Implementation of Inpatient Electronic Consultations During the COVID-19 Crisis and Its Sustainability Beyond the Pandemic: Quality Improvement Study.

BACKGROUND: Limiting in-person contact was a key strategy for controlling the spread of the highly infectious novel coronavirus (COVID-19). To protect patients and staff from the risk of infection while providing continued access to necessary health care services, we implemented a new electronic consultation (e-consult) service that allowed referring providers to receive subspecialty consultations for patients who are hospitalized and do not require in-person evaluation by the specialist. OBJECTIVE: We aimed to assess the impact of implementing e-consults in the inpatient setting to reduce avoidable face-to-face referrals during the COVID-19 pandemic. METHODS: This quality improvement study evaluated all inpatient e-consults ordered from July 2020 to December 2022 at the University of California Irvine Medical Center. The impact of e-consults was assessed by evaluating use (eg, number of e-consults ordered), e-consult response times, and outcome of the e-consult requests (eg, resolved electronically or converted to the in-person evaluation of patient). RESULTS: There were 1543 inpatient e-consults ordered across 11 participating specialties. A total of 53.5% (n=826) of requests were addressed electronically, without the need for a formal in-person evaluation of the patient. The median time between ordering an e-consult and a specialist documenting recommendations in an e-consult note was 3.7 (IQR 1.3-8.2) hours across all specialties, contrasted with 7.3 (IQR 3.6-22.0) hours when converted to an in-person consult (P<.001). The monthly volume of e-consult requests increased, coinciding with surges of COVID-19 cases in California. After the peaks of the COVID-19 crisis subsided, the use of inpatient e-consults persisted at a rate well above the precrisis levels. CONCLUSIONS: An inpatient e-consult service was successfully implemented, resulting in fewer unnecessary face-to-face consultations and significant reductions in the response times for consults requested on patients who are hospitalized and do not require an in-person evaluation. Thus, e-consults provided timely, efficient delivery of inpatient consultation services for appropriate problems while minimizing the risk of direct transmission of the COVID-19 virus between health care providers and patients. The service also demonstrated its value as a tool for effective inpatient care coordination beyond the peaks of the pandemic leading to the sustainability of service and value.

Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children.

BACKGROUND: We previously showed that impulse oscillometry (IOS) indices of peripheral airway function are associated with asthma control in children. However, little data exist on whether dysfunction in the peripheral airways can predict loss of asthma control. OBJECTIVE: We sought to determine the utility of peripheral airway impairment, as measured by IOS, in predicting loss of asthma control in children. METHODS: Fifty-four children (age, 7-17 years) with controlled asthma were enrolled in the study. Spirometric and IOS indices of airway function were obtained at baseline and at a follow-up visit 8 to 12 weeks later. Physicians who were blinded to the IOS measurements assessed asthma control (National Asthma Education and Prevention Program guidelines) on both visits and prescribed no medication change between visits. RESULTS: Thirty-eight (70%) patients maintained asthma control between 2 visits (group C-C), and 16 patients had asthma that became uncontrolled on the follow-up visit (group C-UC). There was no difference in baseline spirometric results between the C-C and C-UC groups, except for FEV1/forced vital capacity ratio (86% vs 82%, respectively; P < .01). Baseline IOS results, including resistance of the respiratory system at 5 Hz (R5; 6.4 vs 4.3 cm H2O · L(-1) · s), frequency dependence of resistance (difference of R5 and resistance of the respiratory system at 20 Hz [R5-20]; 2.0 vs 0.7 cm H2O · L(-1) · s), and reactance area (13.1 vs 4.1 cm H2O · L(-1)), of group C-UC were significantly higher than those of group C-C (P < .01). Receiver operating characteristic analysis showed baseline R5-20 and reactance area effectively predicted asthma control status at the follow-up visit (area under the curve, 0.91 and 0.90). CONCLUSION: Children with controlled asthma who have increased peripheral airway IOS indices are at risk of losing asthma control.

Relating small airways to asthma control by using impulse oscillometry in children.

BACKGROUND: Previous reports suggest that the peripheral airways are associated with asthma control. Patient history, although subjective, is used largely to assess asthma control in children because spirometric results are many times normal values. Impulse oscillometry (IOS) is an objective and noninvasive measurement of lung function that has the potential to examine independently both small- and large-airway obstruction. OBJECTIVE: We sought to determine the utility of IOS in assessing asthma control in children. METHODS: Asthmatic and healthy children (6-17 years) were enrolled in the study. Spirometric and IOS (resistance of the respiratory system at 5 Hz [R5] and 20 Hz [R20], reactance of the respiratory system at 5 Hz [X5], resonant frequency of reactance [Fres], and area under the reactance curve between 5 Hz and Fres [reactance area {AX}]) values were collected in triplicate before and after a bronchodilator was administered. The physicians were blinded to the IOS measurements and assessed asthma control using American Thoracic Society guidelines. RESULTS: Small-airway IOS measurements, including the difference of R5 and R20 [R5-20], X5, Fres, and AX, of children with uncontrolled asthma (n = 44) were significantly different from those of children with controlled asthma (n = 57) and healthy children (n = 14), especially before the administration of a bronchodilator. However, there was no difference in large-airway IOS values (R20). No differences were found between children with controlled asthma and healthy children in any of the end points. Receiver operating characteristic analysis showed cut points for baseline R5-20 (1.5 cm H(2)O · L(-1) · s) and AX (9.5 cm H(2)O · L(-1)) that effectively discriminated controlled versus uncontrolled asthma (area under the curve, 0.86 and 0.84) and correctly classified more than 80% of the population. CONCLUSION: Uncontrolled asthma is associated with small-airways dysfunction, and IOS might be a reliable and noninvasive method to assess asthma control in children.

Cut points for Asthma Control Tests in Mexican children in Orange County, California.

BACKGROUND: The Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) are validated measures of asthma control in which a score of 19 is defined as uncontrolled according to published reports. However, different cut points may exist in different ethnic populations. OBJECTIVE: To determine the cut point for uncontrolled asthma in a Mexican descent population from Orange Country, California, compared with an age- and asthma severity-matched non-Hispanic cohort. METHODS: The C-ACT (in children 6-11 years old) and ACT (in children 12-17 years old) scores were collected from 151 children of Mexican descent and 48 non-Hispanic controls with mild-to-moderate asthma who lived in Orange County. Physicians were masked to C-ACT and ACT scores while assessing control based on National Asthma Education and Prevention program guidelines. The receiver operating characteristic method was used to examine the screening accuracy of the tests to detect uncontrolled asthma. The optimal cut points were selected by maximizing the total sensitivity and specificity. RESULTS: Cronbach α values for the C-ACT (0.76) and the ACT (0.80) confirmed that both tests were reliable in our study population. The C-ACT and ACT scores were statistically higher in children of Mexican descent than non-Hispanic children (P = .008). A cut point of 22 was optimal to detect uncontrolled asthma in children of Mexican descent 6 to 11 years old (group 1: sensitivity, 0.74; specificity, 0.86; area under the curve [AUC], 0.83) and children 12 to 17 years old (group 3: sensitivity, 0.78; specificity, 0.68; AUC, 0.79). For non-Hispanic controls, a cut point of 20 were optimal to detect uncontrolled asthma in children 6 to 11 years old (group 2: sensitivity, 0.70; specificity, 0.91; AUC, 0.86) and children 12 to 17 years old (group 4: sensitivity, 0.83; specificity, 0.87; AUC, 0.91). CONCLUSION: In this cross-ethnic validation study, children of Mexican descent in Orange County seem to underreport asthma symptoms compared with a non-Hispanic population and may require higher C-ACT and ACT cut points to detect uncontrolled asthma.

Clinical patterns in asthma based on proximal and distal airway nitric oxide categories.

BACKGROUND: The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'awNO (nl/s), maximum airway flux] and distal contributions [CANO (ppb), distal airway/alveolar NO concentration]. We hypothesized that J'awNO and CANO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features. METHODS: In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'awNO and CANO. RESULTS: J'awNO was not correlated with CANO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'awNO (>or= 1.5 nl/s) and CANO (>or= 2.3 ppb): Type I (normal J'awNO and CANO), Type II (elevated J'awNO and normal CANO), Type III (elevated J'awNO and CANO) and Type IV (normal J'awNO and elevated CANO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'awNO, but was not related to CANO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CANO (III and IV) had significantly worse asthma control and morbidity when compared to categories I and II. CONCLUSIONS: J'awNO and CANO reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CANO were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.

A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model.

The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows >100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2 +/- 0.80 parts/billion). Furthermore, CA(NO) from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.

S-nitrosoglutathione preserves platelet function during in vitro ventricular assist device circulation.

Complications (severe bleeding/thromboembolism) may occur during ventricular assist device (VAD) circulation, caused mainly by platelet dysfunction from platelet activation. We hypothesized that S-nitrosoglutathione (GSNO), having platelet activity preservation properties like nitric oxide (NO), may be a titratable agent to diminish platelet activation and thus preserve platelet function. Dose-response measurement of platelet aggregation by GSNO was performed using an aggregometer. GSNO (1,000 microM) caused inhibition of collagen and ristocetin induced aggregation by approximately 50%. Next, in vitro ventricular assist device (VAD) circulation was performed (over 48 hours using human whole blood), both without (control) and with GSNO (1,000 microM), and the aggregability of perfusate was measured at 0, 0.5, 1, 3, 6, 12, 24, and 48 hours. In control VAD circuits, collagen induced platelet aggregability gradually decreased and became significantly lower after 3 hours of circulation. With GSNO, platelet function did not significantly decrease until after 12 hours. Similar results were seen for ristocetin induced aggregation; control aggregation dropped significantly after 6 hours, but not until after 24 hours with GSNO. Liquid phase measurement of total nitrogen oxides (NO(T)) confirmed added GSNO maintained high perfusate NO(T) compared with control. GSNO is effective in preserving platelet aggregation during the first 12 to 24 hours in vitro and may be effective in preserving platelet function by inhibiting platelet activation during in vivo VAD circulation.

Rapid anastomosis of endothelial progenitor cell-derived vessels with host vasculature is promoted by a high density of cotransplanted fibroblasts.

To ensure survival of engineered implantable tissues thicker than approximately 2-3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, before implantation (prevascularization), is one potential strategy to achieve this aim. In this study, we developed three-dimensional engineered vessel networks in vitro by coculture of endothelial cells (ECs) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial progenitor cell-derived ECs (EPC-ECs) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared with 5-7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein ECs (HUVECs) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immune-compromised mice, however, revealed a dramatic difference in the ability of EPC-ECs and HUVECs to form anastomoses with the host vasculature. Vascular beds derived from EPC-ECs were perfused within 1 day of implantation, whereas no HUVEC vessels were perfused at day 1. Further, while almost 90% of EPC-EC-derived vascular beds were perfused at day 3, only one-third of HUVEC-derived vascular beds were perfused. In both cases, a high density of fibroblasts accelerated anastomosis by 2-3 days. We conclude that both EPC-ECs and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo.

An elevated bronchodilator response predicts large airway inflammation in mild asthma.

Exhaled nitric oxide (eNO) is elevated in asthmatics and is a purported marker of airway inflammation. The bronchodilator response (BDR) has also been shown to correlate with markers of airway inflammation, including eNO at 50 ml/sec (FE(NO,50)) which is comprised of NO from both the proximal and distal airways. Using eNO at multiple flows and a two-compartment model of NO exchange, the eNO signal can be partitioned into its proximal [J'aw(NO) (nl/sec)] and distal contributions [CA(NO) (ppb)]. We hypothesized that the BDR reflects the inflammatory status of the larger airways with smooth muscle, and thus would correlate with J'aw(NO). In 179 predominantly (95%) Hispanic children with mild asthma (69 steroid naïve), and 21 non-asthmatic non-atopic controls, spirometry and eNO at multiple flows were measured prior and 10 min following inhalation of albuterol. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'aw(NO) and CA(NO). The BDR correlated moderately (r = 0.44) with proximal airway NO (J'aw(NO)), but weakly (r = 0.26) with distal airway/alveolar NO (CA(NO)), and only in inhaled corticosteroid naïve asthmatics. A BDR cut point as low as >or=8% had a positive predictive value of 83% for predicting an elevated J'aw(NO) or FE(NO,50). We conclude that the BDR reflects inflammation in the large airways, and may be an effective clinical tool to predict elevated large airway inflammation.

Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature.

One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.

Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry.

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.