Interactions With Police in the Emergency Care of Children: Ethical and Legal Considerations.

OBJECTIVES: Emergency medicine providers may interface with law enforcement personnel (LEP) on behalf of their pediatric patients for a variety of reasons, from reporting child abuse to caring for children who are in police custody. Given the unique nature of caring for minors who may not have legal or medical autonomy, interactions with LEP can raise ethical concerns for emergency providers, specifically with regard to legal representation, developmental immaturity, and the civil rights of children and their parents/guardians. METHODS: We review 4 patient scenarios, based on real cases experienced by the authors, to demonstrate the legal and ethical issues that may arise when LEP are involved in the emergency care of a child. These scenarios discuss parental/guardian visitation for children in police custody in the emergency department (ED), the practice of making arrests on hospital grounds, and police interviews of children in the ED. RESULTS: Using the ethical principles of autonomy, beneficence, and justice, we offer recommendations for emergency providers on how to advocate for their pediatric patients in LEP custody within the constraints and protections of the law. We also suggest best practices for hospital systems to develop policies surrounding LEP activity in the ED. CONCLUSIONS: These nuanced situations require careful advocacy for the child and a collaborative approach between medical providers and LEP to balance the child's well-being with public safety. We offer recommendations here, and we maintain that clear, widely adopted best practices for the care of minors in LEP custody are long overdue.

Aortic recoarctation and pseudoaneurysm five decades after repair.

BACKGROUND: Coarctation of the aorta is a congenital cardiac defect characterized by a narrowing of the proximal thoracic aorta. Despite excellent long-term results, surgical repair is rarely complicated by recoarctation. METHODS/RESULTS: We describe a case with the longest time to reintervention to date, featuring surgical repair of delayed aortic recoarctation and pseudoaneurysm 53 years after the initial operation. DISCUSSION: This case emphasizes the need for lifelong surveillance in this patient population and exemplifies a multidisciplinary approach in evaluating treatment options of complex aortic pathology, including open and endovascular considerations.

A Case of Toxic Breast-feeding?

Opiates are frequently prescribed postpartum for pain relief after cesarean delivery, episiotomies, and headaches. It is estimated that greater than 30% of breast-feeding mothers in the United States are prescribed opiates for pain relief associated with childbirth. Many opiates are readily transferred to human milk, although life-threatening events are rare. We report a 6-day-old breast-feeding infant whose mother was taking hydromorphone for pain relief from a cesarean delivery and whose clinical course was suggestive of opiate toxicity. This case emphasizes the importance of thorough medication history taking in postpartum breast-feeding mothers whose infants may present with symptoms of opiate toxicity. Semisynthetic opiates are frequently not detected on emergency department urine toxicology screens. The pertinent literature is reviewed.

A Highly Active Isoform of Lentivirus Restriction Factor SAMHD1 in Mouse.

The triphosphohydrolase SAMHD1 (sterile α motif and histidine-aspartate domain-containing protein 1) restricts HIV-1 replication in nondividing myeloid cells by depleting the dNTP pool, preventing reverse transcription. SAMHD1 is also reported to have ribonuclease activity that degrades the virus genomic RNA. Human SAMHD1 is regulated by phosphorylation of its carboxyl terminus at Thr-592, which abrogates its antiviral function yet has only a small effect on its phosphohydrolase activity. In the mouse, SAMHD1 is expressed as two isoforms (ISF1 and ISF2) that differ at the carboxyl terminus due to alternative splicing of the last coding exon. In this study we characterized the biochemical and antiviral properties of the two mouse isoforms of SAMHD1. Both are antiviral in nondividing cells. Mass spectrometry analysis showed that SAMHD1 is phosphorylated at several amino acid residues, one of which (Thr-634) is homologous to Thr-592. Phosphomimetic mutation at Thr-634 of ISF1 ablates its antiviral activity yet has little effect on phosphohydrolase activity in vitro dGTP caused ISF1 to tetramerize, activating its catalytic activity. In contrast, ISF2, which lacks the phosphorylation site, was significantly more active, tetramerized, and was active without added dGTP. Neither isoform nor human SAMHD1 had detectable RNase activity in vitro or affected HIV-1 genomic RNA stability in newly infected cells. These data support a model in which SAMHD1 catalytic activity is regulated through tetramer stabilization by the carboxyl-terminal tail, phosphorylation destabilizing the complexes and inactivating the enzyme. ISF2 may serve to reduce the dNTP pool to very low levels as a means of restricting virus replication.

Degradation of SAMHD1 by Vpx Is Independent of Uncoating.

UNLABELLED: Sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid and resting T cells. Lentiviruses such as HIV-2 and some simian immunodeficiency viruses (SIVs) counteract the restriction by encoding Vpx or Vpr, accessory proteins that are packaged in virions and which, upon entry of the virus into the cytoplasm, induce the proteasomal degradation of SAMHD1. As a tool to study these mechanisms, we generated HeLa cell lines that express a fusion protein termed NLS.GFP.SAM595 in which the Vpx binding domain of SAMHD1 is fused to the carboxy terminus of green fluorescent protein (GFP) and a nuclear localization signal is fused to the amino terminus of GFP. Upon incubation of Vpx-containing virions with the cells, the NLS.GFP.SAM595 fusion protein was degraded over several hours and the levels remained low over 5 days as the result of continued targeting of the CRL4 E3 ubiquitin ligase. Degradation of the fusion protein required that it contain a nuclear localization sequence. Fusion to the cytoplasmic protein muNS rendered the protein resistant to Vpx-mediated degradation, confirming that SAMHD1 is targeted in the nucleus. Virions treated with protease inhibitors failed to release Vpx, indicating that Gag processing was required for Vpx release from the virion. Mutations in the capsid protein that altered the kinetics of virus uncoating and the Gag binding drug PF74 had no effect on the Vpx-mediated degradation. These results suggest that Vpx is released from virions without a need for uncoating of the capsid, allowing Vpx to transit to the nucleus rapidly upon entry into the cytoplasm. IMPORTANCE: SAMHD1 restricts lentiviral replication in myeloid cells and resting T cells. Its importance is highlighted by the fact that viruses such as HIV-2 encode an accessory protein that is packaged in the virion and is dedicated to inducing SAMHD1 degradation. Vpx needs to act rapidly upon infection to allow reverse transcription to proceed. The limited number of Vpx molecules in a virion also needs to clear the cell of SAMHD1 over a prolonged period of time. Using an engineered HeLa cell line that expresses a green fluorescent protein (GFP)-SAMHD1 fusion protein, we showed that the Vpx-dependent degradation occurs without a need for viral capsid uncoating. In addition, the fusion protein was degraded only when it was localized to the nucleus, confirming that SAMHD1 is targeted in the nucleus and thus explaining why Vpx also localizes to the nucleus.

SAMHD1 has differential impact on the efficacies of HIV nucleoside reverse transcriptase inhibitors.

Sterile alpha motif- and histidine/aspartic acid domain-containing protein 1 (SAMHD1) limits HIV-1 replication by hydrolyzing deoxynucleoside triphosphates (dNTPs) necessary for reverse transcription. Nucleoside reverse transcriptase inhibitors (NRTIs) are components of anti-HIV therapies. We report here that SAMHD1 cleaves NRTI triphosphates (TPs) at significantly lower rates than dNTPs and that SAMHD1 depletion from monocytic cells affects the susceptibility of HIV-1 infections to NRTIs in complex ways that depend not only on the relative changes in dNTP and NRTI-TP concentrations but also on the NRTI activation pathways.

Inhibition of CUL4A Neddylation causes a reversible block to SAMHD1-mediated restriction of HIV-1.

The deoxynucleoside triphosphohydrolase SAMHD1 restricts retroviral replication in myeloid cells. Human immunodeficiency virus type 2 (HIV-2) and a simian immunodeficiency virus from rhesus macaques (SIVmac) encode Vpx, a virion-packaged accessory protein that counteracts SAMHD1 by inducing its degradation. SAMHD1 is thought to work by depleting the pool of intracellular deoxynucleoside triphosphates but has also been reported to have exonuclease activity that could allow it to degrade the viral genomic RNA or viral reverse-transcribed DNA. To induce the degradation of SAMHD1, Vpx co-opts the cullin4a-based E3 ubiquitin ligase, CRL4. E3 ubiquitin ligases are regulated by the covalent attachment of the ubiquitin-like protein Nedd8 to the cullin subunit. Neddylation can be prevented by MLN4924, a drug that inhibits the nedd8-activating enzyme. We report that MLN4924 inhibits the neddylation of CRL4, blocking Vpx-induced degradation of SAMHD1 and maintaining the restriction. Removal of the drug several hours postinfection released the block. Similarly, Vpx-containing virus-like particles and deoxynucleosides added to the cells more than 24 h postinfection released the SAMHD1-mediated block. Taken together, these findings support deoxynucleoside triphosphate pool depletion as the primary mechanism of SAMHD1 restriction and argue against a nucleolytic mechanism, which would not be reversible.

The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus.

Sterile alpha motif domain- and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase that restricts the replication of lentiviruses in myeloid cells by hydrolyzing the cellular deoxynucleotide triphosphates to a level below that which is required for reverse transcription. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) encode the accessory protein viral protein X (Vpx) that counteracts SAMHD1. Vpx recruits SAMHD1 to a cullin4A-RING E3 ubiquitin ligase (CRL4), which targets the enzyme for proteasomal degradation. Vpx and SAMHD1 both localize to the nucleus of the cell. We identified the nuclear localization sequence (NLS) of SAMHD1 as a conserved KRPR sequence at amino acid residues 11 to 14. SAMHD1 lacking a functional NLS localized to the cytoplasm but retained its triphosphohydrolase and antiviral activities. However, cytoplasmic SAMHD1 was resistant to Vpx-induced degradation, and its antiviral activity was not counteracted by Vpx. Cytoplasmic SAMHD1 interacted with Vpx and retained it in the cytoplasm. The inhibition of nuclear export with leptomycin B did not impair the ability of Vpx to degrade SAMHD1. These findings suggest that SAMHD1 is targeted by Vpx for ubiquitination and degradation in the nucleus.

Pediatric procedural sedation in African clinical settings: A mixed methods study of African providers' sedation practices.

Background: Little is known about the practice of pediatric procedural sedation in Africa, despite being incredibly useful to the emergency care of children. This study describes the clinical experiences of African medical providers who use pediatric procedural sedation, including clinical indications, medications, adverse events, training, clinical guideline use, and comfort level. The goals of this study are to describe pediatric sedation practices in resource-limited settings in Africa and identify potential barriers to the provision of safe pediatric sedation. Methods: This mixed methods study describes the pediatric procedural sedation practices of African providers using semi-structured interviews. Purposive sampling was used to identify key informants working in African resource-limited settings across a broad geographic, economic, and professional range. Quantitative data about provider background and sedation practices were collected concurrently with qualitative data about perceived barriers to pediatric procedural sedation and suggestions to improve the practice of pediatric sedation in their settings. All interviews were transcribed, coded, and analyzed for major themes. Results: Thirty-eight key informants participated, representing 19 countries and the specialties of Anesthesia, Surgery, Pediatrics, Critical Care, Emergency Medicine, and General Practice. The most common indication for pediatric sedation was imaging (42%), the most common medication used was ketamine (92%), and hypoxia was the most common adverse event (61%). Despite 92% of key informants stating that pediatric procedural sedation was critical to their practice, only half reported feeling adequately trained. The three major qualitative themes regarding barriers to safe pediatric sedation in their settings were: lack of resources, lack of education, and lack of standardization across sites and providers. Conclusions: The results of this study suggest that training specialized pediatric sedation teams, creating portable "pediatric sedation kits," and producing locally relevant pediatric sedation guidelines may help reduce current barriers to the provision of safe pediatric sedation in resource-limited African settings.

More Than Just a Passport: Resources and Implementation Strategies to Optimize Preparation for Global Health Work.

During the past decade, many resources have been developed to support trainees and clinicians seeking to prepare for global health work. For time-constrained health care providers, figuring out how to prepare can be overwhelming. Given the wide variation in types of travelers and work plans, there is not a "one size fits all" preparation resource. This article offers a summary of preparation topics that all travelers should consider; compiles curated, high-yield resources designed to prepare health care providers for global health experiences; and provides implementation strategies to best meet the unique needs of each traveler, taking into consideration factors such as provider expertise (trainee vs practicing clinician), solo versus group travel, and time available before departure. These curated resources include a variety of training modalities (self-directed, group-based, train-the-trainer, and in-person courses), all summarized here to empower health care providers to create individualized, comprehensive preparation plans before engaging globally. [Pediatr Ann. 2023;52(9):e330-e334.].

Valve-sparing root replacement after the Ross procedure.

OBJECTIVES: The Ross procedure is a preferred treatment for infants and children with aortic valve disease. Progressive neoaortic root dilation and neoaortic insufficiency can occur after the Ross procedure, and because of the young age of these patients, valve-sparing aortic root replacement procedures have advantages compared with the Bentall procedure. The aim of this study is to describe our experience with different techniques of aortic valve-sparing root replacement in this unique cohort of patients. METHODS: Patients undergoing valve-sparing aortic root replacement with a history of the Ross procedure between January 2001 and March 2021 were identified. A retrospective chart review was performed, and clinical characteristics of these patients were analyzed. The results of different types of valve-sparing aortic root replacement were also compared. RESULTS: Forty-two patients who had previously undergone a Ross procedure in childhood presented for reintervention for neoaortic root or valve pathology. Seventeen of these patients were considered for valve-sparing aortic root replacement but underwent bioprosthetic or mechanical valve replacement, and 25 patients underwent successful valve-sparing aortic root replacement. Patients who underwent valve-sparing aortic root replacement received a traditional aortic root remodeling procedure with or without suture annuloplasty (Yacoub technique, group 1, n = 7), an aortic root reimplantation procedure (David technique, group 2, n = 11), or a modified root remodeling procedure that also used a geometric annuloplasty ring (group 3, n = 7). Patient demographics and comorbidities were similar between groups. Mean follow-up for these 3 cohorts was 14 years, 4 years, and 1 year, respectively. Overall survival was good, with 1 early death due to hemorrhage in group 2 and 1 death due to malignancy in group 1. Eight patients (7 in group 1; 1 in group 2) required subsequent aortic valve replacements due to neoaortic insufficiency, whereas none in group 3 have required any reintervention. Overall, patients requiring valve replacement after valve-sparing aortic root replacement had lower grades of preoperative neoaortic insufficiency and higher grades of postoperative neoaortic insufficiency. Greater than mild postoperative neoaortic insufficiency was associated with the need for subsequent neoaortic valve replacement. CONCLUSIONS: Valve-sparing aortic root replacement is safe in patients with a prior Ross procedure. Reimplantation offers superior durability compared with the traditional remodeling procedure. Greater than mild neoaortic insufficiency on postoperative echocardiogram should prompt additional attempts at valve repair. A modified remodeling procedure with geometric ring annuloplasty that is personalized to the patient's individual anatomy is safe with good short-term results, but longer follow-up is needed.

Surgical outcomes of patients at prohibitive risk who are reconsidered for surgery.

Objectives: Transcatheter treatment of advanced mitral and tricuspid valve disease is largely limited to patients at prohibitive surgical risk, although many are not candidates for transcatheter treatment. Here, we describe surgical outcomes of patients at prohibitive risk who were ineligible for transcatheter therapies to guide surgeons in management of this unique population. Methods: Patients at prohibitive risk, defined per surgeon or cardiologist discretion, who were initially referred for a transcatheter mitral or tricuspid intervention in a multidisciplinary atrioventricular valve clinic, were identified from 2019 to 2022. Preoperative risk, operative outcomes, and long-term mortality were evaluated. Results: A total of 337 patients at prohibitive risk were referred for evaluation in a multidisciplinary atrioventricular valve clinic. Of those, 161 underwent transcatheter therapy, 130 patients underwent continued medical management, and 45 were reevaluated and had high-risk surgery. Among surgical patients, 51% were women with a median age of 76 years (quartile 1-quartile 3, 65-81 years). Most patients presented in heart failure (83%; n = 37 out of 45), and 73% were in New York Heart Association functional class III or IV. Most patients (94%; n = 43) had a mitral valve intervention, of whom 56% (24 out of 43) had a mitral valve replacement. The 30-day mortality rate was 4% (2 out of 45) and major morbidity occurred in 33% (15 out of 45). By Kaplan-Meier analysis, 1-year survival was 86% ± 9%. Conclusions: Select patients at prohibitive risk who were ineligible for transcatheter mitral or tricuspid valve intervention underwent surgery with overall low operative mortality and excellent 1-year survival. Patients a prohibitive risk whose anatomy is not amenable to transcatheter devices should be reconsidered for surgery.

Nontechnical Skills for Intraoperative Team Members.

Nontechnical skills, defined as the set of cognitive and social skills used by individuals and teams to reduce error and improve performance in complex systems, have become increasingly recognized as a key contributor to patient safety. Efforts to characterize, quantify, and teach nontechnical skills in the context of perioperative care continue to evolve. This review article summarizes the essential behaviors for safety, described in taxonomies for nontechnical skills assessments developed for intraoperative clinical team members (eg, surgeons, anesthesiologists, scrub practitioners, perfusionists). Furthermore, the authors describe emerging methods to advance understanding of the impact of nontechnical skills on perioperative outcomes.

Paediatric trauma education in low- and middle-income countries: A systematic literature review.

Background: Trauma-specific training improves clinician comfort and reduces patient morbidity and mortality; however, curricular content, especially with regard to paediatric trauma, varies greatly by region and income status. We sought to understand how much paediatric education is included in trauma curricula taught in low- and middle-income countries (LMICs). Methods: We conducted a systematic literature review in October 2020 and in July 2022 based on PRISMA guidelines, utilizing seven databases: MEDLINE, Scopus, Web of Science, CINAHL, Cochrane Reviews, Cochrane Trials, and Global Index Medicus. Reports were limited to those from World Bank-designated LMICs. Key information reviewed included use of a trauma curriculum, patient-related outcomes, and provider/participant outcomes. Results: The search yielded 2008 reports, with 987 included for initial screening. Thirty-nine of these were selected for review based on inclusion criteria. Sixteen unique trauma curricula used in LMICs were identified, with only two being specific to paediatric trauma. Seven of the adult-focused trauma programmes included sections on paediatric trauma. Curricular content varied significantly in educational topics and skills assessed. Among the 39 included curricula, 33 were evaluated based on provider-based outcomes and six on patient-based outcomes. All provider-based outcome reports showed increased knowledge acquisition and comfort. Four of the five patient-based outcome reports showed reduction in trauma-related morbidity and mortality. Conclusion: Trauma curricula in LMICs positively impact provider knowledge and may decrease trauma-related morbidity and mortality; however, there is significant variability in existing trauma curricula regarding to paediatric-specific content. Trauma education in LMICs should expand paediatric-specific education, as this population appears to be underserved by most existing curricula.

Five days of fever and myocardial inflammation.

Multisystem inflammatory syndrome in children is an emerging pediatric illness associated with severe acute respiratory syndrome coronavirus 2 infection. The syndrome is rare, and evidence-based guidelines are lacking. This report reviews a patient who presented for medical care multiple times early in the course of his illness, thus offering near-daily documentation of symptoms and laboratory abnormalities. The patient did not have thrombocytopenia, anemia, or myocardial inflammation until the fifth day of fever. These laboratory abnormalities coincided with the onset of rash, conjunctival injection, vomiting, and diarrhea: clinical signs that could serve as indicators for when to obtain blood tests. The timing of this patient's onset of multisystem involvement suggests that testing for multisystem inflammatory syndrome in children after only 24 h of fever, as the Centers for Disease Control and Prevention recommends, may yield false-negative results. Testing for multisystem inflammatory syndrome in children after 4 days of fever may be more reliable.

The effects of mobile health on emergency care in low- and middle-income countries: A systematic review and narrative synthesis.

BACKGROUND: In resource-constrained settings, mobile health (mHealth) has varied applications. While there is strong evidence for its use in chronic disease management, the applications of mHealth for management of acute illness in low- and middle-income countries (LMICs) are not as well described. This review systematically explores current available evidence on the effectiveness of mHealth interventions at improving health outcomes in emergency care settings in LMICs. METHODS: A systematic search of the literature was performed in accordance with PRISMA guidelines, utilizing seven electronic databases and manual searches to identify peer-reviewed literature containing each of three search elements: mHealth, emergency care (EC), and LMICs. Articles quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. RESULTS: After removing duplicates, 6498 studies met initial search criteria; 108 were eligible for full text review and 46 met criteria for inclusion. Thirty-six pertained to routine emergency care, and 10 involved complex humanitarian emergencies. Based on the GRADE criteria, 15 studies were rated as "Very Low" quality, 24 as "Low" quality, 6 as "Moderate" quality, and 1 as "High" quality. Eight studied data collection, 9 studied decision support, 15 studied direct patient care, and 14 studied health training. All 46 studies reported positive impacts of mHealth on EC in LMICs. CONCLUSIONS: Mobile health interventions can be effective in improving provider-focused and patient-centered outcomes in both routine and complex EC settings. Future investigations focusing on patient-centered outcomes are needed to further validate these findings.