Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) in pediatric patients with cancer can cause severe infections, and prompt antibiotics are warranted. Extrapolated from other populations, a time-to-antibiotic (TTA) metric of <60 minutes after medical center presentation was established, with compliance data factoring into pediatric oncology program national rankings. METHODS: All FN episodes occurring at Vanderbilt Children's Hospital (2007-February 2022) and a sample of episodes from Colorado Children's Hospital (2012-2019) were abstracted, capturing TTA and clinical outcomes including major complications (intensive care unit [ICU] admission, vasopressors, intubation, or infection-related mortality). Odds ratios (ORs) were adjusted for age, treatment center, absolute neutrophil count, hypotension presence, stem-cell transplant status, and central line type. RESULTS: A total of 2,349 episodes were identified from Vanderbilt (1,920) and Colorado (429). Only 0.6% (n = 14) episodes required immediate ICU management, with a median TTA of 28 minutes (IQR, 20-37). For the remaining patients, the median TTA was 56 minutes (IQR, 37-90), and 54.3% received antibiotics in <60 minutes. There were no significant associations between TTA (<60 or ≥60 minutes) and major complications (adjusted OR, 0.99 [95% CI, 0.62 to 1.59]; P = .98), and a TTA ≥60 minutes was not associated with any type of complication. Similarly, TTA, when evaluated as a continuous variable, was not associated with a major (OR, 0.99 [95% CI, 0.94 to 1.04]; P = .69) nor any other complication in adjusted analysis. CONCLUSION: There is no clear evidence that a reduced TTA improves clinical outcomes in pediatric oncology FN and thus it should not be used as a primary quality measure.

An Evaluation of the P300 Brain-Computer Interface, EyeLink Board, and Eye-Tracking Camera as Augmentative and Alternative Communication Devices.

PURPOSE: Augmentative and alternative communication (AAC) systems are important to support communication for individuals with complex communication needs. A recent addition to AAC system options is the brain-computer interface (BCI). This study aimed to compare the clinical application of the P300 speller BCI with two more common AAC systems, the EyeLink board, and an eye-tracking camera. METHOD: Ten participants without communication impairment (18-35 years of age) used each of the three AAC systems to spell three-letter words in one session. Accuracy and speed of letter selection were measured, and questionnaires were administered to evaluate usability, cognitive workload, and user preferences. RESULTS: The results showed that the BCI was significantly less accurate, slower, and with lower usability and higher cognitive workload compared to the eye-tracking camera and EyeLink board. Participants rated the eye-tracking camera as the most favorable AAC system on all measures. CONCLUSIONS: The results demonstrated that while the P300 speller BCI was usable by most participants, it did not function as well as the eye-tracking camera and EyeLink board. The clinical use of the BCI is, therefore, currently difficult to justify for most individuals, particularly when considering the substantial cost and setup resourcing needed. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21291384.

A "step too far" or "perfect sense"? A qualitative study of British adults' views on mandating COVID-19 vaccination and vaccine passports.

BACKGROUND: Debate is ongoing about mandating COVID-19 vaccination to maximise uptake. Policymakers must consider whether to mandate, for how long, and in which contexts, taking into account not only legal and ethical questions but also public opinion. Implementing mandates among populations who oppose them could be counterproductive. METHODS: Qualitative telephone interviews (Feb-May 2021) with British adults explored views on vaccine passports and mandatory vaccination. Participants (n = 50) were purposively selected from respondents to a probability-based national survey of attitudes to COVID-19 vaccination, to include those expressing vaccine-hesitancy. Data were analysed thematically. FINDINGS: Six themes were identified in participants' narratives concerning mandates: (i) mandates are a necessary and proportionate response for some occupations to protect the vulnerable and facilitate the resumption of free movement; (ii) mandates undermine autonomy and choice; (iii) mandates represent an over-reach of state power; (iv) mandates could potentially create 'vaccine apartheid'; (v) the importance of context and framing; and (vi) mandates present considerable feasibility challenges. Those refusing vaccination tended to argue strongly against mandates. However, those in favour of vaccination also expressed concerns about freedom of choice, state coercion and social divisiveness. DISCUSSION: To our knowledge, this is the first in-depth UK study of public views on COVID-19 vaccine mandates. It does not assess support for different mandates but explores emotions, principles and reasoning underpinning views. Our data suggest that debate around mandates can arouse strong concerns and could entrench scepticism. Policymakers should proceed with caution. While surveys can provide snapshots of opinion on mandates, views are complex and further consultation is needed regarding specific scenarios.

Increasing confidence in waiving dermal toxicity studies: A comparison of oral and dermal acute data with alternative approaches for agrochemicals and products.

The refinement of OECD 402 study design and criteria under which the study can be waived has been welcomed in some regulatory regions but met with uncertainty in others. To address these human safety concerns, previously available in vivo acute oral and acute dermal toxicity data was evaluated from a total of 597 agrochemical active ingredients and products. It was identified that all active ingredients and 99.6% of products had an acute dermal classification equal to or less toxic than their acute oral classification, confirming that waiving the acute dermal study and basing the outcome on the acute oral toxicity result has no impact on human health assessment. Additionally, automated Acute Toxicity Estimate (ATE) calculations were conducted on 440 products to evaluate if the predicted dermal toxicity resulted in the same in vivo classification. 93% of ATE predictions provided excellent correlation to the in vivo result and 6.4% resulted in a more conservative prediction. It is therefore clear that the results of this investigation, should remove any regulatory concerns and that OECD 402 can be confidently eliminated in its entirety from testing requirements globally.

Comparison of the predictive nature of the Genomic Allergen Rapid Detection (GARD) assay with mammalian assays in determining the skin sensitisation potential of agrochemical active ingredients.

Alternatives to mammalian testing are highly desirable to predict the skin sensitisation potential of agrochemical active ingredients (AI). The GARD assay, a stimulated, dendritic cell-like, cell line measuring genomic signatures, was evaluated using twelve AIs (seven sensitisers and five non-sensitisers) and the results compared with historical results from guinea pig or local lymph node assay (LLNA) studies. Initial GARD results suggested 11/12 AIs were sensitisers and six concurred with mammalian data. Conformal predictions changed one AI to a non-sensitiser. An AI identified as non-sensitising in the GARD assay was considered a potent sensitiser in the LLNA. In total 7/12 GARD results corresponded with mammalian data. AI chemistries might not be comparable to the GARD training set in terms of applicability domains. Whilst the GARD assay can replace mammalian tests for skin sensitisation evaluation for compounds including cosmetic ingredients, further work in agrochemical chemistries is needed for this assay to be a viable replacement to animal testing. The work conducted here is, however, considered exploratory research and the methodology needs further development to be validated for agrochemicals. Mammalian and other alternative assays for regulatory safety assessments of AIs must provide confidence to assign the appropriate classification for human health protection.

Point-of-care echocardiographic screening for left-sided valve heart disease: high yield and affordable cost in an elderly cohort recruited in primary practice.

BACKGROUND: Data about the epidemiology of valvular heart disease (VHD) in the elderly is scarce. Hand-held ultrasound devices (HUDs) enable point-of-care ultrasound scanning (POCUS) but their use in an elderly population has not been reported for VHD screening in primary practice. METHODS: One hundred consecutive subjects aged >70 years without a VHD diagnosis had 2D and colour Doppler POCUS by an accredited sonographer, using a contemporary HUD (Vscan), in a primary practice setting. Patients with left-sided valve pathology identified by Vscan were referred for formal echo in the local tertiary cardiac centre. RESULTS: Mean age (s.d.) was 79.08 (3.74) years (72-92 years); 61 female. By Vscan, we found five patients with ≥moderate aortic stenosis (AS), eight with ≥moderate mitral regurgitation (MR) and none with ≥moderate aortic regurgitation. In the AS and MR groups each, one patient had valve intervention following from the initial diagnosis by Vscan, two and one respectively are under follow-up in the valve clinic, while two and four respectively refused TTE or follow-up. Two patients with moderate MR by Vscan had mild and mild/moderate MR respectively by TTE and were discharged. Total cost for scanning 100 patients was $18,201 - i.e. $182/patient. CONCLUSIONS: Screening with a hand-held scanner (Vscan), we identified 5/100 elderly subjects who needed valve replacement or follow-up in valve clinic, at a cost of $182/patient. These findings have potential significance for the allocation of resources in the context of an ageing population.

Feasibility of Postmortem Imaging Assessment of Brain: Liver Volume Ratios with Pathological Validation.

INTRODUCTION: Organ volumes at postmortem magnetic resonance imaging (PMMR) should reflect autopsy organ weights, and thus brain:liver volume ratios on imaging could be a surrogate for weight volume ratios at autopsy to indicate fetal growth restriction (FGR). This study aims to determine whether imaging-based organ volume ratios can replace autopsy organ weight ratios. Materials and Meth ods: An unselected cohort of perinatal deaths underwent PMMR prior to autopsy. Semiautomated brain and liver volumes were compared to autopsy organ weights and ratios. Ratios were compared using Bland-Altman plots, and intra- and interobserver variability was assessed. RESULTS: A total 49 fetuses (25 male, 51%) at 17-42 weeks gestation were -assessed. There was a reasonable correlation between autopsy-derived brain:liver weight ratios (AB:LwR) and imaging-derived brain:liver volume ratios (IB:LvR; r = 0.8). The mean difference between AB:LwR and IB:LvR was +0.7 (95% limits of agreement range -1.5 to +2.9). In a small subset where FGR was present, the optimal IB:LvR ≥5.5 gave 83.3% sensitivity and 86.0% specificity for diagnosis. There was acceptable agreement within readers (mean difference in IB:LvRs 0.77 ± 2.21) and between readers -0.36 ± 0.68. CONCLUSION: IB:LvR provides a surrogate evaluation of AB:LwRs, and may be used as a marker of FGR where autopsy is declined.

Paediatric bowel ultrasound in inflammatory bowel disease.

Ultrasound has long been favoured as first line when imaging children, primarily due to it being a non-invasive, relatively low cost, easily accessible modality. The many advantages of ultrasound evaluation in paediatric inflammatory bowel disease (IBD) vastly outweighs its limitations in both initial assessment and long term follow up. High frequency ultrasound provides excellent spatial resolution, and Doppler evaluation and compression sonography aids in providing real-time dynamic assessment in IBD where other modalities cannot. This paper outlines our ultrasound technique to maximise image quality and diagnostic accuracy, describes the imaging findings in paediatric IBD, and explores the advantages and limitations that ultrasound offers. We aim to illustrate to the reader that ultrasound is an invaluable imaging tool and should be the first line modality when imaging IBD in the paediatric patient.