Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

AIMS: In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l(−1)’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. METHODS: Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. RESULTS: There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million). CONCLUSIONS: The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning

Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Background and purpose: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. Methods: This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point. Results: In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P &lt; 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P &lt; 0.0001) and haemorrhage volume &gt;60 mL (HR, 4.08, P &lt; 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. Conclusions: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Comics, crime, and the moral self : an interdisciplinary study of criminal identity

An ethical understanding of responsibility should entail a richly qualitative comprehension of the links between embodied, unique individuals and their lived realities of behaviour. Criminal responsibility theory broadly adheres to ‘rational choice’ models of the moral self which subsume individuals’ emotionally embodied dimensions under the general direction of their rational will and abstracts their behaviour from corporeal reality. Linking individuals with their behaviour based only on such understandings of ‘rational choice’ and abstract descriptions of behaviour overlooks the phenomenological dimensions of that behaviour and thus its moral significance as a lived experience. To overcome this ethical shortcoming, engagement with the aesthetic as an alternative discourse can help articulate the ‘excessive’ nature of lived reality and its relationship with ‘orthodox’ knowledge; fittingly, the comics form involves interaction of rational, non-rational, linguistic, and non-linguistic dimensions, modelling the limits of conceptual thought in relation to complex reality. Rational choice is predicated upon a split between a contextually embedded self and an abstractly autonomous self. Analysis of the graphic novel Watchmen contends that prioritisation of rational autonomy over sensual experience is symptomatic of a ‘rational surface’ that turns away from the indeterminate ‘chaos’ of complex reality (the unstructured universe), instead maintaining the power of rational and linguistic concepts to order the world. This ‘rational surface’ is maintained by masking that which threatens its stability: the chaos of the infinite difference of living individuals. These epistemological foundations are reconfigured, via Watchmen, enabling engagement beyond the ‘rational surface’ by accepting the generative potential of this living chaos and calling for models of criminal identity that are ‘restless’, acknowledging the unique, shifting nature of individuals, and not tending towards ‘complete’ or stable concepts of the self-as-responsible. As part of the aesthetic methodology of this reconfiguration, a radical extension of legal theory’s analytical canon is developed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Comics, crime, and the moral self : an interdisciplinary study of criminal identity

An ethical understanding of responsibility should entail a richly qualitative comprehension of the links between embodied, unique individuals and their lived realities of behaviour. Criminal responsibility theory broadly adheres to ‘rational choice’ models of the moral self which subsume individuals’ emotionally embodied dimensions under the general direction of their rational will and abstracts their behaviour from corporeal reality. Linking individuals with their behaviour based only on such understandings of ‘rational choice’ and abstract descriptions of behaviour overlooks the phenomenological dimensions of that behaviour and thus its moral significance as a lived experience. To overcome this ethical shortcoming, engagement with the aesthetic as an alternative discourse can help articulate the ‘excessive’ nature of lived reality and its relationship with ‘orthodox’ knowledge; fittingly, the comics form involves interaction of rational, non-rational, linguistic, and non-linguistic dimensions, modelling the limits of conceptual thought in relation to complex reality. Rational choice is predicated upon a split between a contextually embedded self and an abstractly autonomous self. Analysis of the graphic novel Watchmen contends that prioritisation of rational autonomy over sensual experience is symptomatic of a ‘rational surface’ that turns away from the indeterminate ‘chaos’ of complex reality (the unstructured universe), instead maintaining the power of rational and linguistic concepts to order the world. This ‘rational surface’ is maintained by masking that which threatens its stability: the chaos of the infinite difference of living individuals. These epistemological foundations are reconfigured, via Watchmen, enabling engagement beyond the ‘rational surface’ by accepting the generative potential of this living chaos and calling for models of criminal identity that are ‘restless’, acknowledging the unique, shifting nature of individuals, and not tending towards ‘complete’ or stable concepts of the self-as-responsible. As part of the aesthetic methodology of this reconfiguration, a radical extension of legal theory’s analytical canon is developed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Enhancing care for transgender and gender diverse survivors of intimate partner violence: an Ontario-wide survey examining health and social service providers’ learning needs

Objectives To better understand healthcare and social/community service providers’ learning needs associated with supporting transgender and gender diverse (trans) persons who have experienced intimate partner violence (IPV).Setting An online survey was distributed through the trans-LINK Network in Ontario, Canada.Respondents 163 of 225 healthcare and social/community service providers completed the survey (72.4% response rate) between November 2022 and February 2023.Main outcome measures Expertise, training, workplace practices and learning needs related to supporting trans survivors of IPV.Method Quantitative survey results were analysed descriptively and open-ended responses were organised thematically. In March 2022, survey results were shared with 33 stakeholders who helped define goals and objectives for an e-learning curriculum using Jamboard, data from which were collated and organised into themes.Results Most (66.3%) survey respondents described having provided professional support to trans survivors of IPV, but only one-third (38.0%) reported having received relevant training, and many of the trainings cited were in fact focused on other forms of violence or trans health generally. The majority reported a mid (44.9%) or low-mid (28.5%) level of expertise and almost unanimously agreed that they would benefit from (further) training (99.4%). The most commonly recommended goal/objective for a curriculum emerging from the stakeholder consultation was to facilitate collaboration, knowledge sharing and (safe) referrals among organisations.Conclusions The results of this study highlight the critical need for an IPV curriculum specific to trans survivors and responsive to the needs of providers. As no one profession can address this complex issue in isolation, it is important that the curriculum aims to facilitate collaboration across sectors. In the absence of appropriate training and referrals, practitioners may perpetuate harm when caring for trans survivors of IPV