Comparison of Treatment Approaches and Subsequent Outcomes within a Pulmonary Embolism Response Team Registry.

Objectives: To characterize the association between pulmonary embolism (PE) severity and bleeding risk with treatment approaches, outcomes, and complications. Methods: Secondary analysis of an 11-hospital registry of adult ED patients treated by a PE response team (August 2016-November 2022). Predictors were PE severity and bleeding risk. The primary outcome was treatment approach: anticoagulation monotherapy vs. advanced intervention (categorized as "immediate" or "delayed" based on whether the intervention was received within 12 hours of PE diagnosis or not). Secondary outcomes were death, clinical deterioration, and major bleeding. Results: Of the 1832 patients, 139 (7.6%), 977 (53.3%), and 9 (0.5%) were classified as high-risk, intermediate-high, intermediate-low, and low-risk severity, respectively. There were 94 deaths (5.1%) and 218 patients (11.9%) had one or more clinical deterioration events. Advanced interventions were administered to 86 (61.9%), 195 (27.6%), and 109 (11.2%) patients with high-risk, intermediate-high, and intermediate-low severity, respectively.Major bleeding occurred in 61/1440 (4.2%) on ACm versus 169/392 (7.6%) with advanced interventions (p <0.001): bleeding withcatheter-directed thrombolysiswas 19/145 (13.1%) versus 33/154(21.4%) with systemic thrombolysis,p= 0.07. High risk was twice as strong as intermediate-high risk for association with advanced intervention (OR: 5.3 (4.2 and 6.9) vs. 1.9 (1.6 and 2.2)). High risk (OR: 56.3 (32.0 and 99.2) and intermediate-high risk (OR: 2.6 (1.7 and 4.0)) were strong predictors of clinical deterioration. Major bleeding was significantly associated with advanced interventions (OR: 5.2 (3.5 and 7.8) for immediate, 3.3 (1.8 and 6.2)) for delayed, and high-risk PE severity (OR: 3.4 (1.9 and 5.8)). Conclusions: Advanced intervention use was associated with high-acuity patients experiencing death, clinical deterioration, and major bleeding with a trend towards less bleeding with catheter-directed interventions versus systemic thrombolysis.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.

PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Incidence, severity and detection of blood pressure and heart rate perturbations in postoperative ward patients after noncardiac surgery.

STUDY OBJECTIVE: We sought to determine changes in continuous mean and systolic blood pressure and heart rate in a cohort of non-cardiac surgical patients recovering on the postoperative ward. Furthermore, we estimated the proportion of vital signs changes that would remain undetected with intermittent vital signs checks. DESIGN: Retrospective cohort. SETTING: Post-operative general ward. PATIENTS: 14,623 adults recovering from non-cardiac surgical procedures. INTERVENTIONS & MEASUREMENTS: Using a wireless, noninvasive monitor, we recorded postoperative blood pressure and heart rate at 15-s intervals and encouraged nursing intervention as clinically indicated. MAIN RESULTS: 7% of our cohort of 14,623 patients spent >15 sustained minutes with a MAP <65 mmHg, and 23% had MAP <75 mmHg for 15 sustained minutes. Hypertension was more common, with 67% of patients spending at least 60 sustained minutes with MAP >110 mmHg. Systolic pressures <90 mmHg were present for 15 sustained minutes in about a fifth of all patients, and 40% of patients had pressures >160 mmHg sustained for 30 min. 40% of patients were tachycardic with heart rates >100 beats/min for at least continuous 15 min and 15% of patients were bradycardic at a threshold of <50 beats/min for 5 sustained minutes. Conventional vital sign assessments at 4-h intervals would have missed 54% of mean pressure episodes <65 mmHg sustained >15 min, 20% of episodes of mean pressures >130 mmHg sustained >30 min, 36% of episodes of heart rate > 120 beats/min sustained <10 min, and 68% of episodes of heart rate sustained <40 beats per minute for >3 min. CONCLUSIONS: Substantial hemodynamic disturbances persisted despite implementing continuous portable ward monitoring coupled with nursing alarms and interventions. A significant proportion of these changes would have gone undetected using traditional intermittent monitoring. Better understanding of effective responses to alarms and appropriate interventions on hospital wards remains necessary.

Comparing predictive performance of pulmonary embolism risk stratification tools for acute clinical deterioration.

Objectives: Existing pulmonary embolism (PE) risk scores were developed to predict death within weeks, but not more proximate adverse events. We determined the ability of 3 PE risk stratification tools (simplified pulmonary embolism severity index [sPESI], 2019 European Society of Cardiology guidelines [ESC], and PE short-term clinical outcomes risk estimation [PE-SCORE]) to predict 5-day clinical deterioration after emergency department (ED) diagnosis of PE. Methods: We analyzed data from six EDs on ED patients with confirmed PE. Clinical deterioration was defined as death, respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension requiring vasopressors or volume resuscitation, or escalated intervention within 5 days of PE diagnosis. We determined sensitivity and specificity of sPESI, ESC, and PE-SCORE for predicting clinical deterioration. Results: Of 1569 patients, 24.5% had clinical deterioration within 5 days. sPESI, ESC, and PE-SCORE classifications were low-risk in 558 (35.6%), 167 (10.6%), and 309 (19.6%), respectively. Sensitivities of sPESI, ESC, and PE-SCORE for clinical deterioration were 81.8 (78, 85.7), 98.7 (97.6, 99.8), and 96.1 (94.2, 98), respectively. Specificities of sPESI, ESC, and PE-SCORE for clinical deterioration were 41.2 (38.4, 44), 13.7 (11.7, 15.6), and 24.8 (22.4, 27.3). Areas under the curve were 61.5 (59.1, 63.9), 56.2 (55.1, 57.3), and 60.5 (58.9, 62.0). Negative predictive values were 87.5 (84.7, 90.2), 97 (94.4, 99.6), and 95.1 (92.7, 97.5). Conclusions: ESC and PE-SCORE were better than sPESI for detecting clinical deterioration within 5 days after PE diagnosis.

A Pragmatic Pilot Trial Comparing Patient-Triggered Adaptive Pressure Control to Patient-Triggered Volume Control Ventilation in Critically Ill Adults.

BACKGROUND: Patient-triggered adaptive pressure control (APC) continuous mandatory ventilation (CMV) (APC-CMV) has been widely adopted as an alternative ventilator mode to patient-triggered volume control (VC) CMV (VC-CMV). However, the comparative effectiveness of the 2 ventilator modes remains uncertain. We sought to explore clinical and implementation factors pertinent to a future definitive randomized controlled trial assessing APC-CMV versus VC-CMV as an initial ventilator mode strategy. The research objectives in our pilot trial tested clinician adherence and explored clinical outcomes. METHODS: In a single-center pragmatic sequential cluster crossover pilot trial, we enrolled all eligible adults with acute respiratory failure requiring mechanical ventilation admitted during a 9-week period to the medical ICU. Two-week time epochs were assigned a priori in which subjects received either APC-CMV or VC-CMV The primary outcome of the trial was feasibility, defined as 80% of subjects receiving the assigned mode within 1 h of initiation of ICU ventilation. The secondary outcome was proportion of the first 24 h on the assigned mode. Finally, we surveyed clinician stakeholders to understand potential facilitators and barriers to conducting a definitive randomized trial. RESULTS: We enrolled 137 subjects who received 152 discreet episodes of mechanical ventilation during time epochs assigned to APC-CMV (n = 61) and VC-CMV (n = 91). One hundred and thirty-one episodes were included in the prespecified primary outcome. One hundred and twenty-six (96%) received the assigned mode within the first hour of ICU admission (60 of 61 subjects assigned APC-CMV and 66 of 70 assigned VC-CMV). VC-CMV subjects spent a lower proportion of first 24 h (84% [95% CI 78-89]) on the assigned mode than APC-CMV recipients (95% [95% CI 91-100]). Mixed-methods analyses identified preconceived perceptions of subject comfort by clinicians and need for real-time education to address this concern. CONCLUSIONS: In this pilot pragmatic, sequential crossover trial, unit-wide allocation to a ventilator mode was feasible and acceptable to clinicians.

Quality of life 1 month after acute pulmonary embolism in emergency department patients.

OBJECTIVE: The Pulmonary Embolism Quality-of-Life (PEmb-QoL) questionnaire assesses quality of life (QoL) after pulmonary embolism (PE). We aimed to determine whether any clinical or pathophysiologic features of PE were associated with worse PEmb-QoL scores 1 month after PE. METHODS: In this prospective multicenter registry, we conducted PEmb-QoL questionnaires. We determined differences in QoL domain scores for four primary variables: clinical deterioration (death, cardiac arrest, respiratory failure, hypotension requiring fluid bolus, catecholamine support, or new dysrhythmia), right ventricular dysfunction (RVD), PE risk stratification, and subsequent rehospitalization. For overall QoL score, we fit a multivariable regression model that included these four primary variables as independent variables. RESULTS: Of 788 PE patients participating in QoL assessments, 156 (19.8%) had a clinical deterioration event, 236 (30.7%) had RVD of which 38 (16.1%) had escalated interventions. For those without and with clinical deterioration, social limitations had mean (±SD) scores of 2.07 (±1.27) and 2.36 (±1.47), respectively (p = 0.027). For intensity of complaints, mean (±SD) scores for patients without RVD (4.32 ± 2.69) were significantly higher than for those with RVD with or without reperfusion interventions (3.82 ± 1.81 and 3.83 ± 2.11, respectively; p = 0.043). There were no domain score differences between PE risk stratification groups. All domain scores were worse for patients with rehospitalization versus without. By multivariable analysis, worse total PEmb-QoL scores with effect sizes were subsequent rehospitalization 11.29 (6.68-15.89), chronic obstructive pulmonary disease (COPD) 8.17 (3.91-12.43), and longer index hospital length of stay 0.06 (0.03-0.08). CONCLUSIONS: Acute clinical deterioration, RVD, and PE severity were not predictors of QoL at 1 month post-PE. Independent predictors of worsened QoL were rehospitalization, COPD, and index hospital length of stay.

Quasi-partial order continual reassessment method: Applying toxicity scores to cancer dose-finding drug combination trials.

The primary endpoint of most dose-finding cancer trials is patient toxicity, and the primary goal is to identify the maximum tolerated dose (MTD), that is, the highest dose that falls below or within a pre-specified toxicity tolerability threshold. Conventionally, dose-finding methods have utilized a binary toxicity endpoint based on whether or not a patient experiences a dose limiting-toxicity (DLT). Improving upon this, in recent years several methods have been developed for modeling toxicity scores, a novel continuous endpoint designed to more precisely estimate patient toxicity burden. Separately, drug-combination trials have become increasingly prevalent, and due to added complexities regarding estimating 'true' dose ordering and potential for more complex patient toxicity profiles, provide an ideal setting which may benefit from the improved precision of toxicity scores. In this paper, we merge two frameworks based on the Continual Reassessment Method (CRM) - the Quasi-CRM and the Partial Order CRM (POCRM) - to propose a novel approach for modeling toxicity scores in a combination-trial setting. We demonstrate that utilizing toxicity scores has the potential to greatly improve correct dose-selection over a variety of trial scenarios. We further present a simple adaptation to the toxicity-score model to control for potential over-dosing issues such that it adheres to the conventional DLT definition and will, at worst, perform equivalently to that of the traditional binary DLT framework. We demonstrate that extending toxicity scores to the combination-trial setting offers potential for improvement over the conventional binary endpoint models.

Characteristics of Adult Primary Care Patients Who Use the Patient Portal: A Cross-Sectional Analysis.

BACKGROUND: The patient portal allows patients to engage with their health care team beyond the clinical encounter. While portals can improve patient outcomes, there may be disparities in which patients access the portal by sociodemographic factors. Understanding the characteristics of patients who use the portal could help design future interventions to expand portal adoption. OBJECTIVES: This study aimed to (1) examine the socioeconomic factors, comorbid conditions, and health care utilization among patients of a large academic primary care network who are users and non-users of the patient portal; and (2) describe the portal functions most frequently utilized. METHODS: We included all adult patients at Atrium Health Wake Forest Baptist who had at least two primary care visits between 2018 and 2019. Patients' demographics, comorbidities, health care utilization, and portal function usage were extracted from the electronic health record and merged with census data (income, education, and unemployment) from the American Community Survey. A myWakeHealth portal user was defined as a patient who used a bidirectional portal function at least once during the study period. We used multivariable logistic regression to determine which patient characteristics were independently associated with being a portal user. RESULTS: Of the 178,720 patients who met inclusion criteria, 32% (N = 57,122) were users of myWakeHealth. Compared to non-users, users were more likely to be 18 to 64 years of age, female, non-Hispanic White, married, commercially insured, have higher disease burden, and have lower health care utilization. Patients residing in areas with the highest educational attainment had 51% higher odds of being a portal user than the lowest (p <0.001). Among portal users, the most commonly used function was messaging clinic providers. CONCLUSION: We found that patient demographics and area socioeconomic factors were associated with patient portal adoption. These findings suggest that efforts to improve portal adoption should be targeted at vulnerable patients.

Electrocardiographic findings associated with early clinical deterioration in acute pulmonary embolism.

OBJECTIVES: We sought to determine associations of early electrocardiogram (ECG) patterns with clinical deterioration (CD) within 5 days and with RV abnormality (abnlRV) by echocardiography in pulmonary embolism (PE). METHODS: In this prospective, multicenter study of newly confirmed PE patients, early echocardiography and initial ECG were examined. Initial ECG patterns included lead-specific ST-segment elevation (STE) or depression (STD), T-wave inversion (TWI), supraventricular tachycardia (SVT), sinus tachycardia, and right bundle branch block as complete (cRBBB) or incomplete (iRBBB). We defined CD as respiratory failure, hypotension, dysrhythmia, cardiac arrest, escalated PE intervention, or death within 5 days. We calculated odds ratios (ORs) for CD and abnlRV with univariate and full multivariate models in the presence of other variables. RESULTS: Of 1676 patients, 1629 (97.2%) had both ECG and GDE; 415/1676 (24.7%) had CD, and 529/1629 (32.4%) had abnlRV. AbnlRV had an OR for CD of 4.25 (3.35, 5.38). By univariable analysis, the absence of abnormal ECG patterns had OR for CD and abnlRV of 0.34 (0.26, 0.44; p < 0.001) and 0.24 (0.18, 0.31; p < 0.001), respectively. By multivariable analyses, one ECG pattern had a significant OR for CD: SVT 2.87 (1.66, 5.00). Significant ORS for abnlRV were: TWI V2-4 4.0 (2.64, 6.12), iRBBB 2.63 (1.59, 4.38), STE aVR 2.42 (1.58, 3.74), S1-Q3-T3 2.42 (1.70, 3.47), and sinus tachycardia 1.68 (1.14, 2.49). CONCLUSIONS: SVT was an independent predictor of CD. TWI V2-4 , iRBBB, STE aVR, sinus tachycardia, and S1-Q3-T3 were independent predictors of abnlRV. Finding one or more of these ECG patterns may increase considerations for performance of echocardiography to look for RV abnormalities and, if present, inform concerns for early clinical deterioration.

Intermediate-risk pulmonary embolism: echocardiography predictors of clinical deterioration.

BACKGROUND: We determine the predictive value of transthoracic echocardiographic (TTE) metrics for clinical deterioration within 5 days in adults with intermediate-risk pulmonary embolism (PE). METHODS: This was a prospective observational study of intermediate-risk PE patients. To determine associations of TTE and clinical predictors with clinical deterioration, we used univariable analysis, Youden's index for optimal thresholds, and multivariable analyses to report odds ratios (ORs) or area under the curve (AUC). RESULTS: Of 306 intermediate-risk PE patients, 115 (37.6%) experienced clinical deterioration. PE patients who had clinical deterioration within 5 days had greater baseline right ventricle (RV) dilatation and worse systolic function than the group without clinical deterioration as indicated by the following: RV basal diameter 4.46 ± 0.77 versus 4.20 ± 0.77 cm; RV/LV basal width ratio 1.14 ± 0.29 versus 1.02 ± 0.24; tricuspid annular plane systolic excursion (TAPSE) 1.56 ± 0.55 versus 1.80 ± 0.52 cm; and RV systolic excursion velocity 10.40 ± 3.58 versus 12.1 ± 12.5 cm/s, respectively. Optimal thresholds for predicting clinical deterioration were: RV basal width 3.9 cm (OR 2.85 [1.64, 4.97]), RV-to-left ventricle (RV/LV) ratio 1.08 (OR 3.32 [2.07, 5.33]), TAPSE 1.98 cm (OR 3.3 [2.06, 5.3]), systolic excursion velocity 10.10 cm/s (OR 2.85 [1.75, 4.63]), and natriuretic peptide 190 pg/mL (OR 2.89 [1.81, 4.62]). Significant independent predictors were: transient hypotension 6.1 (2.2, 18.9), highest heart rate 1.02 (1.00, 1.03), highest respiratory rate 1.02 (1.00, 1.04), and RV/LV ratio 1.29 (1.14, 1.47). By logistic regression and random forest analyses, AUCs were 0.80 (0.73, 0.87) and 0.78 (0.70, 0.85), respectively. CONCLUSIONS: Basal RV, RV/LV ratio, and RV systolic function measurements were significantly different between intermediate-risk PE patients grouped by subsequent clinical deterioration.

Can right ventricular assessments improve triaging of low risk pulmonary embolism?

OBJECTIVES: Identifying right ventricle (RV) abnormalities is important to stratifying pulmonary embolism (PE) severity. Disposition decisions are influenced by concerns about early deterioration. Triaging strategies, like the Simplified Pulmonary Embolism Severity Index (sPESI), do not include RV assessments as predictors or early deterioration as outcome(s). We aimed to (1) determine if RV assessment variables add prognostic accuracy for 5-day clinical deterioration in patients classified low risk by sPESI, and (2) determine the prognostic importance of RV assessments compared to other variables and to each other. METHODS: We identified low risk sPESI patients (sPESI = 0) from a prospective PE registry. From a large field of candidate variables, we developed, and compared prognostic accuracy of, full and reduced random forest models (with and without RV assessment variables, respectively) on a validation database. We reported variable importance plots from full random forest and provided odds ratios for statistical inference of importance from multivariable logistic regression. Outcomes were death, cardiac arrest, hypotension, dysrhythmia, or respiratory failure within 5 days of PE. RESULTS: Of 1736 patients, 610 (35.1%) were low risk by sPESI and 72 (11.8%) experienced early deterioration. Of the 610, RV abnormality was present in 157 (25.7%) by CT, 121 (19.8%) by echocardiography, 132 (21.6%) by natriuretic peptide, and 107 (17.5%) by troponin. For deterioration, the receiver operating characteristics for full and reduced random forest prognostic models were 0.80 (0.77-0.82) and 0.71 (0.68-0.73), respectively. RV assessments were the top four in the variable importance plot for the random forest model. Echocardiography and CT significantly increased predicted probability of 5-day clinical deterioration by the multivariable logistic regression. CONCLUSIONS: A PE triaging strategy with RV imaging assessments had superior prognostic performance at classifying low risk for 5-day clinical deterioration versus one without.

Patient Characteristics Associated With Missed Appointments in Pediatric Subspecialty Clinics.

OBJECTIVES: Missed appointments negatively affect patients, providers, and health systems. This study aimed to (1) quantify the percentage of missed appointments across 14 pediatric subspecialties in a tertiary-care children's hospital and (2) identify patient characteristics associated with missed appointments in those subspecialties. METHODS: We extracted patient characteristics from 267,151 outpatient appointments, between January 1, 2013, and December 31, 2018, across 14 subspecialty clinics. Medical complexity was categorized using the Pediatric Medical Complexity Algorithm. The primary outcome was appointment nonattendance. Cancellations, imaging/laboratory visits, patients older than 18 years, and duplicate visits were excluded. Characteristics associated with nonattendance were analyzed with chi-square tests and included in the multivariable model if p < .1. Missing data were addressed using random forest imputation, and assuming data were "missing at random." Variables were considered statistically significant if p < .05. RESULTS: Of the 128,117 scheduled appointments analyzed, 23,204 (18.1%) were missed. In the multivariable model, clinical nutrition had the greatest subspecialty odds of missed appointments, whereas cardiology had the lowest. Patient characteristics most strongly associated with missed appointments were public insurance, history of >2 missed appointments, appointment lead time, lesser medical complexity, Black race/ethnicity, and fewer medications. CONCLUSIONS: Clinical characteristics including lesser medical complexity and fewer medications are associated with missed appointments in pediatric subspecialties.

Tolerability of bevacizumab and chemotherapy in a phase 3 clinical trial with human epidermal growth factor receptor 2-negative breast cancer: A trajectory analysis of adverse events.

BACKGROUND: E5103 was a study designed to evaluate the efficacy and safety of bevacizumab. It was a negative trial for the end points of invasive disease-free survival and overall survival. The current work examines the tolerability of bevacizumab and other medication exposures with respect to clinical outcomes and patient-reported outcomes (PROs). METHODS: Adverse events (AEs) collected from the Common Terminology Criteria for Adverse Events were summarized to form an AE profile at each treatment cycle. All-grade and high-grade events were separately analyzed. The change in the AE profile over the treatment cycle was delineated as distinct AE trajectory clusters. AE-related and any-reason early treatment discontinuations were treated as clinical outcome measures. PROs were measured with the Functional Assessment of Cancer Therapy-Breast + Lymphedema. The relationships between the AE trajectory and early treatment discontinuation as well as PROs were analyzed. RESULTS: More than half of all AEs (57.5%) were low-grade. A cluster of patients with broad and mixed AE (all-grade) trajectory grades was significantly associated with any-reason early treatment discontinuation (odds ratio [OR], 2.87; P = .01) as well as AE-related discontinuation (OR, 4.14; P = .001). This cluster had the highest count of all-grade AEs per cycle in comparison with other clusters. Another cluster of patients with primary neuropathic AEs in their trajectories had poorer physical well-being in comparison with a trajectory of no or few AEs (P < .01). A high-grade AE trajectory did not predict discontinuations. CONCLUSIONS: A sustained and cumulative burden of across-the-board toxicities, which were not necessarily all recognized as high-grade AEs, contributed to early treatment discontinuation. Patients with neuropathic all-grade AEs may require additional attention for preventing deterioration in their physical well-being.

Detection of Environmental Spread of SARS-CoV-2 and Associated Patient Characteristics.

Understanding transmission of severe acute respiratory syndrome coronavirus 2 informs infection prevention practices. Air sampling devices were placed in patient hospital rooms for consecutive collections with and without masks. With patient mask use, no virus was detected in the room. High viral load and fewer days from symptom onset were associated with viral particulate dispersion.