An unusual topological structure of the HIV-1 Rev response element.

Nuclear export of unspliced and singly spliced viral mRNA is a critical step in the HIV life cycle. The structural basis by which the virus selects its own mRNA among more abundant host cellular RNAs for export has been a mystery for more than 25 years. Here, we describe an unusual topological structure that the virus uses to recognize its own mRNA. The viral Rev response element (RRE) adopts an "A"-like structure in which the two legs constitute two tracks of binding sites for the viral Rev protein and position the two primary known Rev-binding sites ~55 Å apart, matching the distance between the two RNA-binding motifs in the Rev dimer. Both the legs of the "A" and the separation between them are required for optimal RRE function. This structure accounts for the specificity of Rev for the RRE and thus the specific recognition of the viral RNA.

Safety of remdesivir in the treatment of acute SARS-CoV-2 infection in pediatric patients.

BACKGROUND: Transaminase and creatinine elevations have been well described in adults treated with remdesivir for COVID-19. It is hypothesized that a similar safety profile exists in children with COVID-19 treated with remdesivir, but available data are limited, especially in children < 12 months. The primary aim of this study was to determine the prevalence and timing of elevations in transaminases and creatinine in children with COVID-19 who were treated with remdesivir. METHODS: This was a retrospective, observational cohort study including all pediatric patients admitted to a single, freestanding children's hospital who were positive for COVID-19 and received at least 1 dose of remdesivir between 1/1/2020 and 5/31/2022. Available baseline and peak transaminase and creatinine concentrations were evaluated. Multivariable logistic regression analysis was performed to identify risk factors for transaminase elevation. RESULTS: A total of 180 patients met inclusion criteria. Creatinine elevation of any grade was noted in 16% and remained elevated only in those with underlying chronic kidney disease. Transaminase elevation of any grade was noted in 58% of patients and remained elevated in only 1%. Older age and critical respiratory disease were associated with higher risk of significant transaminase elevation, whereas non-Hispanic ethnicity was strongly associated with protection against significant transaminase elevation. CONCLUSIONS: In our cohort of hospitalized children with COVID-19 who were treated with remdesivir, most patients experienced only mild transaminitis and normal creatinine concentrations. A limited number of patients experienced laboratory abnormalities which were transient, suggesting a favorable safety profile for remdesivir use in pediatrics.

Skin Testing for Penicillin Allergy: a Review of the Literature.

PURPOSE OF REVIEW: Self-reported penicillin allergies are frequently reported, though more than 95% of those are not truly allergic when challenged. These patients are more likely to receive alternative antibiotic regimens resulting in the use of broad-spectrum antibiotics that may be less effective, more toxic, and/or more expensive than preferred agents. Given the significant burden on patient outcomes and the healthcare system, the ability to reconcile an allergy and broaden future antibiotic options is essential. RECENT FINDINGS: This is a narrative review describing risk stratification for penicillin skin testing, practical advice for implementation, and future directions. A summary of studies within the last 5 years is provided. The trend over the past several years has been to offer oral drug challenges to low-risk patients and skin testing to high-risk patients with a reported penicillin allergy. This review provides support for risk stratification assessment of reported penicillin allergy to optimize antibiotic use and prevent emergence of antimicrobial resistance.

Urinary catheters: PART 2 Catheterisation in males and females.

Michelle Mitchell, Graduate Tutor for Adult Nursing, Northumbria University, michelle3.mitchell@northumbria.ac.uk and Barry Hill, Senior Lecturer in Adult Nursing, Northumbria University, describe the different catheterisation needs of men and women and the procedures to follow.

Urinary catheters PART 1.

Barry HIll, Senior Lecturer in Adult Nursing at Northumbria University ( barry.hill@northumbria.ac.uk ), and Michelle Mitchell, Graduate Tutor for Adult Nursing at Northumbria University, discuss the reasons for urinary catheterisation, the different types of catheter and the potential problems patients need to be aware of.

Ecological succession and viability of human-associated microbiota on restroom surfaces.

Human-associated bacteria dominate the built environment (BE). Following decontamination of floors, toilet seats, and soap dispensers in four public restrooms, in situ bacterial communities were characterized hourly, daily, and weekly to determine their successional ecology. The viability of cultivable bacteria, following the removal of dispersal agents (humans), was also assessed hourly. A late-successional community developed within 5 to 8 h on restroom floors and showed remarkable stability over weeks to months. Despite late-successional dominance by skin- and outdoor-associated bacteria, the most ubiquitous organisms were predominantly gut-associated taxa, which persisted following exclusion of humans. Staphylococcus represented the majority of the cultivable community, even after several hours of human exclusion. Methicillin-resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on floors but were not present in assembled Staphylococcus pan-genomes. Viral abundances, which were predominantly enterophages, human papilloma virus, and herpesviruses, were significantly correlated with bacterial abundances and showed an unexpectedly low virus-to-bacterium ratio in surface-associated samples, suggesting that bacterial hosts are mostly dormant on BE surfaces.

At a glance: urinary catheterisation in males and females.

Urinary catheterisation is a crucial procedure in healthcare, requiring a thorough understanding of the anatomical and physiological differences between males and females to ensure safe and effective care. This guide explores the anatomy of the urinary system, detailing the kidneys, ureters, bladder, and urethra, and highlights key differences in catheterisation techniques for men and women. Emphasising evidence-based practices, it discusses recent advancements, such as antimicrobial catheters, and underscores the importance of comprehensive training and competency assessments for healthcare providers. Additionally, the guide advocates for patient-centred approaches, multidisciplinary collaboration, and adherence to updated policies to reduce complications such as catheter-associated urinary tract infections (CAUTIs). By integrating these critical evaluations and best practices, health professionals can enhance patient outcomes and maintain high standards of care in urinary catheterisation.

Improving Antibiotic Use in Pediatric Preseptal Cellulitis Using a Clinical Practice Guideline.

OBJECTIVES: The purpose of this study was to evaluate the impact of a clinical practice guideline (CPG) on antibiotic use and resource utilization for pediatric preseptal cellulitis. METHODS: This retrospective quasiexperimental study included patients between the age of 2 months and 17 years admitted for preseptal cellulitis between January 2013 and December 2023. The preseptal cellulitis CPG was implemented in December 2020 using a multifaceted strategy that included buy-in from key stakeholders, education of frontline providers, the official CPG launch, and stakeholder check-ins. The primary outcome was the use of broad-spectrum antibiotics, including dual/triple therapy and methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. The secondary outcome was resource utilization including blood testing and imaging. Outcomes were compared pre- and post-CPG implementation using the Fisher exact test and logistic regressions. RESULTS: Of 236 patients meeting inclusion criteria, 175 and 61 patients composed the pre- and post-CPG cohorts, respectively. Median age (interquartile range) was 4.0 (1.8-8.3) years and 46% of the population were female. Post-CPG implementation changes in empirical antibiotic use included decreases in broad-spectrum use from 100% to 66% (P < .001), dual/triple therapy from 47% to 16% (P < .001), and MRSA active agents from 86% to 26% (P < .001). There was a decrease in complete blood count and blood culture orders from 75% to 57% (P = .014) and 32% to 18% (P = .047), respectively. CONCLUSIONS: Use of broad-spectrum antibiotics, including dual/triple therapy and MRSA active antibiotics for the treatment of pediatric preseptal cellulitis, decreased after CPG implementation.

Closer to Home: A Quality Improvement Initiative to Optimize Satellite Site Bed Capacity.

BACKGROUND: The coronavirus disease 2019 pandemic resulted in the underutilization of inpatient beds at our satellite location. A lack of clarity and standardized admission criteria for the satellite led to frequent transfers to the main campus, resulting in patients traveling larger distances to receive inpatient care. We sought to optimize inpatient resource use at the satellite campus and keep patients "closer to home" by admitting eligible patients to that inpatient unit (LA4). Our aim was to increase bed capacity use at the satellite from 45% to 70% within 10 months. Our process measure was to increase the proportion of patients needing hospitalization who presented to the satellite emergency department (ED) and were then admitted to LA4 from 76% to 85%. METHODS: A multidisciplinary team used quality improvement methods to optimize bed capacity use. Interventions included (1) the revision and dissemination of satellite admission guidelines, (2) steps to create shared understanding of appropriate satellite admissions between ED and inpatient providers, (3) directed provider feedback on preventable main campus admissions, and (4) consistent patient and family messaging about the potential for transfer. Data were collected via chart review. Annotated run charts were used to assess the impact of interventions over time. RESULTS: Average LA4 bed capacity use increased from 45% to 69%, which was sustained for 1 year. The average percentage of patients admitted from the satellite ED to LA4 increased from 76% to 84%. CONCLUSIONS: We improved bed capacity use at our satellite campus through transparent admission criteria and shared mental models of patient care needs between ED and inpatient providers.

Applying Quality Improvement Methodology to Standardize Pediatric Urinary Tract Infection Diagnosis and Management throughout a Healthcare System.

Background: Pediatric urinary tract infections (UTIs) require early diagnosis and appropriate treatment to avoid short- and long-term morbidity. Baseline data from 13,000 children across a regional health system demonstrated wide variation in UTI management, including antibiotic choice, duration, and dosing. In 2019, the local antibiotic stewardship team recommended cephalexin as the ideal first-line UTI treatment due to its effectiveness, narrow spectrum, low cost, and palatability. This project aimed to improve first-line prescription of cephalexin as an empiric antibiotic treatment for uncomplicated UTIs from 34% to 75% in children 60 days to 18 years of age presenting to any site within the healthcare system within 6 months. Methods: A multidisciplinary team of key stakeholders reviewed baseline data and developed three key drivers. These included a standardized UTI pathway, electronic health record enhancements, and provider education. Interventions were supported by a literature review and implemented via Plan-Do-Study-Act cycles with data monitored bimonthly. The primary outcome was the percentage of patients prescribed cephalexin for presumed UTI over the total number of presumed UTI diagnoses treated with empiric antibiotics throughout the healthcare system. The balancing measure included 14-day return visits for a UTI-related diagnosis across the system. Results: After the release of the updated UTI pathway, first-line cephalexin prescribing for UTI improved from 34% to 66%. There was no change in 14-day revisits for UTI. Conclusions: Standardizing the diagnosis and management of UTIs across the spectrum of coordinated care led to improved system-wide adherence to local antibiotic stewardship guidelines for empiric UTI treatment.

Facet-sparing decompression with a minimally invasive flexible microblade shaver: a prospective operative analysis.

STUDY DESIGN: This is a detailed description of a facet-sparing decompression technique and a prospective observational study of 59 subjects. OBJECTIVE: To describe a facet-sparing decompression technique, quantify operative parameters, adverse events, and anatomic changes following decompression with a flexible microblade shaving system. SUMMARY OF BACKGROUND DATA: Decompression in patients with lumbar spinal stenosis is a common surgical procedure. However, obtaining a thorough decompression while leaving enough tissue to avoid destabilization can be challenging. Decompression with a flexible, through-the-foramen system may mitigate some of these challenges. MATERIALS AND METHODS: Fifty-nine subjects diagnosed with lumbar spinal stenosis were recruited into this study. Subjects underwent decompression with a flexible, microblade decompression system at a total of 88 levels between L2 and S1. Subject demographics, details of the procedure, and operation, including adverse events were collected. Preoperative and postoperative computed tomography scans and plain radiographs were obtained from a subset of 12 subjects and quantitatively assessed for bone removal and preservation of stabilizing structures. RESULTS: Fifty-nine subjects had 88 levels treated, 51% single-level and 49% 2-level with L4-L5 being the most commonly decompressed level. Operative time, blood loss, and length of stay were similar to or less than that seen in the historical control. The system was successfully used for decompression in 95.8% of the attempted foramina. Three operative complications were reported, all dural tears (5.1%). These dural tears occurred before introduction of the flexible decompression system. Computed tomography scans from 12 subjects demonstrate access to the lateral recess and foramen with removal of <6% of the superior facet cross-sectional area. CONCLUSIONS: The flexible microblade shaving system provided thorough decompression with few intraoperative complications. Operative variables were favorable compared to the literature and radiographic decompression was achieved to a great extent while allowing for the preservation of the facet joints and midline structures.

Antibiotic treatment duration for culture-negative sepsis in the pediatric intensive care unit.

Objective: Sepsis remains a leading cause of morbidity and mortality in children. There is very limited guidance for sepsis treatment when cultures remain negative. This study sought to determine the effectiveness of short versus long course of antibiotics when treating culture-negative sepsis and assess for subsequent multidrug-resistant organism (MDRO) acquisition. Design: Retrospective cohort study. Setting: Quaternary academic children's hospital. Patients: Pediatric intensive care unit (ICU) patients with culture-negative sepsis receiving a minimum of 72 hours of antibiotics. Methods: Patients found to have culture-negative sepsis from January 2017 to May 2020 were divided into two groups: short and long course of antibiotics. Various demographic and laboratory results were collected for each subject as available. Primary outcomes included mortality and lengths of stay. The secondary outcome was subsequent acquisition of a new MDRO. Results: Eighty-six patients were treated for culture-negative sepsis with 43 patients in both the short- (< or = 7 days) and long-course (>7 days) treatment cohorts. Patients who received a short course of antibiotics had a lower overall mortality than those who received a long course (9.3% vs 25.6% p = 0.047), but there was no difference in 30-day mortality (p > 0.99). Patients in the short-course group had a shorter hospital length of stay (22 vs 30 days p = 0.018). New MDROs were found in 10% of all patients. Conclusions: Treatment of culture-negative sepsis with short-course antibiotics was not associated with worse outcomes in ICU patients. These findings warrant further investigation with a larger, prospective, multi-center study.

Overview of Pediatric Procalcitonin Testing Patterns in a Tertiary Care Children's Hospital.

The use of procalcitonin (PCT) has grown over the past decade with increasing reliance on the test to rule out bacterial infection. We retrospectively reviewed the medical records of children <18 years old hospitalized at a tertiary care children's hospital from 2017 to 2019 who had PCT testing performed during their admission. Of 4135 PCT levels collected on 1530 children, 982 (23.7%) were diagnostically low and 1993 (48.1%) were diagnostically elevated. Pediatric intensive care, with 6% of total hospital patients, obtained 41.4% of tests. Thirty-one (2%) patients had an average of 27 PCT levels per patient, accounting for 20% of all tests. Many children had symptoms for which testing is not indicated (eg, skin complaints). The differences in PCT testing by service, inappropriate patterns of repeat testing, and testing performed in patients for whom it is not indicated may identify targets for diagnostic stewardship.

Retrospective Comparison of Cefdinir, Cephalexin, and Sulfamethoxazole-Trimethoprim in the Treatment of Outpatient Pediatric Urinary Tract Infections.

This retrospective single-center study included children aged 2 months to 18 years who were prescribed an oral antibiotic for microbiologically confirmed urinary tract infection (UTI). The primary outcomes were re-encounter to the hospital, emergency department, or urgent care within 30 days and modification of the antibiotic regimen within 14 days. Development of Clostridioides difficile (C difficile) infection or new allergic reaction to the antibiotic prescribed was the secondary outcome. The sample included 2685 children. Rates of re-encounter were similar regardless of the initial antibiotic prescribed (P = .88), and patients who received cefdinir had a lower rate of medication changes (5%) compared with both cephalexin (14%) and sulfamethoxazole-trimethoprim (15%) (P ≤ .001). The most common reason for medication change was susceptibility interpretation. Given its low side-effect profile and narrow spectrum compared with the alternatives, cephalexin appears to be a reasonable choice as first-line therapy for the treatment of uncomplicated pediatric UTI.

Seroprevalence of Human T-Cell Lymphotropic Virus-1 in a Jamaican Antenatal Population and Assessment of Pooled Testing as a Cost Reduction Strategy for Implementation of Routine Antenatal Screening.

Mother to child transmission (MTCT) of human T-cell lymphotropic virus (HTLV)-1 is associated with increased risk of adult T-cell leukemia and can be unrecognized without routine antenatal screening. We assessed the seroprevalence of HTLV-1/2 among pregnant women attending The University Hospital of the West Indies Antenatal Clinic, 2019, and validated a cost-effective strategy to screen antenatal clinic attendees for HTLV-1/2. Residual antenatal samples from 370 women were tested for HTLV-1/2 by chemiluminescence microparticle immunoassay (CMIA). Six samples were confirmed HTLV-1 positive by Western blot (none for HTLV-2) for a prevalence of 1.62%. Four mother-child pairs were able to be recruited for HTLV testing of children, with two children testing HTLV-1/2 positive. Medical records of HTLV-1-infected women revealed that all women breastfed, indicating an unrecognized risk for HTLV MTCT. To assess whether pooling of samples as a cost-reduction strategy could be introduced, we pooled all antenatal samples received between November and December 2021 into 12 pools of eight samples/pool. Two pools were CMIA positive, and de-pooling of samples identified two CMIA-positive samples (one per pool), both confirmed as HTLV-1 by Western blot. These results indicate that HTLV-1 remains prevalent in pregnant Jamaican women and that sample pooling can be a cost-effective strategy to limit MTCT in Jamaica.

Management of Children with Reported Penicillin Allergies.

Penicillin allergy is the most commonly reported medication allergy. Reported allergy is associated with increased morbidity and mortality. Risk categorization tools can help determine the optimal testing strategies to delabel patients with reported allergy. Approaches to allergy removal include oral challenge in low-risk patients and skin testing in high-risk patients. Many different locations may be used to test for allergy, including ambulatory care clinics, inpatient units, and emergency departments. Interventions (eg, use of the electronic medical record) are needed to ensure that once the allergy is removed, this information is effectively transmitted to the patient and appropriate providers.

Double Take on Double Vision: Invasive Rhinosinusitis From Blastomyces dermatitidis in an Adolescent With Well-Controlled Diabetes.

Blastomyces dermatitidis is a fungus endemic to the Ohio and Mississippi river valley region and great lakes region. Exposure is typically associated with outdoor activities near streams, rivers, or moist soil. Pulmonary disease is the main manifestation, whereas dissemination is more frequently observed in immunosuppressed individuals. We herein report an uncommon case of B. dermatitidis causing invasive fungal sinusitis in a patient with well-controlled type 2 diabetes mellitus in the absence of conventional higher-risk environmental exposures. This case highlights the importance of a broad differential for invasive fungal infections in patients with diabetes, including those in endemic areas without classical exposures.