Assessing Paracetamol Overdose in Children: Acceptability and Potential Market for a Non-Invasive Testing Device.

BackgroundAssessment of paracetamol overdose in children and teenagers in the emergency department (ED) requires blood, taken 4 hours post ingestion. A commercial partner developed transdermal paracetamol measuring technology. This work aims to understand the acceptability of such a device, and potential market size.MethodsA questionnaire study was undertaken with children and parents attending Alder Hey Children's Hospital, and healthcare professionals (HCP) involved in their care. A retrospective audit of paracetamol ingestion presenting to a paediatric ED was undertaken.ResultsOne hundred forty-three questionnaires were distributed, and 139 returned (response rate 97.2%), comprising 55 children, 52 parents and 32 HCP (recruited between August-October 2019). Overall device acceptability, assessed by favourability of appearance and willingness to wear was high, at 60.0% and 81.5% respectively. Concerns raised included bulky size and weight, and concern regarding the duration younger children would tolerate wearing the device. All groups, including children, ranked accuracy of results as the most important device feature and device comfort the least important. Parents prioritised avoidance of blood tests more than children. One hundred twenty-seven children presented to ED with paracetamol ingestion (September 2017-August 2018), with 57 (44.9%) categorised as accidental overdose. Overall, 106 (83.4%) required paracetamol concentration measuring, and 25 (19.7%) of these required treatment with N-acetylcysteine. Extrapolating nationally, over 7000 children will present with accidental overdose per annum in the UK.ConclusionAcceptability of a non-invasive paracetamol sensor was high in all groups, provided accuracy could be assured

Buffy the vampire slayer: what being Jewish has to do with it

This article examines the whiteness in the television series Buffy the Vampire Slayer. The author argues that the show’s overwhelming whiteness is a product of a generalized white anxiety about the numerical loss of white dominance across the United States and, in particular, in California. The article goes on to think through the role that Jewishness plays in the program, discussing the relationship between the apparently Anglo-American Buffy, played by a Jewish actor, and her sidekick, Willow, who is characterized as Jewish but is played by a non-Jewish actor. The evil master in the first series is given Nazi characteristics and the destruction that he wants to inflict carries connotations of the Holocaust. Structurally, Buffy is produced as the Jew who saves the United States from this demonic destruction. In this traumatic renarrativising, the Holocaust comes to stand for the white-experienced crisis of the loss of white supremacy in the United States. With this reading we can begin to understand the show’s popularity among early adult, predominantly white Americans

Improving pregnancy outcomes in humans through studies in sheep

Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A Cross-sectional Comparison of Delay Discounting in Smokers & Non-smokers with Schizophrenia and Respective Control Comparisons

Background: Schizophrenia is associated with deficits in decision-making. Aim: To determine the effects of smoking status on delay discounting in schizophrenia in comparison to non-psychiatric controls. Method: Cross-sectional comparison of delay discounting across smoking and psychiatric status. Hypotheses: Individuals with schizophrenia were hypothesized to have higher rates of delay discounting than controls; Non-smokers with schizophrenia would have higher rates of delay discounting than smokers. Control smokers would discount future rewards more than non-smokers. Results: No significant differences in delay discounting were observed between psychiatric groups. Smokers with schizophrenia exhibited more delay discounting than non-smokers. Within the psychiatric group, former smokers discount rates were similar to current smokers. Conclusion: Delay discounting deficits in schizophrenia and modulation by cigarette smoking were not supported; our pattern of results in schizophrenia does suggest that deficits in delay discounting in these patients appears to be a trait rather than a state-dependent phenomenon.MAS

A potential psychological mechanism linking disaster-related prenatal maternal stress with child cognitive and motor development at 16 months: the QF2011 Queensland flood study

Fetal exposure to prenatal maternal stress can have lifelong consequences, with different types of maternal stress associated with different areas of child development. Fewer studies have focused on motor skills, even though they are strongly predictive of later development across a range of domains. Research on mechanisms of transmission has identified biological cascades of stress reactions, yet links between psychological stress reactions are rarely studied. This study investigates the relationship between different aspects of disaster-related prenatal maternal stress and child cognitive and motor development, and proposes a cascade of stress reactions as a potential mechanism of transmission. Mothers in the Queensland Flood Study (QF2011) exposed to a major flood during pregnancy completed questionnaires assessing flood exposure, symptoms of peritraumatic distress, dissociation, and posttraumatic stress (PTSD), and cognitive appraisal of the overall flood consequences. At 16 months post-partum, children's (N = 145) cognitive and motor development was assessed using the Bayley-III. Flood exposure predicted child cognitive development and maternal PTSD symptoms and negative cognitive appraisal were significantly negatively related to child motor development, with all relationships moderated by timing of exposure. Together, a cascade of stress reactions linked maternal flood exposure to poorer fine motor development. These findings suggest that the way stress reactions operate together is as important as the way they operate in isolation, and identifies a potential psychological mechanism of transmission for the effects of prenatal stress. Results have implications for conceptualizing prenatal stress research and optimizing child development in the wake of natural disasters

sj-docx-1-bec-10.1177_11795972221140108 – Supplemental material for Assessing Paracetamol Overdose in Children: Acceptability and Potential Market for a Non-Invasive Testing Device

Supplemental material, sj-docx-1-bec-10.1177_11795972221140108 for Assessing Paracetamol Overdose in Children: Acceptability and Potential Market for a Non-Invasive Testing Device by Debora Freitas, Christopher Parry, Gabrielle Seddon, Jana Lemke, James Moss, Neville Freeman, Julie Grice and Daniel B Hawcutt in Biomedical Engineering and Computational Biology</p