A Penicillin Allergy Stewardship Team to Address Unconfirmed Pediatric Penicillin Allergies in Houston, TX.

BACKGROUND: Penicillin (PCN) allergy labels are common and limit use of first-line antibiotics for common pediatric bacterial infections. Improving access to PCN allergy evaluations is a priority for allergy & immunology (A&I) and infectious diseases (ID) programs. OBJECTIVE: The objective of this study was to increase the number of completed PCN allergy evaluations from six to twenty-four per month from Jan 2022-Dec 2023. METHODS: A collaborative PCN allergy stewardship team was established in the A&I and ID divisions at Texas Children's Hospital. Telemedicine evaluations and, when clinically indicated, in-person PCN allergy evaluations were conducted from Jan-Dec 2023. Plan-do-study-act cycles were conducted to increase awareness about the clinics. The primary outcome measure was the average number of monthly completed PCN allergy evaluations. RESULTS: The average number of completed PCN allergy evaluations increased from six to 19 per month. Children were seen rapidly in the ID telemedicine clinic (20 versus 62 days, p<0.001), and 428/627 (68%) children who required in-person challenge were scheduled for their in-person evaluation. Of the 211 children de-labeled, 71 (33.6%) were subsequently diagnosed with a bacterial infection requiring penicillin during the study period. CONCLUSION: A collaborative penicillin allergy stewardship team consisting of ID and A&I specialists increased the number of completed penicillin allergy evaluations three-fold. ID telemedicine services allowed prompt access to care, and most children were de-labeled and subsequently able to receive penicillin antibiotics for bacterial respiratory tract infections. Future work should explore ways to minimize barriers to penicillin allergy evaluations and further expand testing services in other primary care settings.

Eosinophilic Meningitis: Eleven-Year Experience at Texas Children's Hospital.

Eosinophilic meningitis can be caused by various etiologies and is reported mostly in tropical climates. The diagnosis is rare in the continental US, presenting challenges for management. Following a case of pediatric eosinophilic meningitis, we reviewed our 11-year experience with this diagnosis at a large US children's hospital.

Necrotizing enterovirus myositis in a pediatric renal transplant recipient.

BACKGROUND: Enteroviruses can cause severe infections, including viral myocarditis, meningitis, acute flaccid myelitis, and viral myositis. METHODS/RESULTS: We report a 3-year-old female renal transplant recipient who presented to a tertiary care hospital with elevated serum liver aminotransferases and subsequently developed proximal muscle pain, weakness, and respiratory distress during the first week of hospitalization. Imaging of the lower extremities revealed diffuse myositis of the proximal thigh and pelvic muscles. A muscle biopsy was obtained and revealed necrotizing myositis with immunostaining positive for enterovirus, consistent with a diagnosis of enterovirus necrotizing myositis. She had complete resolution of symptoms with steroids, intravenous immune globulin, reduced tacrolimus dose, and physical therapy. CONCLUSIONS: Enterovirus myositis should be included in the differential diagnosis for necrotizing myositis following renal transplantation in children.

Therapeutic efficacy of N-acetylcysteine and zinc sulphate against di-(2-ethylhexyl) phthalate-induced testicular oxido-nitrergic stress in male Wistar rat.

The therapeutic efficacy of N-acetylcysteine (NAC) and zinc sulphate on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular oxido-nitrergic stress in rats was investigated in 36 male Wistar rats (170 ± 10 g) randomly assigned into one of six groups (n = 6). Group 1 (control) received 2.5 ml/kg of distilled water for 42 days, while group 2 (vehicle) received 2.5 ml/kg of corn oil for 42 days. Groups 3,4,5, and 6 were administered DEHP (750 mg/kg/day) for 21 days, after which groups 4, 5, and 6 received zinc sulphate (0.5 mg/kg/day), NAC (100 mg/kg/day), and zinc sulphate (0.5 mg/kg/day) + NAC (100 mg/kg/day) for an additional 21 days respectively. After the experimental period, the animals were euthanized by light thiopental sodium, and their testes were carefully dissected out for histological and biochemical assays. The result shows a significant alteration in testicular levels of malondialdehyde, nitric oxide, antioxidant enzymes, total antioxidant capacity, sulphydryl levels, dehydrogenases and testicular architecture following the administration of DEHP. These effects were reversed by coadministration of NAC and zinc sulphate in the study. We therefore concluded that the combined effects of NAC and ZnSO4 effectively improved testicular antioxidant status and reduced testicular nitregic stress, thus improving testicular architecture and functions.

The Green Light on Buying a Car: How Consumer Decision-Making Interacts with Environmental Attributes in the New Vehicle Purchase Process.

Although it is commonly understood that the average U.S. new vehicle buyer ranks price and safety above environmental attributes, a stated ranking of one shopping criterion above another is not necessarily maintained when consumers make an actual purchase decision. In fact, the distribution of shopping criteria rankings is not well understood, and it is unclear how rankings translate to the attributes of purchased vehicles. This raises several related questions: What is the distribution of shopping criteria rankings across the U.S. and how do they differ among demographic groups and purchasers of different vehicle fuel types or body styles?How do consumers weigh their purchase criteria?How does the environmental impact of a vehicle rank as a purchase criterion for U.S. new vehicle buyers, and its importance differ among gender, age, or income groups?Do purchase criteria differ for consumers who state that they value the environment?Is a consumer's shopping criteria ranking of environmental attributes reflected in the vehicles they consider and ultimately purchase? We explore these issues using data from an extensive survey of new vehicle buyers in 2014, 2015, and 2016 (approximately 250,000 respondents per year). We broadly find the environmental criterion outranked by preference for safety and performance, but different patterns emerge across groups defined by household income, purchased vehicle fuel type, and other measures of respondent attitude toward the environment. Stated preferences for environmental attributes align with higher fuel economy and greater likelihood of electric or hybrid fuel type within considered and purchased vehicles.

Publication rates of hematology/oncology abstracts presented at major pharmacy association meetings.

INTRODUCTION: Professional conferences are where research findings are initially presented. Studies suggest many research ideas presented at conferences are never published. Previous studies have demonstrated that the full publication rate of abstracts presented at pharmacy meetings is approximately 20%. The objective of this study was to determine the full publication rate of hematology/oncology abstracts presented at major pharmacy organization annual meetings. METHODS: A systematic search of PubMed and Google Scholar was performed. Publication status was evaluated for hematology/oncology abstracts presented at annual meetings for the following organizations: American College of Clinical Pharmacy Annual Meeting, American Society of Health-System Pharmacists Midyear Clinical Meeting, Hematology/Oncology Pharmacy Association Annual Meeting, and International Society of Oncology Pharmacy Practitioners Annual Meeting. Data collected included the meeting of abstract presentation, number of authors, abstract study type, country of origin, journal of publication, and type of publication. Abstracts presented as trainee research were excluded. RESULTS: Of 451 oncology abstracts evaluated, the most common topic categories included pharmacotherapy (n = 244; 54.1%), clinical pharmacy practice (n = 84; 18.6%), and operational/compounding (n = 69; 15.3%). The overall publication rate was 17.5% (n = 79). Abstracts were published as full manuscripts over a spread of 48 different journals. Factors associated with full publication included abstracts with more than 5 authors (OR 3.86, 95% CI 2.32-6.43; p < 0.0001) and abstracts presented at oncology-focused pharmacy meetings (OR 2.92, 95% CI 1.49-5.72; p = 0.0018). CONCLUSION: This study showed an overall publication rate of 17.5% for abstracts presented at pharmacy meetings, consistent with prior studies.

Unconfirmed penicillin allergy labels in the paediatric outpatient setting: A call for research and quality improvement initiatives.

Over the last 10 years, the electronic medical record has redefined medical documentation, and physicians rely on accurate records to make clinical decisions. Penicillin allergy labels (PALs) are important pieces of the medical history that guide physicians in selecting specific antibiotic classes for the treatment of infectious diseases. However, most children labelled as penicillin-allergic do not have an IgE-mediated (immediate) allergic reaction to penicillin or its derivatives. In the absence of confirmatory penicillin allergy testing or additional history, these children receive alternative, often broad-spectrum and second-line, antibiotics. Addressing unconfirmed PALs requires an understanding of how and why labels get added to the electronic medical record. This viewpoint highlights the knowledge gaps in paediatric outpatient penicillin allergy labelling and proposes an acronym ('LABEL') that primary care providers and antimicrobial stewards can utilise when designing initiatives to address unconfirmed PALs in the community.

Select and resequence reveals relative fitness of bacteria in symbiotic and free-living environments.

Assays to accurately estimate relative fitness of bacteria growing in multistrain communities can advance our understanding of how selection shapes diversity within a lineage. Here, we present a variant of the "evolve and resequence" approach both to estimate relative fitness and to identify genetic variants responsible for fitness variation of symbiotic bacteria in free-living and host environments. We demonstrate the utility of this approach by characterizing selection by two plant hosts and in two free-living environments (sterilized soil and liquid media) acting on synthetic communities of the facultatively symbiotic bacterium Ensifer meliloti We find (i) selection that hosts exert on rhizobial communities depends on competition among strains, (ii) selection is stronger inside hosts than in either free-living environment, and (iii) a positive host-dependent relationship between relative strain fitness in multistrain communities and host benefits provided by strains in single-strain experiments. The greatest changes in allele frequencies in response to plant hosts are in genes associated with motility, regulation of nitrogen fixation, and host/rhizobia signaling. The approach we present provides a powerful complement to experimental evolution and forward genetic screens for characterizing selection in bacterial populations, identifying gene function, and surveying the functional importance of naturally occurring genomic variation.

Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy.

We synthesized a library of aminopyrazole analogs to systematically explore the hydrophobic pocket adjacent to the hinge region and the solvent exposed region of cyclin dependent kinases. Structure-activity relationship studies identified an optimal substitution for the hydrophobic pocket and analog 24 as a potent and selective CDK2/5 inhibitor.

Prevention of influenza by targeting host receptors using engineered proteins.

There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1-µg intranasal dose 7 d in advance of viral challenge. There also is sufficient virus replication to establish an immune response, potentially protecting the animal from future exposure to the virus. Furthermore, the biologics appear to stimulate inflammatory mediators, and this stimulation may contribute to their protective ability. Our results suggest that this host-targeted approach could provide a front-line prophylactic that has the potential to protect against any current and future influenza virus and possibly against other respiratory pathogens that use sialic acid as a receptor.

Transport Function of Rice Amino Acid Permeases (AAPs).

The transport function of four rice (Oryza sativa) amino acid permeases (AAPs), OsAAP1 (Os07g04180), OsAAP3 (Os06g36180), OsAAP7 (Os05g34980) and OsAAP16 (Os12g08090), was analyzed by expression in Xenopus laevis oocytes and electrophysiology. OsAAP1, OsAAP7 and OsAAP16 functioned, similarly to Arabidopsis AAPs, as general amino acid permeases. OsAAP3 had a distinct substrate specificity compared with other rice or Arabidopsis AAPs. OsAAP3 transported the basic amino acids lysine and arginine well but selected against aromatic amino acids. The transport of basic amino acids was further analyzed for OsAAP1 and OsAAP3, and the results support the transport of both neutral and positively charged forms of basic amino acids by the rice AAPs. Cellular localization using the tandem enhanced green fluorescent protein (EGFP)-red fluorescent protein (RFP) reporter pHusion showed that OsAAP1 and OsAAP3 localized to the plasma membrane after transient expression in onion epidermal cells or stable expression in Arabidopsis.

Sialic acid-binding protein Sp2CBMTD protects mice against lethal challenge with emerging influenza A (H7N9) virus.

Compounds that target the cellular factors essential for influenza virus replication represent an innovative approach to antiviral therapy. Sp2CBMTD is a genetically engineered multivalent protein that masks sialic acid-containing cellular receptors on the respiratory epithelium, which are recognized by influenza viruses. Here, we evaluated the antiviral potential of Sp2CBMTD against lethal infection in mice with an emerging A/Anhui/1/2013 (H7N9) influenza virus and addressed the mechanistic basis of its activity in vivo. Sp2CBMTD was administered to mice intranasally as a single or repeated dose (0.1, 1, 10, or 100 µg) before (day -7, -3, and/or -1) or after (6 or 24 h) H7N9 virus inoculation. A single Sp2CBMTD dose (10 or 100 µg) protected 80% to 100% of the mice when administered 7 days before the H7N9 lethal challenge. Repeated Sp2CBMTD administration conferred the highest protection, resulting in 100% survival of the mice even at the lowest dose tested (0.1 µg). When treatment began 24 h after exposure to the H7N9 virus, a single administration of 100 µg of Sp2CBMTD protected 40% of the mice from death. The administration of Sp2CBMTD induced the pulmonary expression of proinflammatory mediators (interleukin-6 [IL-6], IL-1ß, RANTES, monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], and inducible protein [IP-10]) and recruited neutrophils to the respiratory tract before H7N9 virus infection, which resulted in less pronounced inflammation and rapid virus clearance from mouse lungs. Sp2CBMTD administration did not affect the virus-specific adaptive immune response, which was sufficient to protect against reinfection with a higher dose of homologous H7N9 virus or heterologous H5N1 virus. Thus, Sp2CBMTD was effective in preventing H7N9 infections in a lethal mouse model and holds promise as a prophylaxis option against zoonotic influenza viruses.

Innovation under cap-and-trade programs.

Policies incentivizing the private sector to reach its innovative potential in "clean" technologies are likely to play a key role in achieving climate stabilization. This article explores the relationship between innovation and cap-and-trade programs (CTPs)--the world's most prominent climate policy instrument--through empirical evidence drawn from successful CTPs for sulfur dioxide and nitrogen oxide control. The article shows that before trading began for these CTPs, analysts overestimated the value of allowances in a pattern suggestive of the frequent a priori overestimation of the compliance costs of regulation. When lower-than-expected allowance prices were observed, in part because of the unexpected range of abatement approaches used in the lead-up to trading, emissions sources chose to bank allowances in significant numbers and reassess abatement approaches going forward. In addition, commercially oriented inventive activity declined for emissions-reducing technologies with a wide range of costs and technical characteristics, dropping from peaks before the establishment of CTPs to nadirs a few years into trading. This finding is consistent with innovators deciding during trading that their research and development investments should be reduced, based on assessments of future market conditions under the relevant CTPs. The article concludes with a discussion of the results and their implications for innovation and climate policy.

Barred owls and landscape attributes influence territory occupancy of northern spotted owls.

We used multi-season occupancy analyses to model 2 fates of northern spotted owl territories in relation to habitat amount, habitat fragmentation, and the presence of barred owls in Washington State, USA, 1989-2005. Local colonization is the probability a territory unoccupied by a spotted owl in year i would be occupied in year i + 1, and local extinction is the probability a territory that was occupied by a spotted owl in year i would be unoccupied in year i + 1. We found a negative relationship between local extinction probability and amount of late-seral forest edge. We found a negative relationship between colonization probability and the number of late-seral forest patches (higher fragmentation), and a negative relationship between colonization probability and the amount of non-habitat within 600 m of a spotted owl territory center (Akaike weight = 0.59). The presence of barred owls was positively related to extinction probability and negatively related to detection probability of spotted owls. The negative relationship between presence of barred owls and detectability of spotted owls indicated that spotted owls could be modifying their calling behavior in the presence of barred owls. The positive relationship between barred owl detections and local extinction probability suggests that because of competition with barred owls, spotted owls are being displaced. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Women's experiences of the diagnostic journey in uterine adenomyosis: a scoping review protocol.

INTRODUCTION: Uterine adenomyosis is a benign gynaecological disease that causes physical and psychological problems, impacting on relationships. It is poorly understood and consequently may be diagnosed late. This protocol describes the process of conducting a systematic scoping review to retrieve and describe literature examining the daily experience and impact of living with uterine adenomyosis. It will explore the journey to diagnosis (and perceptions of what this process is like); identify the main concepts currently used in the literature and highlight gaps in knowledge for future research in relevant populations. METHODS AND ANALYSIS: Using the Joanna Briggs Institute methodology, the population-concept-context approach is used to form clear review questions. A three-phase search strategy will locate published and unpublished evidence from multiple sources. All articles reporting on the personal experiences of women diagnosed with uterine adenomyosis will be considered. Findings from qualitative, quantitative and mixed-method study designs from all settings will be included, not limited by geography but restricted to English. Documents will be screened by the primary researcher, supported by university supervisors. Search outputs will be presented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram. No formal quality appraisal will be conducted. Review findings will be descriptively collated and reported consistent with the Scoping Review Extension of the PRISMA checklist. Patient and public involvement engagement reflected a positive response for the project that this protocol supports. ETHICS AND DISSEMINATION: As primary data will not be collected, formal ethical approval is not required. Prepared as part of a professional doctorate thesis, the findings of this study will be disseminated via peer-reviewed publications, conference presentations, support groups and social media networks.

The epidemiology of cephalosporin allergy labels in pediatric primary care.

Background: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting. Methods: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis media were compared in children with and without cephalosporin allergies. Results: 334,465 children comprised the birth cohort and 2,877 (0.9%) were labeled as cephalosporin allergic during the study period at a median age of 1.6 years. Third-generation cephalosporins were the most common class of cephalosporin allergy (83.0%). Cephalosporin allergy labels were more common in children with penicillin allergy labels than those without (5.8% vs. 0.6%). Other factors associated with a cephalosporin allergy label included white race, private insurance, presence of a chronic condition, and increased health care utilization. Children with third-generation cephalosporin allergy labels received more amoxicillin/clavulanate (28.8% vs. 10.2%) and macrolides (10.4% vs. 1.9%) and less amoxicillin (55.8% vs. 70.9%) for treatment of acute otitis media than non-allergic peers p < 0.001. Conclusions: One in 100 children is labeled as cephalosporin allergic, and these children receive different antibiotics for the treatment of acute otitis media compared to non-allergic peers.

Impact of Penicillin Allergy Labels on Children Treated for Outpatient Respiratory Infections.

BACKGROUND: Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI). METHODS: A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, adjusting for potential confounders. RESULTS: Antibiotics were prescribed for 663,473 non-recurrent RTIs among 200,977 children. Children with a PAL (5% of cohort) were more likely than non-allergic children to receive broad-spectrum antibiotics (adjusted relative risk (aRR) 3.24, 95% CI 3.22-3.26) and second-line antibiotics (aRR 4.87, 95% CI 4.83, 4.89). Compared to non-allergic children receiving first-line antibiotics, children with a PAL were more likely to return with adverse drug events (aRR 1.28, 95% CI 1.18-1.39). There was no difference in treatment failure between groups (aRR 0.95, 95% CI 0.90-1.00). CONCLUSIONS: PALs lead to higher rates of broad-spectrum and second-line antibiotic prescribing in children treated for RTIs in primary care and contribute to unnecessary healthcare utilization through increased adverse events. Given the frequency of PALs, efforts to prevent inappropriate penicillin allergy labeling and promote de-labeling of existing inaccurate allergy labels may improve care of children treated for common bacterial infections.