Reducing Overuse of 3-Day Repeat Type and Screen Testing across an 11-Hospital Safety Net System.

BACKGROUND: According to the American Association of Blood Banks, a Type and Screen (T&S) is valid for up to three calendar days. Beyond a limited number of clinical indications such as a transfusion reaction, repeat T&S testing within 3 days is not warranted. Inappropriate repeat T&S testing is a costly medical waste and can lead to patient harm. OBJECTIVE: To reduce inappropriate duplicate T&S testing across a large, multihospital setting. SETTING: The largest urban safety net health system in the USA, with 11 acute care hospitals. INTERVENTIONS: Our first intervention involved adding the time elapsed since the last T&S order into the order and the process instructions that described when a T&S was indicated. The second intervention was a best practice advisory that triggered when T&S was ordered before the expiration of an active T&S. MAIN MEASURES: The primary outcome measure was the number of duplicate inpatient T&S per 1000 patient days. KEY RESULTS: Across all hospitals, the weekly average rate of duplicate T&S ordering decreased from 8.42 to 7.37 per 1000 patient days (12.5% reduction, p < 0.001) after the first intervention and to 4.32 per 1000 patient days (48.7% reduction, p < 0.001) after the second intervention. Using linear regression to compare pre-intervention to post-intervention 1, the level difference was - 2.46 (9.17 to 6.70, p < 0.001) and slope difference was 0.0001 (0.0282 to 0.0283, p = 1). For post-intervention 1 to post-intervention 2, the level difference was - 3.49 (8.06 to 4.58, p < 0.001) and slope difference was - 0.0428 (0.0283 to - 0.0145, p < 0.05). CONCLUSIONS: Our intervention successfully reduced duplicate T&S testing using a two-pronged electronic health record intervention. The success of this low effort intervention across a diverse health system provides a framework for similar interventions in various clinical settings.

Challenges in interpreting cytokine data in COVID-19 affect patient care and management.

Challenges in using cytokine data are limiting Coronavirus Disease 2019 (COVID-19) patient management and comparison among different disease contexts. We suggest mitigation strategies to improve the accuracy of cytokine data, as we learn from experience gained during the COVID-19 pandemic.

Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide-induced oxidative stress.

This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.

Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.

Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC50 ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses.

Student High Value Care Initiative: a Longitudinal Model for Student-Led Implementation and Scholarship.

BACKGROUND: Educating medical trainees to practice high value care is a critical component to improving quality of care and should be introduced at the beginning of medical education. AIM: To create a successful educational model that provides medical students and junior faculty with experiential learning in quality improvement and mentorship opportunities, and produce effective quality initiatives. SETTING: A tertiary medical center affiliated with a medical school in New York City. PARTICIPANTS: First year medical students, junior faculty in hospital medicine, and a senior faculty course director. PROGRAM DESCRIPTION: The Student High Value Care initiative is a longitudinal initiative comprised of six core elements: (1) project development, (2) value improvement curriculum, (3) mentorship, (4), Institutional support, (5) scholarship, and (6) student leadership. PROGRAM EVALUATION: During the first 3 years, 68 medical students and ten junior faculty participated in 10 quality improvement projects. Nine projects were successful in their measured outcomes, with statistically significant improvements. Nine had an abstract accepted to a regional or national meeting, and seven produced publications in peer-reviewed literature. DISCUSSION: In the first 3 years of the initiative, we successfully engaged medical students and junior faculty to create and support the implementation of successful quality improvement initiatives. Since that time, the program continues to offer meaningful mentorship and scholarship opportunities.

Reducing 25-Hydroxyvitamin D Testing in a Large, Urban Safety Net System.

BACKGROUND: 25-Hydroxyvitamin D testing is increasing despite national guidelines and Choosing Wisely recommendations against routine screening. Overuse can lead to misdiagnosis and unnecessary downstream testing and treatment. Repeat testing within 3 months is a unique area of overuse. OBJECTIVE: To reduce 25-hydroxyvitamin D testing in a large safety net system comprising 11 hospitals and 70 ambulatory centers. DESIGN: This was a quality improvement initiative with a quasi-experimental interrupted time series design with segmented regression. PARTICIPANTS: All patients in the inpatient and outpatient settings with at least one order for 25-hydroxyvitamin D were included in the analysis. INTERVENTIONS: An electronic health record clinical decision support tool was designed for inpatient and outpatient orders and involved two components: a mandatory prompt requiring appropriate indications and a best practice advisory (BPA) focused on repeat testing within 3 months. MAIN MEASURES: The pre-intervention period (6/17/2020-6/13/2021) was compared to the post-intervention period (6/14/2021-8/28/2022) for total 25-hydroxyvitamin D testing, as well as 3-month repeat testing. Hospital and clinic variation in testing was assessed. Additionally, best practice advisory action rates were analyzed, separated by clinician type and specialty. KEY RESULTS: There were 44% and 46% reductions in inpatient and outpatient orders, respectively (p < 0.001). Inpatient and outpatient 3-month repeat testing decreased by 61% and 48%, respectively (p < 0.001). The best practice advisory true accept rate was 13%. CONCLUSION: This initiative successfully reduced 25-hydroxyvitamin D testing through the use of mandatory appropriate indications and a best practice advisory focusing on a unique area of overuse: the repeat testing within a 3-month interval. There was wide variation among hospitals and clinics and variation among clinician types and specialties regarding actions to the best practice advisory.

Spectroscopic and Chemical Properties of Ionic Liquids: Computational Study.

A brief account is given of highlights of our computational efforts - often in collaboration with experimental groups - to understand spectroscopic and chemical properties of ionic liquids (ILs). Molecular dynamics, including their inhomogeneous character, responsible for key spectral features observed in dielectric absorption, infra-red (IR) and fluorescence correlation spectroscopy (FCS) measurements are elucidated. Mechanisms of chemical processes involving imidazolium-based ILs are illustrated for CO2 capture and related reactions, transesterification of cellulose, and Au nanocluster-catalyzed Suzuki cross-coupling reaction with attention paid to differing roles of IL ions. A comparison with experiments is also made.

Reducing low-value ED coags across 11 hospitals in a safety net setting.

BACKGROUND: Prothrombin/international normalized ratio and activated partial thromboplastin time (PT/INR and aPTT) are frequently ordered in emergency departments (EDs), but rarely affect management. They offer limited utility outside of select indications. Several quality improvement initiatives have shown reduction in ED use of PT/INR and aPTT using multifaceted interventions in well-resourced settings. Successful reduction of these low-value tests has not yet been shown using a single intervention across a large hospital system in a safety net setting. This study aims to determine if an intervention of two BPAs is associated with a reduction in PT/INR and aPTT usage across a large safety net system. METHODS: This initiative was set at a large safety net system in the United States with 11 acute care hospitals. Two Best Practice Advisories (BPAs) discouraging inappropriate PT/INR and aPTT use were implemented from March 16, 2022-August 30, 2022. Order rate per 100 ED patients during the pre-intervention period was compared to the post-intervention period on both the system and individual hospital level. Complete blood count (CBC) testing served as a control, and packed red blood cell transfusions served as a balancing measure. An interrupted time series regression analysis was performed to capture immediate and temporal changes in ordering for all tests in the pre and post-intervention periods. RESULTS: PT/INR tests exhibited an absolute decline of 4.11 tests per 100 ED encounters (95% confidence interval -5.17 to -3.05; relative reduction of 18.9%). aPTT tests exhibited absolute decline of 4.03 tests per 100 ED encounters (95% CI -5.10 to -2.97; relative reduction of 19.8%). The control measure, CBC, did not significantly change (-0.43, 95% CI -2.83 to 1.96). Individual hospitals showed variable response, with absolute reductions from 2.02 to 9.6 tests per 100 ED encounters for PT/INR (relative reduction 12.1%-30.5%) and 2.07 to 10.04 for aPTT (relative reduction 12.1%-31.4%). Regression analysis showed that the intervention caused an immediate 25.7% decline in PT/INR and 24.7% decline in aPTT tests compared to the control measure. The slope differences (rate of order increase pre vs post intervention) did not significantly decline compared to the control. CONCLUSIONS: This BPA intervention reduced PT/INR and aPTT use across 11 EDs in a large, urban, safety net system. Further study is needed in implementation to other non-safety net settings.

Reducing daily dosing in opioid prescriptions in 11 safety net emergency departments.

BACKGROUND: The United States continues to face a significant issue with opioid misuse, overprescribing, dependency, and overdose. Electronic health record (EHR) interventions have shown to be an effective tool to modify opioid prescribing behaviors. This quality improvement project describes an EHR intervention to reduce daily dosing in opioid prescriptions in 11 emergency departments (ED) across the largest safety net health system in the US. MEASURES: The primary outcome measure was the rates of oxycodone-acetaminophen 5-325 mg prescriptions exceeding 50 morphine milligram equivalents per day (MMED) pre- vs. post-intervention; and stratified by individual hospitals and provider type. INTERVENTION: The defaults for dose and frequency were uniformly changed to 'every 6 hours as needed' and '1 tablet', respectively, across 11 EDs. OUTCOMES: The percentage of prescriptions greater than or equal to 50 MMED decreased from 46.0% (1624 of 3530 prescriptions) to 1.6% (52 of 3165 prescriptions) (96.4% relative reduction; p < 0.001). All 11 hospitals had a significant reduction in prescriptions exceeding 50 MMED. Nurse practitioners had the highest relative reduction of prescriptions exceeding 50 MMED at 100% (p < 0.001), and the attendings/fellows had the lowest relative reduction at 95.6% (p < 0.001). CONCLUSIONS/LESSONS LEARNED: Default nudges are a simple yet powerful intervention that can strongly influence opioid prescribing patterns.

Structural Characterization of Cytochrome c'ß-Met from an Ammonia-Oxidizing Bacterium.

The ammonia-oxidizing bacterium Nitrosomonas europaea expresses two cytochromes in the P460 superfamily that are predicted to be structurally similar. In one, cytochrome (cyt) P460, the substrate hydroxylamine (NH2OH) is converted to nitric oxide (NO) and nitrous oxide (N2O) requiring a unique heme-lysyl cross-link in the catalytic cofactor. In the second, cyt c'ß-Met, the cross-link is absent, and the cytochrome instead binds H2O2 forming a ferryl species similar to compound II of peroxidases. Here, we report the 1.80 Å crystal structure of cyt c'ß-Met─a well-expressed protein in N. europaea with a lysine to a methionine replacement at the cross-linking position. The structure of cyt c'ß-Met is characterized by a large ß-sheet typical of P460 members; however, several localized structural differences render cyt c'ß-Met distinct. This includes a large lasso-like loop at the "top" of the cytochrome that is not observed in other structurally characterized members. Active site variation is also observed, especially in comparison to its closest homologue cyt c'ß from the methane-oxidizing Methylococcus capsulatus Bath, which also lacks the cross-link. The phenylalanine "cap" which is presumed to control small ligand access to the distal heme iron is replaced with an arginine, reminiscent of the strictly conserved distal arginine in peroxidases and to the NH2OH-oxidizing cytochromes P460. A critical proton-transferring glutamate residue required for NH2OH oxidation is nevertheless missing in the active site. This in part explains the inability of cyt c'ß-Met to oxidize NH2OH. Our structure also rationalizes the absence of a methionyl cross-link, although the side chain's spatial position in the structure does not eliminate the possibility that it could form under certain conditions.

Pim-2 regulates bone resorptive activity of osteoclasts via V-ATPase a3 isoform expression in periodontal disease.

Cytoplasmic serine/threonine Pim kinases have emerged as important modulators of immune regulation and oncology. However, their regulatory roles in bone remodeling remain obscure. Here, we aimed to determine the roles of Pim kinases in periodontal disease (PD), focusing on the regulation of osteoclastogenesis and bone resorptive activity. We investigated Pim kinases expression in PD by analyzing data from the online Gene Expression Omnibus database and using ligature-induced periodontitis mouse model. The expression of Pim kinases during receptor activator of nuclear factor kB ligand (RANKL)-induced osteoclastogenesis was assessed in mouse bone marrow-derived macrophages (BMMs) using reverse transcription polymerase chain reaction. Osteoclast differentiation and bone resorption activity were respectively verified by tartrate-resistant acid phosphatase staining and dentin disc-based bone resorption assays. We silenced and overexpressed Pim-2 using small interfering RNA (siRNA) and retroviral vector, respectively, to investigate the molecular mechanisms underlying Pim-2 regulation in RANKL-induced osteoclastogenesis and bone resorption activity. Upregulated expression of Pim-2 was observed in both patients with PD and periodontitis-affected mouse gingival tissues. siRNA-mediated silencing of Pim-2 in BMMs diminished RANKL-induced resorptive activity without affecting osteoclastogenesis. Moreover, RANKL-triggered stimulation of a3 isoform, which is a subunit of vacuolar-type ATPase, was selectively attenuated in BMMs on silencing Pim-2. The overexpression of Pim-2 with a retroviral vector stimulated the a3 subunit, thus inducing bone resorption activity. Taken together, these results suggest that Pim-2 acts as a major modulator of osteoclastic activity by regulating a3 isoform expression in PD.

Choosing Wisely in Adult Hospital Medicine: Co-creation of New Recommendations for Improved Healthcare Value by Clinicians and Patient Advocates.

BACKGROUND: The American Board of Internal Medicine Foundation's Choosing Wisely campaign has resulted in a vast number of recommendations to reduce low-value care. Implementation of these recommendations, in conjunction with patient input, remains challenging. OBJECTIVE: To create updated Society of Hospital Medicine Adult Hospitalist Choosing Wisely recommendations that incorporate patient input from inception. DESIGN AND PARTICIPANTS: This was a multi-phase study conducted by the Society of Hospital Medicine's High Value Care Committee from July 2017 to January 2020 involving clinicians and patient advocates. APPROACH: Phase 1 involved gathering low-value care recommendations from patients and clinicians across the USA. Recommendations were reviewed by the committee in phase 2. Phase 3 involved a modified Delphi scoring in which 7 committee members and 7 patient advocates voted on recommendations based on strength of evidence, potential for patient harm, and relevance to either hospital medicine or patients. A patient-friendly script was developed to allow advocates to better understand the clinical recommendations. KEY RESULTS: A total of 1265 recommendations were submitted by clinicians and patients. After accounting for similar suggestions, 283 recommendations were categorized. Recommendations with more than 10 mentions were advanced to phase 3, leaving 22 recommendations for the committee and patient advocates to vote upon. Utilizing a 1-5 Likert scale, the top combined recommendations were reducing use of opioids (4.57), improving sleep (4.52), minimizing overuse of oxygen (4.52), reducing CK-MB use (4.50), appropriate venous thromboembolism prophylaxis (4.43), and decreasing daily chest x-rays (4.43). CONCLUSIONS: Specific voting categories, along with the use of patient-friendly language, allowed for the successful co-creation of recommendations.

Addressing Barriers to Reducing Prescribing and Implementing Deprescribing of Sedative-Hypnotics in Primary Care.

OBJECTIVE: To describe interventions that target patient, provider, and system barriers to sedative-hypnotic (SH) deprescribing in the community and suggest strategies for healthcare teams. DATA SOURCES: Ovid MEDLINE ALL and EMBASE Classic + EMBASE (March 10, 2021). STUDY SELECTION AND DATA EXTRACTION: English-language studies in primary care settings. DATA SYNTHESIS: 20 studies were themed as patient-related and prescriber inertia, physician skills and awareness, and health system constraints. Patient education strategies reduced SH dose for 10% to 62% of participants, leading to discontinuation in 13% to 80% of participants. Policy interventions reduced targeted medication use by 10% to 50%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patient engagement and empowerment successfully convince patients to deprescribe chronic SHs. Quality improvement strategies should also consider interventions directed at prescribers, including education and training, drug utilization reviews, or computer alerts indicating a potentially inappropriate prescription by medication, age, dose, or disease. Educational interventions were effective when they facilitated patient engagement and provided information on the harms and limited evidence supporting chronic use as well as the effectiveness of alternatives. Decision support tools were less effective than prescriber education with patient engagement, although they can be readily incorporated in the workflow through prescribing software. CONCLUSIONS: Several strategies with demonstrated efficacy in reducing SH use in community practice were identified. Education regarding SH risks, how to taper, and potential alternatives are essential details to provide to clinicians, patients, and families. The strategies presented can guide community healthcare teams toward reducing the community burden of SH use.

Photoprotective effects of sphingomyelin-containing milk phospholipids in ultraviolet B-irradiated hairless mice by suppressing nuclear factor-κB expression.

Ceramide-containing phospholipids improve skin hydration and barrier function and are ideal for use in skin care products. In this study, we evaluated the photoprotective effect of milk phospholipids on the skin condition of UVB-irradiated hairless mice. Skin parameters were assessed following oral administration of milk phospholipids. The UVB irradiation induced photoaging in mice. The animals were divided into 5 groups: a control group (oral administration of saline with no UBV irradiation), UVB group (oral administration of saline with UVB irradiation), and 3 UVB irradiation groups receiving the milk phospholipids at 3 different concentrations of oral administration, 50 mg/kg (ML group), 100 mg/kg (MM group), and 150 mg/kg (MH group), for 8 wk. An increase in skin hydration and transepidermal water loss were improved in the 150 mg/kg of milk phospholipid-administered group. Hematoxylin and eosin staining revealed a decrease in epidermal thickness in the milk phospholipid-administered groups (50, 100, and 150 mg/kg of body weight). In particular, the 100 and 150 mg/kg groups showed significant changes in the area, length, and depth of the wrinkles compared with the UVB group. Moreover, the gene expression of matrix metalloproteins was attenuated, and that of proinflammatory cytokines, especially tumor necrosis factor-α, was significantly reduced in the milk phospholipid-administered groups than in the UVB group. The reduced ceramide and increased sphingosine-1-phosphate levels in the skin tissue due to UVB exposure were restored to levels similar to those of the control group following milk phospholipid administration. These results were confirmed to be due to the downregulation of protein expression of nuclear factor kappa-B (NF-κB) and phosphorylated IκB-α (inhibitor of κB α). Collectively, oral administration of milk phospholipids improves skin health through a synergistic effect on photoprotective activity.

Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy.

BACKGROUND AND AIMS: COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. METHODS: Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. RESULTS: Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p <0.0001). On liver histology, patients with COVID-19 and elevated ALT had significantly increased vWF and platelet staining, supporting a link between liver injury, coagulopathy, and endotheliopathy. Intralobular neutrophils positively correlated with platelet (p <0.0001) and vWF (p <0.01) staining, and IL-6 levels positively correlated with vWF staining (p <0.01). IL-6 trans-signaling leads to increased expression of procoagulant (factor VIII, vWF) and proinflammatory factors, increased cell surface vWF (p <0.01), and increased platelet attachment in LSECs. These effects were blocked by soluble glycoprotein 130 (IL-6 trans-signaling inhibitor), the JAK inhibitor ruxolitinib, and STAT1/3 small-interfering RNA knockdown. Hepatocyte fibrinogen expression was increased by the supernatant of LSECs subjected to IL-6 trans-signaling. CONCLUSION: IL-6 trans-signaling drives the coagulopathy and hepatic endotheliopathy associated with COVID-19 and could be a possible mechanism behind liver injury in these patients. LAY SUMMARY: Patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6) and its circulating receptor, which form a complex to induce inflammatory signals, have been observed in patients with COVID-19. This paper demonstrates that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.

SARS-CoV-2 show no infectivity at later stages in a prolonged COVID-19 patient despite positivity in RNA testing.

Inpatient coronavirus disease 2019 (COVID-19) cases present enormous costs to patients and health systems in the United States. Many hospitalized patients may continue testing COVID-19 positive even after the resolution of symptoms. Thus, a pressing concern for clinicians is the safety of discharging these asymptomatic patients if they have any remaining infectivity. This case report explores the viral viability in a patient with persistent COVID-19 over the course of a 2-month hospitalization. Positive nasopharyngeal swab samples were collected and isolated in the laboratory and analyzed by quantitative reverse-transcription polymerase chain reactions (qRT-PCR), and serology was tested for neutralizing antibodies throughout the hospitalization period. The patient experienced waning symptoms by hospital day 40 and had no viable virus growth by hospital day 41, suggesting no risk of infectivity, despite positive RT-PCR results which prolonged his hospital stay. Notably, this case showed infectivity for at least 24 days after disease onset, which is longer than the discontinuation of transmission-based precautions recommended by the Center for Disease Control and Prevention. Thus, our findings suggest that the timeline for discontinuing transmission-based precautions may need to be extended for patients with severe and prolonged COVID-19 disease. Additional large-scale studies are needed to draw definitive conclusions on the appropriate clinical management for these patients. ​.

To Expand the Evidence Base About Harms from Tests and Treatments.

Rigorous evidence about the broad range of harms that might be experienced by a patient in the course of testing and treatment is sparse. We aimed to generate recommendations for how researchers might more comprehensively evaluate potential harms of healthcare interventions, to allow clinicians and patients to better include this evidence in clinical decision-making. We propose seven domains of harms of tests and treatments that are relevant to patients: (1) physical impairment, (2) psychological distress, (3) social disruption, (4) disruption in connection to healthcare, (5) labeling, (6) financial impact, and (7) treatment burden. These domains will include a range of severity of harms and variation in timing after testing or treatment, attributable to the service itself or a resulting care cascade. Although some new measures may be needed, diverse data and tools are available to allow the assessment of harms comprehensively across these domains. We encourage researchers to evaluate harms in sub-populations, since the harms experienced may differ importantly by demographics, social determinants, presence of comorbid illness, psychological state, and other characteristics. Regulators, funders, and editors might require either assessment or reporting of harms in each domain or require justification for inclusion and exclusion of different domains.

Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

Chronic Thromboembolic Pulmonary Hypertension: the Bedside.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH), included in group 4 PH, is an uncommon complication of acute pulmonary embolism (PE), in which emboli in the pulmonary vasculature do not resolve but rather form into an organized scar-like obstruction which can result in right ventricular (RV) failure. Here we provide an overview of current diagnosis and management of CTEPH. RECENT FINDINGS: CTEPH management is complex with treatments that range from surgery, percutaneous interventions, to medical therapies. Current CTEPH medical therapies have largely been repurposed from pulmonary arterial hypertension (PAH). The diagnosis of CTEPH can be challenging, requiring a multimodality approach to differentiate from disease mimics. While these treatments improve symptoms, they may not reverse the underlying pathology of CTEPH.

Chronic Thromboembolic Pulmonary Hypertension: the Bench.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary embolism (PE), in which the red, platelet-rich thrombus does not resolve but forms into an organized yellow, fibrotic scar-like obstruction in the pulmonary vasculature. Here we review the pathobiology of CTEPH. RECENT FINDINGS: Our current knowledge has predominantly been informed by studies of human samples and animal models that are inherently limited in their ability to recapitulate all aspects of the disease. These studies have identified alterations in platelet biology and inflammation in the formation of a scar-like thrombus that comprised endothelial cells, myofibroblasts, and immune cells, along with a small vessel pulmonary arterial hypertension-like vasculopathy. The development of CTEPH-specific therapies is currently hindered by a limited knowledge of its pathobiology. The development of new CTEPH medical therapies will require new insights into its pathobiology that bridge the gap from bench to bedside.