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Background: There is an evolving focus on interprofessional education (IPE) to promote teamwork and collaboration in health professions education. Studies in medical students have shown that exposure to IPE leads to perceived improvements in interprofessional communication, effective work in healthcare teams, and understanding of professional limitations. Most research focuses on IPE in undergraduate medical education; less is known about how this functions in graduate medical education., Objective: To develop and implement a lecture-based intensive care unit (ICU) educational curriculum, incorporating content delivery by interprofessional team members (IPMs), and to use a mixed methods approach to explore learner and IPM perceptions surrounding the benefits and opportunities with this model of education., Methods: A standardized curriculum of core topics in critical care medicine was designed and implemented as a recurring interactive lecture series over the course of a medical ICU rotation at an academic hospital. The lectures were delivered by pulmonary and critical care attendings or fellows and IPMs, including pharmacists, dietitians, advanced practice providers, and physical therapists. Internal medicine residents' perceptions of faculty engagement in teaching, involvement in interprofessional care teams, and educational value of the rotation were analyzed quantitatively before and after intervention. Semistructured focus groups with residents and IPMs were held after implementation to explore the experience, motivations, and effectiveness of IPMs as educators. Themes were identified using a deductive approach, with coding by multiple team members., Results: Before lecture series implementation, 57 residents completed end-of-rotation evaluations. The average score for perceived faculty engagement and interest in teaching was 4.16 out of 5 (standard deviation [SD], 1.05). Forty-five residents completed evaluations after implementation, and the perception of faculty interest in teaching was not statistically different at 4.20 (SD, 0.92; P  = 0.98). Qualitative themes emerging from the focus groups included investment, shared goals and motivation for teaching, specialized knowledge and mutual respect, improving patient care, engagement and environment, downsides, and, finally, prioritization., Conclusion: Teaching by IPMs can be integrated into a lecture-based curriculum in an academic ICU. After implementation, residents identified that engagement of IPMs as teachers may lead to improved understanding of roles and responsibilities and mutual respect. IPMs cite sharing of specialized knowledge and return on investment as motivations for teaching., (Copyright © 2024 by the American Thoracic Society.)

Vasopressor medications for circulatory shock have historically been administered through central venous catheters due to concern for extravasation injury when given peripherally. However, recent studies have demonstrated the safety of peripheral administration of vasopressor medications at lower doses and for a limited duration. Peripheral use of vasopressors is appealing to both patients and providers, as obtaining central access is an invasive procedure associated with the risk of pneumothorax, bleeding, and infection. Furthermore, waiting to initiate these medications until central access is obtained can lead to delays in care. Conversely, valid concerns remain regarding the risk of tissue extravasation associated with peripheral vasopressors, which can be life and limb threatening. We discuss the guidelines and data for optimal dose, duration, intravenous line (IV) size, IV location, and nursing IV site monitoring for peripheral vasopressors. We then explore adverse events associated with peripheral vasopressors. Finally, we describe how this practice change may impact hospital medicine providers.

We sought to identify factors affecting physicians' cognition and clinical behavior when evaluating patients that may need fluid therapy., Background: Proponents of dynamic fluid responsiveness testing advocate measuring cardiac output or stroke volume after a maneuver to prove that further fluids will increase cardiac output. However, surveys suggest that fluid therapy in clinical practice is often given without prior responsiveness testing., Design: Thematic analysis of face-to-face structured interviews., Setting: ICUs and medical-surgical wards in acute care hospitals., Subjects: Intensivists and hospitalist physicians., Interventions: None., Measurements and Main Results: We conducted 43 interviews with experienced physicians in 19 hospitals. Hospitalized patients with hypotension, tachycardia, oliguria, or elevated serum lactate are commonly seen by physicians who weigh the risks and benefits of more fluid therapy. Encounters are often with unfamiliar patients and evaluation and decisions are completed quickly without involving other physicians. Dynamic testing for fluid responsiveness is used much less often than static methods and fluid boluses are often ordered with no testing at all. This approach is rationalized by factors that discourage dynamic testing: unavailability of equipment, time to obtain test results, or lack of expertise in obtaining valid data. Two mental calculations are particularly influential: physicians' estimate of the base rate of fluid responsiveness (determined by physical examination, chart review, and previous responses to fluid boluses) and physicians' perception of patient harm if 500 or 1,000 mL fluid boluses are ordered. When the perception of harm is low, physicians use heuristics that rationalize skipping dynamic testing., Limitations: Geographic limitation to hospitals in Minnesota, United States., Conclusions: If dynamic responsiveness testing is to be used more often in routine clinical practice, physicians must be more convinced of the benefits of dynamic testing, that they can obtain valid results quickly and believe that even small fluid boluses harm their patients., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background. Variability in outpatient specialty clinic schedules contributes to numerous adverse effects including chaotic clinic settings, provider burnout, increased patient waiting times, and inefficient use of resources. This research measures the benefit of balancing provider schedules in an outpatient specialty clinic. Design. We developed a constrained optimization model to minimize the variability in provider schedules in an outpatient specialty clinic. Schedule variability was defined as the variance in the number of providers scheduled for clinic during each hour the clinic is open. We compared the variance in the number of providers scheduled per hour resulting from the constrained optimization schedule with the actual schedule for three reference scenarios used in practice at M Health Fairview's Clinics and Surgery Center as a case study. Results. Compared to the actual schedules, use of constrained optimization modeling reduced the variance in the number of providers scheduled per hour by 92% (1.70-0.14), 88% (1.98-0.24), and 94% (1.98-0.12). When compared with the reference scenarios, the total, and per provider, assigned clinic hours remained the same. Use of constrained optimization modeling also reduced the maximum number of providers scheduled during each of the actual schedules for each of the reference scenarios. The constrained optimization schedules utilized 100% of the available clinic time compared to the reference scenario schedules where providers were scheduled during 87%, 92%, and 82% of the open clinic time, respectively. Limitations. The scheduling model's use requires a centralized provider scheduling process in the clinic. Conclusions. Constrained optimization can help balance provider schedules in outpatient specialty clinics, thereby reducing the risk of negative effects associated with highly variable clinic settings., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Current management of childhood leukemia is tailored based on disease risk determined by clinical features at presentation. Whether properties of the host immune response impact disease risk and outcome is not known. Here, we combine mass cytometry, single cell genomics, and functional studies to characterize the BM immune environment in children with B cell acute lymphoblastic leukemia and acute myelogenous leukemia at presentation. T cells in leukemia marrow demonstrate evidence of chronic immune activation and exhaustion/dysfunction, with attrition of naive T cells and TCF1+ stem-like memory T cells and accumulation of terminally differentiated effector T cells. Marrow-infiltrating NK cells also exhibit evidence of dysfunction, particularly in myeloid leukemia. Properties of immune cells identified distinct immune phenotype-based clusters correlating with disease risk in acute lymphoblastic leukemia. High-risk immune signatures were associated with expression of stem-like genes on tumor cells. These data provide a comprehensive assessment of the immune landscape of childhood leukemias and identify targets potentially amenable to therapeutic intervention. These studies also suggest that properties of the host response with depletion of naive T cells and accumulation of terminal-effector T cells may contribute to the biologic basis of disease risk. Properties of immune microenvironment identified here may also impact optimal application of immune therapies, including T cell-redirection approaches in childhood leukemia.

BACKGROUNDPD-1 and PD-L1 have been studied interchangeably in the clinic as checkpoints to reinvigorate T cells in diverse tumor types. Data for biologic effects of checkpoint blockade in human premalignancy are limited.METHODSWe analyzed the immunologic effects of PD-L1 blockade in a clinical trial of atezolizumab in patients with asymptomatic multiple myeloma (AMM), a precursor to clinical malignancy. Genomic signatures of PD-L1 blockade in purified monocytes and T cells in vivo were also compared with those following PD-1 blockade in lung cancer patients. Effects of PD-L1 blockade on monocyte-derived DCs were analyzed to better understand its effects on myeloid antigen-presenting cells.RESULTSIn contrast to anti-PD-1 therapy, anti-PD-L1 therapy led to a distinct inflammatory signature in CD14+ monocytes and increase in myeloid-derived cytokines (e.g., IL-18) in vivo. Treatment of AMM patients with atezolizumab led to rapid activation and expansion of circulating myeloid cells, which persisted in the BM. Blockade of PD-L1 on purified monocyte-derived DCs led to rapid inflammasome activation and synergized with CD40L-driven DC maturation, leading to greater antigen-specific T cell expansion.CONCLUSIONThese data show that PD-L1 blockade leads to distinct systemic immunologic effects compared with PD-1 blockade in vivo in humans, particularly manifest as rapid myeloid activation. These findings also suggest an additional role for PD-L1 as a checkpoint for regulating inflammatory phenotype of myeloid cells and antigen presentation in DCs, which may be harnessed to improve PD-L1-based combination therapies.TRIAL REGISTRATIONNCT02784483.FUNDINGThis work is supported, in part, by funds from NIH/NCI (NCI CA197603, CA238471, and CA208328).

There is widespread concern regarding the high price of innovative medicines and their impact on the sustainability of healthcare systems. However, the debate rarely accounts for the evolution of prices over the lifetime of the medicine and the impact of competitive forces. This article uses the experience of hepatitis C (HCV), during the years 2010-2017 to examine the impact of in-class competition and implications for policies that enable competition. To study the HCV market, we focused on European countries and applied a two-step approach involving a comprehensive literature review and an analysis of monthly sales data in US$ across seven European countries from July 2011 until July 2017. We find that competition to address the unmet medical need has led to significant treatment improvements to the benefit of patients, payers and the wider healthcare system and society. Competitive launches have led to innovative agreements, lowering the cost per treatment and improving patient access to treatment. For innovators, intense competition does not only impact the price set and their market share but in many cases shortens the economic life of the product to only a fraction of the patented period. This has an impact on future research decisions, focusing efforts on areas where unmet need is greatest. Sustainable innovation requires a well-balanced policy framework that provides the appropriate incentives and encourages competition., (Copyright © 2019. Published by Elsevier B.V.)

Preneoplastic lesions carry many of the antigenic targets found in cancer cells but often exhibit prolonged dormancy. Understanding how the host response to premalignancy is maintained and altered during malignant transformation is needed to prevent cancer. In order to understand the immune microenvironment in precursor monoclonal gammopathy of undetermined significance (MGUS) and myeloma, we analyzed bone marrow immune cells from 12 healthy donors and 26 MGUS/myeloma patients by mass cytometry and concurrently profiled transcriptomes of 42,606 single immune cells from these bone marrows. Compared to age-matched healthy donors, memory T cells from both MGUS and myeloma patients exhibit greater terminal-effector differentiation. However, memory T cells in MGUS show greater enrichment of stem-like TCF1/7hi cells. Clusters of T cells with stem-like and tissue-residence genes were also found to be enriched in MGUS by single-cell transcriptome analysis. Early changes in both NK and myeloid cells were also observed in MGUS. Enrichment of stem-like T cells correlated with a distinct genomic profile of myeloid cells and levels of Dickkopf-1 in bone-marrow plasma. These data describe the landscape of changes in both innate and adaptive immunity in premalignancy and suggest that attrition of the bone-marrow-resident T cell compartment due to loss of stem-like cells may underlie loss of immune surveillance in myeloma.

[This corrects the article DOI: 10.18632/oncotarget.1108.].

Background: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA)., Methods and Findings: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression., Conclusions: These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations., Competing Interests: The authors have declared that no competing interests exist.