Considerations for specialized maternal-fetal care in the Somali-American community.

OBJECTIVE: This study describes the perceptions, personal and community experiences, and barriers to care of Somali-American families regarding specialized maternal-fetal care from their viewpoint. STUDY DESIGN: We conducted a semi-structured focus group study of Somali-American women (March 2023). We used qualitative analysis techniques to identify and report thematic findings. RESULTS: Fifty Somali-American women were interviewed in focus groups. Five themes were identified: 1) adherence to religious belief (namely Islamic) was paramount, including devotions of predestination (e.g. divine will) and permissibility of fetal intervention, 2) participants valued consensus among clinicians and were guided by prior experiences, 3) confidence in the medical team was important, and included the need to communicate effectively with clinicians and concerns regarding the accuracy of diagnosis, 4) decisional factors prioritized saving the life of the baby, and 5) treatment considerations included reluctance to intervene before birth. CONCLUSIONS: For the Somali-American participants, their faith identity was central when considering their medical needs, including a hesitance to treat a baby before birth due to Islamic belief in divine will. In addition, these community members highlighted the importance of trustworthy interpretation, cultural competence, clinician consensus, prior pregnancy experiences as well as experiences of other community members as having an impact on their trust in their medical care and diagnosis.

Beyond the consult question: Nurse ethicists as architects of moral spaces.

Nurse Ethicists bring a unique perspective to clinical ethics consultation. This perspective provides an appreciation of ethical tensions that will exist beyond the consult question into the moral space of patient care. These tensions exist even when an ethically preferable plan of action is identified. Ethically appropriate courses of action can still lead to moral dilemmas for others. The nurse ethicist provides a lens well suited to identify and respond to these dilemmas. The nurse-patient relationship is the ethical foundation of nursing practice and this relational ontology is well suited to addressing ethical dilemmas that exist prior to and beyond the initial consult question. This paper will describe one nurse ethicist's phronetic and pragmatic approach to a clinical ethics consult elucidated through feminist ethics and systems thinking. This paper will describe the theoretical basis for this method, present a case, and describe how this consultation approach provides a rich analysis based around relationships and responsibilities that also highlights the important ethical tensions within the social structure that exists around the patient and continue after the consult question is answered.

Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease.

BACKGROUND: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach. METHODS: Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end-induction were stratified according to the post-induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post-induction "bridge" therapy before ASCT (cohort 2), and 3) post-induction therapy without ASCT (cohort 3). χ2 tests were used to compare patient characteristics. Three-year event-free survival (EFS) and overall survival (OS) were estimated by the Kaplan-Meier method and survival curves were compared by log-rank test. RESULTS: The study cohort consisted of 201 patients: cohort 1 (n = 123), cohort 2 (n = 51), and cohort 3 (n = 27). Although the end-induction response was better for cohort 1 than cohorts 2 and 3, the outcomes for cohorts 1 and 2 were not significantly different (P = .77 for EFS and P = .85 for OS). Inferior outcomes were observed for cohort 3 (P < .001 for EFS and P = .06 for OS). Among patients with end-induction stable metastatic disease, 3-year EFS was significantly improved for cohort 2 versus cohort 1 (P = .04). Cohort 3 patients with a complete response at metastatic sites after post-induction therapy had significantly better 3-year EFS than those with residual metastatic disease (P = .01). CONCLUSIONS: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.

Accrual Trends for Children's Oncology Group Clinical Trials: A Single Center Experience.

Children's Oncology Group (COG) has been highly successful in improving childhood cancer survival through well-designed multi-institutional clinical trials. However, our center has recognized a decline in the number of enrollments on COG therapeutic clinical trials over recent years. Our single center, retrospective analysis evaluated in detail the patient enrollment rates, annual number of available clinical trials and reason for nonenrollment over the last decade. We found a 61% decrease in enrollment for phase II to III trials of newly diagnosed patients at our center (2011-2018) along a 29% decrease in the number of open COG studies annually. The primary reason for nonenrollment was unavailability of a suitable trial (76%). We also recognized a decrease in number of adolescent and young adult enrollment particularly in the last 8 years (2010-2018); however, the enrollment rate for adolescent and young adults was not substantially different than enrollment of children. The reasons for reduced enrollments are most likely multifactorial and complex. It is imperative that we continue to develop novel clinical studies using a portfolio of federal, investigator-initiated, and industry trials for pediatric oncology patients to continue to advance outcomes, study survivorship, and improve quality of life for these patients.

Nurses as Disciplinary Agents of the State: Ethical Practice and Mandatory Reporting in the United States.

This article reviews legislative initiatives that mandate nurses to report patients, families, and clinicians to law enforcement. Most recently, these laws target transgender and gender diverse (TGD) youth and people seeking abortion. In this article, we examine the ethics of such laws through professional ethical codes. Furthermore, through a biopolitical lens, we critically analyze examples of nurses' participation in complying with laws that harm patients. Finally, we discuss the damage these laws have on the nursing profession and assert the necessity of a resituating of professional ethics that considers the complexity of nursing care amidst increasingly blatant state-sanctioned violence.

Antiracism: An Ethical Imperative.

Pediatric ethicists hold a privileged position of influence within health care institutions. Such a position confers a corresponding responsibility to address barriers to the health and flourishing of all children. A major barrier to children's health is racism. Pediatric ethicists can, and should, leverage their position to address racism both in institutional policy and the provision of pediatric care. Health care's historical and continued contributions to fostering and sustaining racist values and systems mean that those within all medical fields- regardless of race, ethnicity, gender, age, or profession-should consider ways they can work to offset and ultimately dismantle those values and systems. Institutional policy is a critical mechanism propagating racism in hospitals and an area where ethicists have a unique perspective to bring antiracism into ethical analysis. Many institutional and organizational policies have unintended consequences, negatively impacting children and families who have been historically marginalized and oppressed. In this paper, we report and discuss existing policies, along with how they are implemented (procedures) and how they are conducted (practices), identified through a workshop during a pediatric subgroup meeting at an annual bioethics conference. We highlight the need to focus on these structural factors and reference scholarship that can be used to correct institutional policies that uphold white supremacy. We conclude with actionable, concrete recommendations for change.

Parental request for non-resuscitation in fetal myelomeningocele repair: an analysis of the novel ethical tensions in fetal intervention.

As the field of fetal intervention grows, novel ethical tensions will arise. We present a case of Fetal myelomeningocele repair involving a 25-week fetus where parents requested that if emergent delivery was necessary during the open uterine procedure, that the medical team did not perform resuscitation. This question brings forward an important discussion around the complicated space of maternal autonomy, child rights, and clinician obligations that exists in fetal intervention. In some regions, a mother in this situation may choose to terminate the pregnancy. Parents could also choose not to do the surgery. Parents in some regions could opt for no resuscitation of a child born at 25-weeks' gestation. We offer an analysis of these relevant considerations, the different tensions, and the conflicting duties between the mother, fetus, and medical team. This analysis will provide ethical and clinical guidance for future questions that may arise in this burgeoning field.

Active or passive guidance? Decision-making in fetal health consultation.

Prenatal consults are full of uncertainty. But, what are physicians contributing to this, and what is parents understanding of the intricacies of the complex decisions we present to them? Might the way we actively or passively guide parents affect how they make decisions in the complex world of fetal health consultations? For instance, how does "recommending" versus "not recommending" impact how parents view their choices? Reviewing the literature, there is a paucity of data on this topic. There are studies detailing experience but not of how guidance affects decision-making. We review some of this literature and discuss concepts relevant to this observation. We hypothesize that passive or active guidance by fetal health consultation members influences the moral deliberation and ethical decision-making of parents in different ways and propose a possible research idea.

Should Tactile Defensiveness Exclude a Life-Sustaining Intervention in an Adolescent With Autism?

This Ethics Rounds considers the benefits and burdens of a potentially temporary tracheostomy in an adolescent with autism and severe tactile defensiveness.

SARS-CoV-2 Monoclonal Antibodies in Children: Ethical Considerations.

The use of monoclonal antibodies in children with certain conditions and at high risk for severe COVID-19 has been approved by the US Food and Drug Administration under the Emergency Use Authorization mechanism of the Federal Food, Drug, and Cosmetic Act. No data on the tolerability or efficacy of these therapies in persons <18 years of age are available; there is risk. Whether they will work is unknown, but they could. A disproportionate number of these children who meet the criteria for treatment with mAbs are from communities of black, Native American, and other race. How should health systems, hospitals, and clinicians balance the tensions between being seen as experimenting with an untested drug as opposed to withholding a potentially life-saving treatment? This article identifies, analyzes, and makes recommendations on the methods by which health systems, hospitals, and individual clinicians can ethically balance these tensions.

Exploration and Ethical Analysis of Open-label Pediatric Vaccine Trials in a Pandemic.

Young children will ultimately need to be vaccinated to stop the spread of coronavirus disease 2019 (COVID-19). Initial studies of vaccine were performed in adults. Randomized controlled trials are the gold standard. In the COVID-19 pandemic, many questions need to be answered about the ethics and feasibility of these trials. Given the harms of the COVID-19 pandemic and the now-known efficacy of the vaccines in adults and teens, the question of whether clinical equipoise exists for a placebo-controlled trial of vaccines in younger children remains. Parents may be reluctant to enroll children in these trials because they want their child to receive the vaccine or because they are worried about vaccines or clinical trials in general. One option for gathering data on tolerability and efficacy in children would be to use a nonrandomized trial to enroll parents willing to vaccinate their children and those who are hesitant. We discuss the advantages and disadvantages of such an open-label trial that could provide guidance for future pandemics. (Clin Ther.

Pandemic-Related Shifts in New Patients Admitted to Children's Hospitals.

OBJECTIVES: During the coronavirus disease 2019 pandemic, professional organizations recommended preferential transfer of pediatric patients from general hospitals to children's hospitals. Patients previously receiving all care at other facilities would be new to children's hospitals. As a proxy for care consolidation, we sought to describe changes in new patient encounters at children's hospitals and test associations between local severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidences and new patient encounters. METHODS: This retrospective cohort study included patients aged 6 months to 18 years admitted to children's hospitals from March 15, 2019, to June 30, 2019 (control) and 2020 (pandemic period). Primary outcome was odds ratio of being a new versus established patient by study period. Generalized linear models estimated odds of being a new patient with adjustment for diagnosis. Analyses were also stratified by local SARS-CoV-2 transmission. RESULTS: There were 205 283 encounters (45.3% new patients). New patients were more common in the pandemic period than in the control (46.4 vs 44.7%, OR 1.07, 95% confidence interval [CI]: 1.05 to 1.09). After adjusting for diagnosis, pandemic new patients were no more common than control new patients (adjusted odds ratio 1.00, 95% CI: 0.98 to 1.02). Compared with hospitals experiencing low local SARS-CoV-2 transmission, admission encounters at both medium and high transmission hospitals were more likely to be new (adjusted odds ratio 1.08, 95% CI: 1.03 to 1.14 and 1.09, 95% CI: 1.03 to 1.15, respectively). CONCLUSIONS: During the early coronavirus disease 2019 pandemic, proportional increases in new patients to children's hospitals appeared to be due to changes in diagnoses but were also associated with local SARS-CoV-2 transmission. Pediatric care consolidation may have occurred; how this may have impacted outcomes for hospitalized children is unclear.

On "Not Recommending" ECMO.

The neonatologist was describing the dire situation, the complexity of the fetus's anomalies, and the options-comfort care, some resuscitation-and finished by saying, "We would not recommend ECMO …" "We would not recommend" is a curious phrase. There is something ambiguous, very nebulous about it, something passive, noncommittal, maybe even deflective. As a bioethics researcher, I wondered how this phrase is interpreted, how it influences parents' moral deliberation over their options.

Our Next Pandemic Ethics Challenge? Allocating "Normal" Health Care Services.

The pandemic creates unprecedented challenges to society and to health care systems around the world. Like all crises, these provide a unique opportunity to rethink the fundamental limiting assumptions and institutional inertia of our established systems. These inertial assumptions have obscured deeply rooted problems in health care and deflected attempts to address them. As hospitals begin to welcome all patients back, they should resist the temptation to go back to business as usual. Instead, they should retain the more deliberative, explicit, and transparent ways of thinking that have informed the development of crisis standards of care. The key lesson to be learned from those exercises in rational deliberation is that justice must be the ethical foundation of all standards of care. Justice demands that hospitals take a safety-net approach to providing services that prioritizes the most vulnerable segments of society, continue to expand telemedicine in ways that improve access without exacerbating disparities, invest in community-based care, and fully staff hospitals and clinics on nights and weekends.

Electronic DNA Analysis of CSF Cell-free Tumor DNA to Quantify Multi-gene Molecular Response in Pediatric High-grade Glioma.

PURPOSE: Pediatric high-grade glioma (pHGG) diagnosis portends poor prognosis and therapeutic monitoring remains difficult. Tumors release cell-free tumor DNA (cf-tDNA) into cerebrospinal fluid (CSF), allowing for potential detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of cf-tDNA with a handheld platform (Oxford Nanopore MinION) could quantify patient-specific CSF cf-tDNA variant allele fraction (VAF) with improved speed and limit of detection compared with established methods. EXPERIMENTAL DESIGN: We performed ultra-short fragment (100-200 bp) PCR amplification of cf-tDNA for clinically actionable alterations in CSF and tumor samples from patients with pHGG (n = 12) alongside nontumor CSF (n = 6). PCR products underwent rapid amplicon-based sequencing by Oxford Nanopore Technology (Nanopore) with quantification of VAF. Additional comparison to next-generation sequencing (NGS) and droplet digital PCR (ddPCR) was performed. RESULTS: Nanopore demonstrated 85% sensitivity and 100% specificity in CSF samples (n = 127 replicates) with 0.1 femtomole DNA limit of detection and 12-hour results, all of which compared favorably with NGS. Multiplexed analysis provided concurrent analysis of H3.3A (H3F3A) and H3C2 (HIST1H3B) mutations in a nonbiopsied patient and results were confirmed by ddPCR. Serial CSF cf-tDNA sequencing by Nanopore demonstrated correlation of radiological response on a clinical trial, with one patient showing dramatic multi-gene molecular response that predicted long-term clinical response. CONCLUSIONS: Nanopore sequencing of ultra-short pHGG CSF cf-tDNA fragments is feasible, efficient, and sensitive with low-input samples thus overcoming many of the barriers restricting wider use of CSF cf-tDNA diagnosis and monitoring in this patient population.

Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma.

Pediatric and adult high-grade gliomas (HGGs) frequently harbor PDGFRA alterations. We hypothesized that cotreatment with everolimus may improve the efficacy of dasatinib in PDGFRα-driven glioma through combinatorial synergism and increased tumor accumulation of dasatinib. We performed dose-response, synergism, P-glycoprotein inhibition, and pharmacokinetic studies in in vitro and in vivo human and mouse models of HGG. Six patients with recurrent PDGFRα-driven glioma were treated with dasatinib and everolimus. We found that dasatinib effectively inhibited the proliferation of mouse and human primary HGG cells with a variety of PDGFRA alterations. Dasatinib exhibited synergy with everolimus in the treatment of HGG cells at low nanomolar concentrations of both agents, with a reduction in mTOR signaling that persisted after dasatinib treatment alone. Prolonged exposure to everolimus significantly improved the CNS retention of dasatinib and extended the survival of PPK tumor-bearing mice (mutant TP53, mutant PDGFRA, H3K27M). Six pediatric patients with glioma tolerated this combination without significant adverse events, and 4 patients with recurrent disease (n = 4) had a median overall survival of 8.5 months. Our results show that the efficacy of dasatinib treatment of PDGFRα-driven HGG was enhanced with everolimus and suggest a promising route for improving targeted therapy for this patient population.