Antibiotic Indications and Appropriateness in the Pediatric Intensive Care Unit: A 10-Center Point Prevalence Study.

BACKGROUND: Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking. METHODS: We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric. RESULTS: Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), nonoperative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community-acquired pneumonia (CAP; 118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range, 19%-43%). CONCLUSIONS: Most PICU patients receive antibiotics. Based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed.

An ethical analysis of obesity as a contraindication to pediatric liver transplant candidacy.

Childhood obesity is becoming more prevalent in the United States (US) and worldwide, including among children in need of a liver transplant. Unlike with heart and kidney failure, end-stage liver disease (ESLD) is unique in that no widely available medical technology can re-create the life-sustaining function of a failing liver. Therefore, delaying a life-saving liver transplant for weight loss, for example, is much harder, if not impossible for many pediatric patients, especially those with acute liver failure. For adults in the United States, guidelines consider obesity a contraindication to liver transplant. Although formal guidelines are lacking in children, many pediatric transplant centers also consider obesity a contraindication to a pediatric liver transplant. Variations in practice among pediatric institutions may result in biased and ad hoc decisions that worsen healthcare inequities. In this article, we define and report the prevalence of childhood obesity among children with ESLD, review existing guidelines for liver transplant in adults with obesity, examine pediatric liver transplant outcomes, and discuss the ethical considerations of using obesity as a contraindication to pediatric liver transplant informed by the principles of utility, justice, and respect for persons.

SARS-CoV-2 RNA positive pediatric organ donors: A case report.

BACKGROUND: Preliminary evidence suggests that non-lung organ donation from resolved, asymptomatic or mildly symptomatic SARS-CoV-2 infected adults may be safe. However, several biological aspects of SARS-CoV-2 infection differ in children and the risk for transmission and outcomes of recipients from pediatric donors with SARS-CoV-2 infection are not well described. METHODS: We report two unvaccinated asymptomatic pediatric non-lung organ deceased donors who tested positive for SARS-CoV-2 RNA by RT-PCR. Donor One unexpectedly had SARS-CoV-2 RNA detected in nasopharyngeal swab and plasma specimens at autopsy despite several negative tests (upper and lower respiratory tract) in the days prior to organ recovery. Donor Two had SARS-CoV- 2 RNA detected in multiple nasopharyngeal swabs but not lower respiratory tract specimens (endotracheal aspirate and bronchoalveolar lavage) during routine surveillance prior to organ recovery and was managed with remdesivir and monoclonal antibodies prior to organ recovery. RESULTS: Two hearts, two livers and four kidneys were successfully transplanted into seven recipients. No donor to recipient transmission of SARS-CoV-2 was observed and graft function of all organs has remained excellent for up to 7 months of followup. CONCLUSIONS: Due to the persistent gap between organ availability and the number of children waiting for transplants, deceased pediatric patients with non-disseminated SARS-CoV-2 infection, isolated to upper and/or lower respiratory tract, should be considered as potential non-lung organ donors.

An ethical analysis of obesity as a contraindication of pediatric kidney transplant candidacy.

The inclusion of body mass index (BMI) as a criterion for determining kidney transplant candidacy in children raises clinical and ethical challenges. Childhood obesity is on the rise and common among children with kidney failure. In addition, obesity is reported as an independent risk factor for the development of CKD and kidney failure. Resultantly, more children with obesity are anticipated to need kidney transplants. Most transplant centers around the world use high BMI as a relative or absolute contraindication for kidney transplant. However, use of obesity as a relative or absolute contraindication for pediatric kidney transplant is controversial. Empirical data demonstrating poorer outcomes following kidney transplant in obese pediatric patients are limited. In addition, pediatric obesity is distributed inequitably among groups. Unlike adults, most children lack independent agency to choose their food sources and exercise opportunities; they are dependent on their families for these choices. In this paper, we define childhood obesity and review (1) the association and impact of obesity on kidney disease and kidney transplant, (2) existing adult guidelines and rationale for using high BMI as a criterion for kidney transplant, (3) the prevalence of childhood obesity among children with kidney failure, and (4) the existing literature on obesity and pediatric kidney transplant outcomes. We then discuss ethical considerations related to the use of obesity as a criterion for kidney transplant.

A world away and here at home: a prioritisation framework for US international patient programmes.

Programmes serving international patients are increasingly common throughout the USA. These programmes aim to expand access to resources and clinical expertise not readily available in the requesting patients' home country. However, they exist within the US healthcare system where domestic healthcare needs are unmet for many children. Focusing our analysis on US children's hospitals that have a societal mandate to provide medical care to a defined geographic population while simultaneously offering highly specialised healthcare services for the general population, we assume that, given their mandate, priority will be given to patients within their catchment area over other patients. We argue that beyond prioritising patients within their region and addressing inequities within US healthcare, US institutions should also provide care to children from countries where access to vital medical services is unavailable or deficient. In the paper, we raise and attempt to answer the following: (1) Do paediatric healthcare institutions have a duty to care for all children in need irrespective of their place of residence, including international patients? (2) If there is such a duty, how should this general duty be balanced against the special duty to serve children within a defined geographical area to which an institution is committed, when resources are strained? (3) Finally, how are institutional obligations manifest in paradigm cases involving international patients? We start with cases, evaluating clinical and contextual features as they inform the strength of ethical claim and priority for access. We then proceed to develop a general prioritisation framework based on them.

Racism in child welfare: Ethical considerations of harm.

Racism has resulted in significant disproportionality and disparity in the US child welfare system. Being Black is not an inherent risk factor for child abuse and neglect yet Black children are almost twice as likely to be victims of substantiated abuse and neglect claims compared to other racial groups. Addressing the disproportionality within the child welfare system due to systemic racism falls squarely under the purview of bioethics. In this paper, we briefly review the impact of racism on child welfare. We then discuss some ethical considerations that mandatory healthcare reporters should think through when determining whether to report potential abuse and neglect. Specifically, we discuss the need for a broader consideration of what constitutes harm. We then present a hypothetical composite case to illuminate where and how bias can enter the process of referral to child protective services (CPS). We encourage thoughtful reporting with consideration of social and historical context and alternative explanations for worrisome findings. We recommend using evidence, avoiding assumptions by seeking clarification from families and ensuring internal consistency. When contemplating CPS referral, medical providers should feel empowered to ask questions if there is concern for potential bias. The ultimate goal is to protect children from harm. If there are clear safety concerns-they must be addressed. However, in the many cases where the safety concern is less tangible, we need to expand our considerations of the harms that can befall children, especially children of color.

An ethical analysis of obesity as a determinant of pediatric heart transplant candidacy.

BACKGROUND: Inclusion of BMI as criterion in the determination of heart transplant candidacy in children is a clinical and ethical challenge. Childhood obesity is increasing and children with heart disease are not spared. Currently, many adult heart transplant centers consider class II obesity and higher (BMI > 35 kg/m2 ) to be a relative contraindication for transplantation due to risk of poor outcome after transplant. No national guidelines exist regarding consideration of BMI in pediatric heart transplant and outcomes data are limited. This leaves decisions about transplant candidacy in obese pediatric patients to individual institutions or on a case-by-case basis, allowing for bias and inequity. METHODS: We review (a) the prevalence of childhood obesity, including among heart transplant candidates, (b) the lack of existing BMI guidelines, and (c) relevant literature on BMI and pediatric heart transplant outcomes. We discuss the ethical considerations of using obesity as a criterion using the principles of utility, justice, and respect for persons. RESULTS: Existing transplant outcomes data do not show that obese children have different or poor enough outcomes compared to non-obese children to warrant exclusion. Moreover, obesity in the United States is unequally distributed by race and socioeconomic status. Children already suffering from health disparities are therefore doubly penalized if obesity denies them access to life-saving transplant. CONCLUSION: Insufficient data exist to support using any BMI cutoff as an absolute contraindication for heart transplant in children. Attention should be paid to health equity issues when considering excluding a patient for transplant based on obesity.

Evaluation of the Therapeutic Potential of Traditionally-Used Natural Plant Extracts to Inhibit Proliferation of a HeLa Cell Cancer Line and Replication of Human Respiratory Syncytial Virus (hRSV).

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb's ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.

Resuscitate but not Intubate? Partial Codes in Pediatrics.

The use of partial code status in pediatric medicine presents clinicians with unique ethical challenges. The clinical vignette describes the presentation of a pulseless infant with a limited life expectancy. The infant's parents instruct the emergency medicine providers to resuscitate but not to intubate. In an emergency, without a clear understanding of parents' goals, complying with their request risks an ineffective resuscitation. The first commentary focuses on parental grief and how, in certain circumstances, a partial code best serves their needs. Its authors argue that providers are sometimes obligated to endure moral distress. The second commentary focuses on the healthcare team's moral distress and highlights the implications of a relational ethics framework for the case. The commentators emphasize the importance of honest communication and pain management. The final commentary explores the systems-level and how the design of hospital code status orders may contribute to requests for partial codes. They argue systems should discourage partial codes and prohibit resuscitation without intubation.

Parental Refusals of Blood Transfusions from COVID-19 Vaccinated Donors for Children Needing Cardiac Surgery.

There is a growing trend of refusal of blood transfusions from COVID-19 vaccinated donors. We highlight three cases where parents have refused blood transfusions from COVID-19 vaccinated donors on behalf of their children in the setting of congenital cardiac surgery. These families have also requested accommodations such as explicit identification of blood from COVID-19 vaccinated donors, directed donation from a COVID-19 unvaccinated family member, or use of a non-standard blood supplier. We address the ethical challenges posed by these issues. We describe the current screening and safety processes for standard blood donation and explore the importance of donor anonymity and challenges with directed donation and non-standard blood suppliers. We present an ethical framework using the Best Interest Standard, the Zone of Parental Discretion, and the Harm Principle when considering these refusals. Finally, we provide recommendations for how to approach these requests as they potentially become more commonplace in pediatrics.

Ethical Considerations in Balancing Use of Seclusion and Restraint With Risk of COVID-19 Exposure: Recommendations for Youth Inpatient Psychiatry Units.

The onset of the COVID-19 pandemic has presented unique challenges for inpatient psychiatry units (IPUs). IPUs, especially those caring for children and adolescents, rely heavily on milieu group programming to provide care and supervision for patients, and have had to adapt unit policies and procedures to maintain a therapeutic milieu while minimizing COVID-19 transmission.1 Simultaneously providing care while preventing transmission of COVID-19 within IPUs is a formidable task, and many IPUs face the additional challenge of treating youth who have been exposed to, or are actively infected with, COVID-19. In addition, given the need to prevent transmission of COVID-19, recommendations include "mandatory quarantine and isolation when patients refuse to adhere to guidelines,"2 potentially leading to the use of restraint when patients attempt to leave isolation; thus a conflict between the potential risks of enforcing infection prevention policies in order to reduce virus transmission and best practices of eliminating seclusion and restraint (S/R) creates an ethical dilemma for IPUs.

Ethical Considerations in Ever-Expanding Utilization of ECLS: A Research Agenda.

Technological advancements and rapid expansion in the clinical use of extracorporeal life support (ECLS) across all age ranges in the last decade, including during the COVID-19 pandemic, has led to important ethical considerations. As a costly and resource intensive therapy, ECLS is used emergently under high stakes circumstances where there is often prognostic uncertainty and risk for serious complications. To develop a research agenda to further characterize and address these ethical dilemmas, a working group of specialists in ECLS, critical care, cardiothoracic surgery, palliative care, and bioethics convened at a single pediatric academic institution over the course of 18 months. Using an iterative consensus process, research questions were selected based on: (1) frequency, (2) uniqueness to ECLS, (3) urgency, (4) feasibility to study, and (5) potential to improve patient care. Questions were categorized into broad domains of societal decision-making, bedside decision-making, patient and family communication, medical team dynamics, and research design and implementation. A deeper exploration of these ethical dilemmas through formalized research and deliberation may improve equitable access and quality of ECLS-related medical care.

"We Can Do Anything but We Can't Do Everything": Exploring the Perceived Impact of International Pediatric Programs on U.S. PICUs.

Purpose: Every year, an increasing number of international patients seek medical care in the United States (U.S.), yet little is known about their impact. Based on single institution experiences, we wanted to explore the perceived impact of international pediatric patients on large academic U.S. pediatric intensive care units (PICUs), as they are already taxed systems. Methods: To explore current perceptions, seven geographically diverse institutions who advertise care for international patients on their websites and have ≥24 PICU beds were identified after IRB approval was obtained. We consented and interviewed PICU division chiefs or medical directors from each institution regarding their demographics and international patients. Common themes were identified. Results: Participating institutions were diverse in geographic location, census, and resource allocation strategies. Five of the seven institutions reported the presence of a formal international patient program. Four of those five reported an increase in international patients receiving PICU care over the past 5 years. International patients sought complex surgeries, advanced cancer treatments and metabolic/genetic evaluations. We identified three primary domains that require further exploration and research: (1) cultural and language differences leading to barriers in providing optimal care to international patients (2) institutional financial considerations, and (3) perceived positive and negative impact on the care of local/domestic patient populations. Conclusions: The presence of international programs raises a number of important ethical questions, including whether clinicians have a greater duty to serve residents of the local community as opposed to international patients when resources are limited. Further exploration is warranted.