbidity using a composite endpoint of death or organ failure (defined as requiring renal dialysis or extracorporeal membrane oxygenation) with both having an odds ratio of 2.20 (95% CI: 1.12-4.33, p=0.022), while VD/VT-HB (p=0.552) and VD/VT-Dir (p=0.554) were not significantly associated. Of all proxies, only VR was significantly associated with increased sequential organ failure assessment (SOFA) score at 10+/-4 days post-intubation (6.2 vs. 4.8, p=0.024) and more ventilatorfree days within the 30 days after intubation (3.2 vs. 1.8, p=0.029).
CONCLUSION(S): Ventilatory ratio and corrected minute volume appear to have stronger associations with morbidity in COVID-19 ARDS compared to other VD/VT estimates. Ventilatory ratio is also associated with ventilator-free days and delayed SOFA score

INTRODUCTION: Ventilatory ratio (VR) is a simple bedside index of carbon dioxide removal. VR correlates well with physiologic dead space fraction (VD/VT) and clinical outcomes in patients with acute respiratory distress syndrome (ARDS). We hypothesized that high VR would identify COVID-19 ARDS patients with higher risk for death and organ failure.
METHOD(S): We conducted a retrospective cohort study of patients admitted to a single hospital in New York, NY, USA from March-July 2020 who had PCR-confirmed SARS-CoV-2 infection, met the Berlin criteria for ARDS, and required tracheostomy for prolonged invasive mechanical ventilation (MV). MV parameters were collected 2-8 hours after intubation. Based on prior studies, a VR>2 was considered to be abnormally elevated. Comparisons were performed using the Wilcoxon rank-sum test or z-test for difference in proportions with alpha=0.05. The primary outcome was 30- day mortality and the secondary outcome was a composite endpoint of death or organ failure defined as requiring renal replacement or extracorporeal membrane oxygenation (ECMO) during the hospitalization.
RESULT(S): Of 139 subjects enrolled, 67 (48.2%) had a VR>2. Low and high VR groups had similar baseline characteristics, including age (mean 58 years, SD +/-15.2), body mass index (30.1+/-6.69 kg/m2), simplified acute physiology score II (35.4+/-12.4), sequential organ failure assessment (SOFA) score (5.7+/-2.5), and a 19-point review of systemic disease history. High VR was not significantly associated with mortality (OR 0.92, p=0.827). However, high VR was associated with increased risk for the composite endpoint (OR 1.96, p=0.049) and independently identified patients with a higher risk of organ failure (OR 2.03, p=0.047). High VR was also associated with longer hospital length-of-stay for subjects who survived to discharge (52 vs. 43, p=0.035), more MV-free days within the 30 days after intubation (3.2 vs. 1.8, p=0.029), and higher SOFA score at 10+/-4 days post-intubation (6.2 vs. 4.8, p=0.024).
CONCLUSION(S): Ventilatory ratio identifies COVID-ARDS ventilated patients with increased risk for organ failure requiring advanced intervention, as well as patients who may require prolonged mechanical ventilation and hospitalization