Faculty Bibliography

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.

INTRODUCTION/UNASSIGNED:We sought to describe the demographic characteristics, clinical features, and outcomes of a cohort of patients who presented to our emergency departments with mpox (formerly known as monkeypox) infection between May 1-August 1, 2022. CASE SERIES/UNASSIGNED:We identified 145 patients tested for mpox, of whom 79 were positive. All positive cases were among cisgender men, and the majority (92%) were among men who have sex with men. A large number of patients (39%) were human immunodeficiency virus (HIV) positive. There was wide variation in emergency department (ED) length of stay (range 2-16 hours, median 4 hours) and test turnaround time (range 1-11 days, median 4 days). Most patients (95%) were discharged, although a substantial proportion (22%) had a return visit within 30 days, and 28% ultimately received tecrovirimat. CONCLUSION/UNASSIGNED:Patients who presented to our ED with mpox had similar demographic characteristics and clinical features as those described in other clinical settings during the 2022 outbreak. While there were operational challenges to the evaluation and management of these patients, demonstrated by variable lengths of stay and frequent return visits, most were able to be discharged.

OBJECTIVE:We examined drive times to outpatient substance use disorder treatment providers that provide contingency management (CM) and those that integrate CM with medication for opioid use disorder (MOUD) services in 6 US states. METHODS:We completed cross-sectional geospatial analysis among census tracts in Delaware, Louisiana, Massachusetts, North Carolina, New York, and West Virginia. We excluded census tracts with a population of zero. Using data from the 2020 Shatterproof substance use treatment facility survey, our outcome was the minimum drive time in minutes from the census tract mean center of population to the nearest outpatient CM provider, outpatient CM provider with MOUD services, and federally qualified health centers (FQHC). We stratified census tracts by 2010 Rural-Urban Commuting Area codes and by state. RESULTS:The population was greater than zero in 11,719 of 11,899 census tracts. The median drive time to the nearest CM provider was 12.2 [interquartile range (IQR), 7.0-23.5) minutes and the median drive time to the nearest CM provider increased from 9.7 (IQR, 6.0-15.0) minutes in urban census tracts to 38.8 (IQR, 25.4-53.0) minutes in rural ( H = 3683, P < 0.001). The median drive time increased to the nearest CM provider with MOUD services [14.2 (IQR, 7.9-29.5) minutes, W = 18,877, P < 0.001] and decreased to the nearest FQHC [7.9 (IQR, 4.3-13.6) minutes, W = 11,555,894, P < 0.001]. CONCLUSIONS:These results suggest limited availability of CM, particularly within rural communities and for patients needing concurrent CM and MOUD treatment. Our results suggest greater adoption of CM within FQHCs could reduce urban-rural disparities in CM availability.

Transcutaneous electrical nerve stimulation (TENS) effectively reduces pain in fibromyalgia (FM). The purpose of this study was to examine the influence of TENS use on pressure pain thresholds (PPT) and conditioned pain modulation (CPM) in individuals with FM using data from the Fibromyalgia Activity Study with TENS trial (NCT01888640). Individuals with FM were randomly assigned to receive active TENS, placebo TENS, or no TENS for 4 weeks. A total of 238 females satisfied the per-protocol analysis among the active TENS (n = 76), placebo TENS (n = 68), and no TENS (n = 94) groups. Following 4 weeks of group allocation, the active TENS group continued for an additional 4 weeks of active TENS totaling 8 weeks (n = 66), the placebo and no TENS groups transitioned to receive 4 weeks of active TENS (delayed TENS, n = 161). Assessment of resting pain, movement-evoked pain (MEP), PPT, and CPM occurred prior to and following active, placebo, or no TENS. There were no significant changes in PPT or CPM among the active TENS, placebo TENS, or no TENS groups after 4 weeks. Individuals who reported clinically relevant improvements in MEP (≥30% decrease) demonstrated increases in PPT (P < .001), but not CPM, when compared to MEP non-responders. There were no significant correlations among the change in PPT or CPM compared to MEP and resting pain following active TENS use (active TENS + delayed TENS). PPT and CPM may provide insight to underlying mechanisms contributing to pain; however, these measures may not relate to self-reported pain symptoms. PERSPECTIVE: Pressure pain threshold increased in individuals with clinically relevant improvement (≥30%) in MEP, indicating the clinical relevance of PPT for understanding mechanisms contributing to pain. CPM was not a reliable indicator of treatment response in MEP responders.

BACKGROUND:Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model. METHODS:Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested is: Implementation of RN-led iCPR tools will reduce antibiotic prescribing across diverse primary care settings. Specifically, this study aims to: (1) determine the impact of iCPRs on rapid strep test and chest x-ray ordering and antibiotic prescribing rates when used by RNs; (2) examine resource use patterns and cost-effectiveness of RN visits across diverse clinical settings; (3) determine the impact of iCPR-guided care on patient satisfaction; and (4) ascertain the effect of the intervention on RN and physician burnout. DISCUSSION:This study represents an innovative approach to using an iCPR model led by RNs and specifically designed to address inappropriate antibiotic prescribing. This study has the potential to provide guidance on the effectiveness of delegating care of low-acuity patients with ARIs to RNs to increase use of iCPRs and reduce antibiotic overprescribing for ARIs in outpatient settings. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04255303, Registered February 5 2020, https://clinicaltrials.gov/ct2/show/NCT04255303 .

Patients with preexisting autoimmune disease (pAID) are generally excluded from clinical trials for immune checkpoint inhibitors (ICIs) for cancer due to concern of flaring pAID. In this multi-center, retrospective observational study, we compared safety of ICI combination (two ICI agents) versus monotherapy in cancer patients with pAIDs. The primary outcome was time to AEs (immune-related adverse events (irAEs) and/or pAID flares), with progression-free survival (PFS) and overall survival as secondary outcomes. Sixty-four of 133 patients (48%) received ICI combination and 69 (52%) monotherapy. Most had melanoma (32%) and lung cancer (31%). Most common pAIDs were rheumatic (28%) and dermatologic (23%). Over a median follow-up of 15 months (95%CI, 11-18 mo), the cumulative incidence of any-grade irAEs was higher for combination compared to monotherapy (subdistribution hazard ratio (sHR) 2.27, 95%CI 1.35-3.82). No statistically significant difference was observed in high-grade irAEs (sHR 2.31 (0.95-5.66), P = .054) or the cumulative incidence of pAID flares. There was no statistically significant difference for melanoma PFS between combination versus monotherapy (23.2 vs. 17.1mo, P = .53). The combination group was more likely to discontinue or hold ICI, but > 50% of the combination group was still able to continue ICI therapy. No treatment-related deaths occurred. In our cohort with pAIDs, patients had a tolerable toxicity profile with ICI combination therapy. Our results support the use of ICI combination if deemed necessary for cancer therapy in patients with pAIDs, since the ICI toxicities were comparable to monotherapy, able to be effectively managed and mostly did not require ICI interruption.

This manuscript guides school nurses in addressing the unique needs of U.S. school-aged students and families with limited English proficiency (LEP). Owing to the increasing ethnic and racial diversity in U.S. K-12 schools, school nurses will likely encounter children and families with LEP. Students with LEP may be part of a family which immigrated to this country as permanent residents, are refugees, or asylum seekers. Some may be from migrant families who move throughout the region or country for work. School health services, including nursing services, may be the first and only health resource to which these children have consistent access. The availability and importance of language access services are highlighted, as well as tips for school nurses to advocate for language access resources, training for effective communication, understanding the legal landscape, and addressing cultural beliefs that influence health behaviors. Advocacy toward identifying the distinctive needs of families with LEP aims to help school nurses target equitable health outcomes.