How Should Focus Be Shifted From Individual Preference to Collective Wisdom for Patients at the End of Life With Antimicrobial-Resistant Infections?

Despite growth in numbers of organizational antimicrobial stewardship programs, antimicrobial resistance continues to escalate. Interprofessional education and collaboration are needed to make these programs appropriately responsive to the ethically and clinically complex needs of patients at the end of life whose care plans still require antimicrobial management.

Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (range, 0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% confidence interval, 78-87) at age 15 years and 70% (61-80) at 30 years. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hot spot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared with 71% (62-81) and 48% (34-68) in patients with any other variant (class II; P < .0001). The cumulative incidence rates of disease-related complications such as severe bleeding (P = .007), life-threatening infection (P < .0001), and autoimmunity (P = .004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (P = .6) was not different between classes I and II. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of the variant is a biomarker to predict the outcome for patients with WAS.

Embedding Nursing Ethics Within Teaching Strategies in Nurse Residency Programs.

Exposing new nurses to theoretical teaching strategies that help them to navigate the ethical challenges in clinical practice is essential for retention and long-term job satisfaction. This article explores the rationale for teaching ethics content in nurse residency programs and ways to navigate ethical decision-making in the clinical setting. Examples of evidence-informed teaching strategies that enhance knowledge retention and reduce the gap between ethical theory and practice are included.

ERBB3 Overexpression is Enriched in Diverse Patient Populations with Castration-sensitive Prostate Cancer and is Associated with a Unique AR Activity Signature.

PURPOSE: Despite successful clinical management of castration-sensitive prostate cancer (CSPC), the 5-year survival rate for men with castration-resistant prostate cancer is only 32%. Combination treatment strategies to prevent disease recurrence are increasing, albeit in biomarker-unselected patients. Identifying a biomarker in CSPC to stratify patients who will progress on standard-of-care therapy could guide therapeutic strategies. EXPERIMENTAL DESIGN: Targeted deep sequencing was performed for the University of Illinois (UI) cohort (n = 30), and immunostaining was performed on a patient tissue microarray (n = 149). Bioinformatic analyses identified pathways associated with biomarker overexpression (OE) in the UI cohort, consolidated RNA sequencing samples accessed from Database of Genotypes and Phenotypes (n = 664), and GSE209954 (n = 68). Neutralizing antibody patritumab and ectopic HER3 OE were utilized for functional mechanistic experiments. RESULTS: We identified ERBB3 OE in diverse patient populations with CSPC, where it was associated with advanced disease at diagnosis. Bioinformatic analyses showed a positive correlation between ERBB3 expression and the androgen response pathway despite low dihydrotestosterone and stable expression of androgen receptor (AR) transcript in Black/African American men. At the protein level, HER3 expression was negatively correlated with intraprostatic androgen in Black/African American men. Mechanistically, HER3 promoted enzalutamide resistance in prostate cancer cell line models and HER3-targeted therapy resensitized therapy-resistant prostate cancer cell lines to enzalutamide. CONCLUSIONS: In diverse patient populations with CSPC, ERBB3 OE was associated with high AR signaling despite low intraprostatic androgen. Mechanistic studies demonstrated a direct link between HER3 and enzalutamide resistance. ERBB3 OE as a biomarker could thus stratify patients for intensification of therapy in castration-sensitive disease, including targeting HER3 directly to improve sensitivity to AR-targeted therapies.

Operationalizing the role of the nurse ethicist: More than a job.

The idea of a role in nursing that includes expertise in ethics has been around for more than 30 years. Whether or not one subscribes to the idea that nursing ethics is separate and distinct from bioethics, nursing practice has much to contribute to the ethical practice of healthcare, and with the strong grounding in ethics and aspiration for social justice considerations in nursing, there is no wonder that the specific role of the nurse ethicist has emerged. Nurse ethicists, expert in nursing practice and the application of ethical theories and concepts, are well positioned to guide nurses through complex ethical challenges. However, there is limited discussion within the field regarding the specific job responsibilities that the nurse ethicist ought to have. The recent appearance of job postings with the title "nurse ethicist" suggest that some healthcare institutions have identified the value of a nurse in the practice of ethics and are actively recruiting. Discomfort about the possibility of others defining the role of the nurse ethicist inspired this paper (and special issue). If the nurse ethicist is to be seen as an integral part of addressing ethical dilemmas and ethical conflicts that arise in healthcare, then nurse ethicists ought to be at the forefront of defining this role. In this paper, we draw upon our own experiences as nurse ethicists in large academic healthcare systems to describe the essential elements that ought to be addressed in a job description for a nurse ethicist practicing in a clinical setting linked to academic programs. Drawing upon our experience and the literature, we describe how we perceive the nurse ethicist adds value to healthcare organizations and teams of professional ethicists.

Recommendations for the management of acute immune thrombocytopenia in children. A Consensus Conference from the Italian Association of Pediatric Hematology and Oncology.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired immune-mediated bleeding disorder characterized by isolated thrombocytopenia. Its estimated yearly incidence in the pediatric population is 1.9-6.4/100,000. ITP in children is usually a self-limiting and benign disorder. The clinical management of children with ITP often remains controversial, as robust randomized trials on the management of this disorder are lacking. Treatments vary widely in clinical practice and existing guidelines from hematology societies on clinical management offer indications based largely on expert opinion rather than strong evidence. MATERIALS AND METHODS: The Coagulative Disorder Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) developed this document to collect shared expert opinions on the management of newly diagnosed ITP, updating previous guidelines and providing recommendations to pediatricians. Each statement has been given a score expressing the strength of evidence, appropriateness and agreement among participants. RESULTS: Clear-cut definitions of the clinical phases of the disease and clinical response are stated. Recommendations are given regarding the classification of bleeding symptoms, evaluation of bleeding risk, diagnosis, and prognostic factors. Specific recommendations for treatment include indications for first-line (intravenous immunoglobulins, steroids) and second-line (combined therapy, thrombopoietin receptor agonists, immunosuppressive drugs, rituximab) therapeutic agents, as well as hemorrhagic emergency and supportive treatment, including emergency splenectomy. The optimal follow-up schedule, the relation between ITP and vaccines and health-related quality-of-life issues are also discussed. DISCUSSION: The panel achieved broad consensus on issues related to how to treat children with newly diagnosed ITP, providing a comprehensive review of all relevant clinical aspects.

Trends and Predictors of Glycemic Control Among Adults With Type 2 Diabetes Covered by Alabama Medicaid, 2011-2019.

INTRODUCTION: Despite advances in diabetes management, only one-quarter of people with diabetes in the US achieve optimal targets for glycated hemoglobin A1c (HbA1c), blood pressure, and cholesterol. We sought to evaluate temporal trends and predictors of achieving glycemic control among adults with type 2 diabetes covered by Alabama Medicaid from 2011 through 2019. METHODS: We completed a retrospective analysis of Medicaid claims and laboratory data, using person-years as the unit of analysis. Inclusion criteria were being aged 19 to 64 years, having a diabetes diagnosis, being continuously enrolled in Medicaid for a calendar year and preceding 12 months, and having at least 1 HbA1c result during the study year. Primary outcomes were HbA1c thresholds of <7% and <8%. Primary exposure was study year. We conducted separate multivariable-adjusted logistic regressions to evaluate relationships between study year and HbA1c thresholds. RESULTS: We included 43,997 person-year observations. Mean (SD) age was 51.0 (9.9) years; 69.4% were women; 48.1% were Black, 42.9% White, and 0.4% Hispanic. Overall, 49.1% had an HbA1c level of <7% and 64.6% <8%. Later study years and poverty-based eligibility were associated with lower probability of reaching target HbA1c levels of <7% or <8%. Sex, race, ethnicity, and geography were not associated with likelihood of reaching HbA1c <7% or <8% in any model. CONCLUSION: Later study years were associated with lower likelihood of meeting target HbA1c levels compared with 2011, after adjusting for covariates. With approximately 35% not meeting an HbA1c target of <8%, more work is needed to improve outcomes of low-income adults with type 2 diabetes.

African Mountain Thistles: Three New Genera in the Carduus-Cirsium Group.

The floras on the highest mountains in tropical eastern Africa are among the most unique floras in the world. Despite the exceptionally high concentration of endemic species, these floras remain understudied from an evolutionary point of view. In this study, we focus on the Carduus-Cirsium group (subtribe Carduinae) to unravel the evolutionary relationships of the species endemic to the tropical Afromontane and Afroalpine floras, aiming to improve the systematics of the group. We applied the Hyb-Seq approach using the Compositae1061 probe set on 190 samples (159 species), encompassing representatives of all genera of Carduinae. We used two recently developed pipelines that enabled the processing of raw sequence reads, identification of paralogous sequences and segregation into orthologous alignments. After the implementation of a missing data filter, we retained sequences from 986 nuclear loci and 177 plastid regions. Phylogenomic analyses were conducted using both concatenated and summary-coalescence methods. The resulting phylogenies were highly resolved and revealed three distinct evolutionary lineages consisting of the African species traditionally referred to as Carduus and Cirsium. Consequently, we propose the three new genera Afrocarduus, Afrocirsium and Nuriaea; the latter did notably not belong to the Carduus-Cirsium group. We detected some incongruences between the phylogenies based on concatenation vs. coalescence and on nuclear vs. plastid datasets, likely attributable to incomplete lineage sorting and/or hybridization.

Distress and the Long-Stay Pediatric Intensive Care Unit Admission: A Longitudinal Study of Parents and the Medical Team.

Prolonged critical illness in children has emotional consequences for both parents and providers. In this observational cohort study, we longitudinally surveyed anxiety and depression in parents and moral distress in pediatric intensive care unit (PICU) providers (attendings, fellows, and bedside registered nurses) and explored their trajectories and relationships. Anxiety/depression and provider moral distress were measured using the Hospital Anxiety and Depression Scale and the Moral Distress Thermometer, respectively. The relationships of parental and provider distress were evaluated using Spearman's correlations, and their trajectories and potentially associated variables were explored using quadratic random slope and intercept models. Predetermined associated factors included demographic and clinical factors, including parent psychosocial risk and intubation status. We found parental anxiety and depression decreased over their child's admission, and parental psychosocial risk was significantly associated with anxiety (coefficient = 4.43, p < 0.001). Clinicians in different roles had different mean levels and trajectories of moral distress, with fellows reporting greater distress early in admissions and nurses later in admissions. Parental anxiety/depression and provider distress were significantly, though moderately, correlated. We conclude that anxiety and depression in parents of children with prolonged PICU admissions and the moral distress of their clinicians correlate and vary over time and by provider role.

Professional responsibility, nurses, and conscientious objection: A framework for ethical evaluation.

Conscientious objections (CO) can be disruptive in a variety of ways and may disadvantage patients and colleagues who must step-in to assume care. Nevertheless, nurses have a right and responsibility to object to participation in interventions that would seriously harm their sense of integrity. This is an ethical problem of balancing risks and responsibilities related to patient care. Here we explore the problem and propose a nonlinear framework for exploring the authenticity of a claim of CO from the perspective of the nurse and of those who must evaluate such claims. We synthesized the framework using Rest's Four Component Model of moral reasoning along with tenets of the International Council of Nursing's (ICN) Code of Ethics for Nurses and insights from relevant ethics and nursing ethics literature. The resulting framework facilitates evaluating potential consequences of a given CO for all involved. We propose that the framework can also serve as an aid for nurse educators as they prepare students for practice. Gaining clarity about the sense in which the concept of conscience provides a defensible foundation for objecting to legally, or otherwise ethically, permissible actions, in any given case is critical to arriving at an ethical and reasonable plan of action.

Evaluation of Interventions to Address Moral Distress: A Multi-method Approach.

Moral distress is a well-documented phenomenon for health care providers (HCPs). Exploring HCPs' perceptions of participation in moral distress interventions using qualitative and quantitative methods enhances understanding of intervention effectiveness. The purpose of this study was to measure and describe the impact of a two-phased intervention on participants' moral distress. Using a cross-over design, the project aimed to determine if the intervention would decrease moral distress, enhance moral agency, and improve perceptions about the work environment. We used quantitative instruments and explored participants' perceptions of the intervention using semi-structured interviews. Participants were from inpatient settings, within three major hospitals of a large, urban healthcare system in the Midwest, United States. Participants included nurses (80.6%) and other clinical care providers. Using generalized linear mixed modeling we assessed the change in each of the outcome variables over time controlling for groups. Interviews were audiotaped and professionally transcribed. The written narratives were coded into themes. The change in scores on study instruments trended in the desired direction however did not meet statistical significance. Qualitative interviews revealed that intervention effectiveness was derived from a combination of learning benefits, psychological benefits, and building community that promoted moral agency. Findings demonstrate a clear link between moral distress and moral agency and suggest that Facilitated Ethics Conversations can enhance the work environment. Findings provide insight for developing evidenced-based approaches to address moral distress of hospital nurses.

A Novel Web-Based and Mobile Application to Measure Real-Time Moral Distress: An Initial Pilot and Feasibility Study.

PROBLEM DEFINITION: Moral distress (MoD) is a vital clinical indicator linked to clinician burnout and provider concerns about declining patient care quality. Yet it is not routinely assessed. Earlier, real-time recognition may better target interventions aimed at alleviating MoD and thereby increase provider well-being and improve patient care quality. INITIAL APPROACH AND TESTING: Combining two validated MoD instruments (the Moral Distress Thermometer [MDT] and the Measure of Moral Distress for Healthcare Professionals [MMD-HP]), the authors developed a novel mobile and Web-based application environment to measure and report levels MoD and their associated causes. This app was tested for basic feasibility and acceptability in two groups: graduate nursing students and practicing critical care nurses. RESULTS: The MDT app appears feasible and acceptable for future use. All participants (n = 34) indicated the MDT app was satisfying to use, and 91.2% (n = 31) indicated the app was "very appropriate" for measuring MoD. In addition, 84.2% (n =16) of practicing nurses indicated the app fit either "somewhat well" (47.4%, n = 9) or "very well" (36.8%, n = 7) into their typical workday, and 68.4% (n = 13) said they were either "extremely likely" or "somewhat likely" to use the app daily in clinical practice. KEY INSIGHTS AND NEXT STEPS: Education about moral distress and its associated causes proved important to the MDT app's success. It is ready for future validity and reliability testing, as well as examining usability beyond nursing, longitudinal data monitoring, and possible leveraging to pre- and postintervention evaluation studies.

Moral Distress in the ICU: Measuring, Tracking, and Responding to Staff Experiences.

Until the surges of COVID-19 patients overwhelmed our health care system, moral distress was largely unknown outside of health care. We conducted a study in a 36-bed intensive care unit (ICU) over an 8-week period to determine the severity and contributing factors to clinicians' moral distress and how their moral distress impacted intent to leave, and to assess utilization of resources to mitigate the problem. This article describes the level of moral distress experienced by ICU staff, the disparity between hospital-provided resources and the contributing factors of moral distress, and the potential financial cost of job turnover due to moral distress.

Repeatedly Northwards and Upwards: Southern African Grasslands Fuel the Colonization of the African Sky Islands in Helichrysum (Compositae).

The Afromontane and Afroalpine areas constitute some of the main biodiversity hotspots of Africa. They are particularly rich in plant endemics, but the biogeographic origins and evolutionary processes leading to this outstanding diversity are poorly understood. We performed phylogenomic and biogeographic analyses of one of the most species-rich plant genera in these mountains, Helichrysum (Compositae-Gnaphalieae). Most previous studies have focused on Afroalpine elements of Eurasian origin, and the southern African origin of Helichrysum provides an interesting counterexample. We obtained a comprehensive nuclear dataset from 304 species (≈50% of the genus) using target-enrichment with the Compositae1061 probe set. Summary-coalescent and concatenation approaches combined with paralog recovery yielded congruent, well-resolved phylogenies. Ancestral range estimations revealed that Helichrysum originated in arid southern Africa, whereas the southern African grasslands were the source of most lineages that dispersed within and outside Africa. Colonization of the tropical Afromontane and Afroalpine areas occurred repeatedly throughout the Miocene-Pliocene. This timing coincides with mountain uplift and the onset of glacial cycles, which together may have facilitated both speciation and intermountain gene flow, contributing to the evolution of the Afroalpine flora.

Unmasking grief: Reflections on the complicated relationship between moral distress and grief.

Perinatal loss often occurs in the context of discovery of a medical condition that presents patients and healthcare providers (HCPs) with difficult choices. Treatment choices are influenced by medical technology, however inescapable prognostic uncertainty, coupled with shared decision-making can lead to ethical dilemmas (Graf et al., 2023) [1]. When patients experience perinatal loss HCPs must grapple with their own emotions. Their sense of grief arises from their empathic connection with patients, bearing witness to their grief. This grief may compound HCP moral distress. Moral distress has an element of emotion, however it is more than distress in tragic situations. Moral distress is linked to HCPs feeling responsible to take action (Dudzinski, 2016) [2]. In situations of perinatal loss, it is essential to acknowledge the grief and explore how it influences the experience of moral distress. This article will reflect on the impact of HCP grief in ethically complex situation of perinatal loss.

Improving Outpatient Follow-Up Rates for New In-Hospital Consults.

OBJECTIVE(S): This investigation aimed to define the rate of outpatient follow-up after in-hospital consultation, identify factors associated with establishing care, and evaluate an alternative scheduling process to improve outpatient adherence. METHODS: Two-phase, prospective study at an academic, tertiary-care institution from March 2020 to August 2022. First, all patients not previously known to our practice encountered via inpatient consult who warranted outpatient follow-up were prospectively captured. Logistic regression analysis was used to identify demographic, disease, and practice factors predictive of follow-up. Second, a randomized control trial was performed to validate the effects of pre-assigning appointments prior to discharge. RESULTS: Six hundred subjects were included in the final study cohort; 500 in phase-one, and 100 randomized during phase-two. In the phase-one cohort, 54% (n = 272) were lost to follow-up. Multivariate analysis showed increased odds of outpatient follow-up when appointments were pre-assigned before discharge (odds ratio [OR]: 3.69 [95% confidence interval [CI]: 2.29-5.96], p < 0.001), the primary reason for hospitalization was ENT and consult-related (OR: 3.29 [1.92-5.64], p < 0.001), and the diagnosis was one of Oncology (OR: 1.93 [1.02-3.69], p = 0.045) or Pediatrics (OR: 3.36 [1.41-7.98], p = 0.006) subspecialties. During phase-two, subjects randomized for pre-assigned appointments had higher outpatient follow-up (82%) compared to the control group (20%) (p < 0.001). CONCLUSION: Hospital-based consultations represent an important referral pathway for new patients. Disease characteristics may identify patients less likely to follow-up upon discharge. Appointment scheduling protocols, including pre-assigning appointments, are modifiable targets for improving adherence to care. Laryngoscope, 133:2540-2545, 2023.

Perceived discrimination in primary care: Does Payer mix matter?

INTRODUCTION: Previous literature has explored patient perceptions of discrimination by race and insurance status, but little is known about whether the payer mix of the primary care clinic (i.e., that is majority public insurance vs. majority private insurance clinics) influences patient perceptions of race- or insurance-based discrimination. METHODS: Between 2015-2017, we assessed patient satisfaction and perceived race- and insurance-based discrimination using a brief, anonymous post-clinic visit survey. RESULTS: Participants included 3,721 patients from seven primary care clinics-three public clinics and four private clinics. Results from unadjusted logistic regression models suggest higher overall reports of race- and insurance-based discrimination in public clinics compared with private clinics. In mulvariate analyses, increasing age, Black race, lower education and Medicaid insurance were associated with higher odds of reporting race- and insurance-based discrimination in both public and private settings. CONCLUSION: Reports of race and insurance discrimination are higher in public clinics than private clinics. Sociodemographic variables, such as age, Black race, education level, and type of insurance also influence reports of race- and insurance-based discrimination in primary care.