Emollients are readily available in prescription and over-the-counter products, and are commonly used in homes and healthcare facilities. These products are not harmful or flammable in isolation, but if they are combined with flames, such as the light of a cigarette, and fabric, they accelerate fires, resulting in burns and deaths. This article describes a Prevent Future Death (PFD) case report of a 74-year-old woman who succumbed to burns in the presence of paraffin-based emollient creams and a lighted match. We highlight the fire risks of such products and the need for greater awareness among the public and healthcare professionals.
Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid (RA) pharmacokinetics in pre-clinical neuroblastoma models. Here, we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance RA action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here, we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signalling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans.
Background: Deaths from opioids have increased in England and Wales, despite recognition of their harms. Coroners Prevention of Future Death reports (PFDs) provide important insights that may enable safer use and avert harms, yet these reports involving opioids have not been synthesised. We, therefore, aimed to identify opioid-related PFDs and explore concerns expressed by coroners to prevent future deaths. Methods: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022. These were obtained by web scraping the UKs Courts and Tribunals Judiciary website to create an openly available database: https://preventabledeathstracker.net/. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners and responses to such concerns. Findings: Opioids were involved in 219 deaths reported by coroners in PFDs (6% of all PFDs), equating to 4418 years of life lost (mean 32 years/person). Morphine (29%), methadone (23%), and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to NHS organisations (51%), but response rates were low overall (47%). Interpretation: Opioids could be used more safely and appropriately if coroners' concerns in PFDs were addressed by national organisations such as NHS bodies, government agencies, and policymakers, as well as individual prescribing clinicians.
AimsThe Oxford City and NE Oxon Adult Mental Health Team (AMHT) is an adult mental health team receiving referrals from GPs for most cases suspected to have a mental health illness requiring secondary mental health services’ input in Oxford city. In January 2020, the team was remodelled with care coordinators working in separate functions based on the duration AMHT support was required for, i.e. an assessment team and a treatment team, but with medics covering both functions of the team. This quality improvement project examines AMHT referrals over 2020/21, hypothesising a reduction in the proportion of inappropriate referrals following the remodelling compared to a 2018/19 pre-remodelling audit.MethodsThe project covers a total of 2803 referrals the team has received from 13/01/2020 to 12/01/2021. The outcomes measured included the number of inappropriate referrals returned to the GP, referrals only requiring a single assessment, the proportion of these referrals as university students in Oxford, and the diagnostic groupings of the referrals in students vs non-students. These outcomes were measured pre- and during the COVID-19 pandemic over 2020/21.ResultsA reduction in the total number of referrals to the team was noted over 2020/21 but this was compared to an 11 month audit in 2018/2019. During the study period, 19.5% (546/2803) of referrals were deemed inappropriate compared to 21% of referrals received in 2018/2019. Of 2803 referrals, 14.7% (97/658) were inappropriate pre-COVID-19 vs 20.9% (449/2145) during the pandemic. Of the total number of referrals, 32.9% were returned to the GP following a single assessment.The top 3 diagnostic categories in ‘non-students’ were mood/affective disorders (33.7%), anxiety/stress related disorders (17.2%), and neurodevelopmental disorders (7.8% total - ADHD was 3%). A significant increase in ADHD referrals and mood disorders amongst students compared to non-students is notable with the top 3 diagnostic categories for students being mood/affective (24.7%), neurodevelopmental disorders (19.5% - ADHD 17.7%), and anxiety/stress related disorders (13.4%). Students constituted 26% of the total number of referrals.It was notable that during the pandemic there was a higher proportion of inappropriate referrals.ConclusionOur project demonstrates a reduction in the proportion of inappropriate referrals sent to the AMHT following remodelling as compared to 2018/19. Further work is necessary to elucidate the contributing factors and reduce inappropriate referrals even further. An innovation is planned to automate the logging of referral outcomes to expedite a re-audit.
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