Economic modelling of providing ‘spare’ adrenaline autoinjectors to all schools to improve the management of anaphylaxis

\ua9 Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.Objective To analyse NHS health datasets to estimate the cost of providing emergency adrenaline [epinephrine] autoinjectors (AAIs) to school pupils on a named-patient basis to leave on school premises versus providing ‘spare’ AAIs to schools which can be used for any school pupil. Design Retrospective cohort study. Setting English primary electronic health data from the Clinical Practice Research Datalink (CPRD) and English prescriptions data from the NHS Business Services Authority. Participants School-aged children in England. Main outcome measures (1) Proportion of school children with food allergy prescribed AAI; (2) cost of providing more than two AAIs to individual pupils mapped to integrated care boards (ICBs) in England compared with the cost of providing four spare AAIs to every school for the academic year 2023/24. Results 44% of school-aged children in the CPRD had at least one AAI prescription and only 34% had repeat AAIs prescribed. In pupils with previous anaphylaxis, rates were 59% and 44%, respectively. During the academic year 2023/24, 63% of pupils were dispensed more than two AAIs at an estimated cost of over \ua39 million. The estimated cost of providing spare AAIs to every school was \ua34.5 million. If spare AAIs were to replace the supply of named-patient AAIs exclusively to leave on school premises, this would represent a potential cost-saving of at least \ua34.6 million or 25% of the total national expenditure for AAIs. Conclusions Under half of children at risk of anaphylaxis are prescribed AAIs. Providing spare AAIs to all schools (at no cost to the school) would be a cost-neutral strategy for the vast majority of ICBs and one that is likely to improve emergency access to AAIs and therefore safety

Adrenaline Auto-Injector Prescribing in Primary Care in England: An Analysis of Non-Standard Dosing

\ua9 2025 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.Introduction: The recommended first-line treatment for anaphylaxis in the community is intramuscular injection of adrenaline. The treatment is a standardised dose of either a 150 μg or a 300 μg adrenaline auto-injector (AAI) device depending upon the patient\u27s weight. Currently, no standardised mechanisms exist to transition patients onto the higher 300 μg dose when they reach 25–30 kg (depending upon the manufacturer). Methods: We undertook analysis of NHS prescriptions data dispensed in the community in England to identify rates of non-standard AAI dose prescribing. Non-standard prescribing is defined as patients who are likely to have exceeded the 25–30 kg threshold but still received a 150 μg dose. Data were limited to the most recent AAI prescription for an individual patient that occurred in the last 2 years (December 2022–2024). Patient weight at the time of prescribing was approximated using an age-to-weight correlation model. AAI recommended switching weights, based on device metadata, were compared to the patients\u27 approximated weight to identify non-standard prescribing. Statistical comparison between rates of non-standard prescribing and patient deprivation was computed using Kendall\u27s Tau correlation coefficient. A complementary analysis to identify patients who received a 300 μg dose but were likely under the 25–30 kg threshold was also carried out. Results: Overall, 46,999 patients were identified as having received a 150 μg strength injector in their most recent AAI prescription; of these, over 95% received two or more devices in line with national guidance. Estimates based on age for weight growth centiles show that between 9480 (20.2%) and at least 1747 (3.7%) of those prescribed a 150 μg autoinjector were likely to exceed the weight threshold for this dose. Using a Resuscitation Council UK guideline of age 6 years for switching to a 300 μg dose, the estimated proportion prescribed a non-standard AAI dose increases to 23,059 patients (49.1%). Estimated rates of non-standard AAI prescribing were found to be higher in areas of England with the most deprivation. Conservative estimates found only 67 children likely under 25 kg and 330 children likely under 30 kg who received a 300 μg dose. Conclusions: This analysis of community AAI prescriptions in England suggests that underdosing of AAI prescriptions in children and adults is not uncommon. Healthcare professionals with patients at risk of anaphylaxis should review whether patients prescribed AAI devices have the appropriate device for their weight

An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing

The authors would like to thank the support on this research by the CRISP Project (Combinatorial Responses In Stress Pathways) funded by the BBSRC (BB/F00513X/1) under the Systems Approaches to Biological Research (SABR) Initiative.Peer reviewedPublisher PD

Effects of peripheral nerve injury on parvalbumin expression in adult rat dorsal root ganglion neurons

Background: Parvalbumin (PV) is a calcium binding protein that identifies a subpopulation of proprioceptive dorsal root ganglion (DRG) neurons. Calcitonin gene-related peptide (CGRP) is also expressed in a high proportion of muscle afferents but its relationship to PV is unclear. Little is known of the phenotypic responses of muscle afferents to nerve injury. Sciatic nerve axotomy or L5 spinal nerve ligation and section (SNL) lesions were used to explore these issues in adult rats using immunocytochemistry. Results: In naive animals, the mean PV expression was 25 % of L4 or L5 dorsal root ganglion (DRG) neurons, and this was unchanged 2 weeks after sciatic nerve axotomy. Colocalization studies with the injury marker activating transcription factor 3 (ATF3) showed that approximately 24 % of PV neurons expressed ATF3 after sciatic nerve axotomy suggesting that PV may show a phenotypic switch from injured to uninjured neurons. This possibility was further assessed using the spinal nerve ligation (SNL) injury model where injured and uninjured neurons are located in different DRGs. Two weeks after L5 SNL there was no change in total PV staining and essentially all L5 PV neurons expressed ATF3. Additionally, there was no increase in PV-ir in the adjacent uninjured L4 DRG cells. Co-labelling of DRG neurons revealed that less than 2 % of PV neurons normally expressed CGRP and no colocalization was seen after injury. Conclusion: These experiments clearly show that axotomy does not produce down regulation of PV protein in the DRG. Moreover, this lack of change is not due to a phenotypic switch in PV immunoreactive (ir) neurons, or de novo expression of PV-ir in uninjured neurons after nerve injury. These results further illustrate differences that occur when muscle afferents are injured as compared to cutaneous afferents

Incidence of childhood leukaemia in the vicinity of nuclear sites in France, 1990–1998

Overall, 670 cases (O) of childhood leukaemia were diagnosed within 20 km of the 29 French nuclear installations between 1990 and 1998 compared to an expected number (E) of 729.09 cases (O/E=0.92, 95% confidence interval (CI)=[0.85-0.99]). Each of the four areas defined around the sites showed non significant deficits of cases (0-5 km: O=65, O/E=0.87, CI=[0.67-1.10]; 5-10 km: O=165, O/E=0.95, CI=[0.81-1.10]; 10-15 km: O=220, O/E=0.88, CI=[0.77-1.00]; 15-20 km: O=220, O/E=0.96, CI=[0.84-1.10]). There was no evidence of a trend in standardised incidence ratio with distance from the sites for all children or for any of the three age groups studied. Similar results were obtained when the start-up year of the electricity-generating nuclear sites and their electric nuclear power were taken into account. No evidence was found of a generally increased risk of childhood leukaemia around the 29 French nuclear sites under study during 1990-1998

BSACI guidance for the implementation of Palforzia\uae peanut oral immunotherapy in the United Kingdom: A Delphi consensus study

Clinical & Experimental Allergy\ua9 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.Background: Palforzia\uae enables the safe and effective desensitisation of children with peanut allergy. The treatment pathway requires multiple visits for dose escalation, up-dosing, monitoring of patients taking maintenance therapy and conversion onto daily real-world peanut consumption. The demand for peanut immunotherapy outstrips current National Health Service (NHS) capacity and requires services to develop a national consensus on how best to offer Palforzia\uae in a safe and equitable manner. We undertook a Delphi consensus exercise to determine guidance statements for the implementation of Palforzia\uae-based immunotherapy in the NHS. Methods: We undertook focus groups with children and young people who had received peanut immunotherapy to assess what was important for them and their carers. Common themes from patients formed the basis of creating draft statements. A panel of 18 multi-disciplinary professionals engaged in two rounds of anonymised voting to adapt the statements and score their importance. A final consensus workshop consolidated any variation in comments and scores to develop the final guidance statements. Results: The panel achieved consensus on 91% (29/32) of guidance statements, demonstrating strong consensus around pragmatic principles for assuring the integrity of consent, safety and conversion from Palforzia\uae to real-world peanut products. The greatest amount of feedback was generated from three broad issues; (i) whether eligibility assessment should include compulsory peanut challenges and whether these should be designed to assess the threshold at which patients react to peanut, (ii) the governance processes to best ensure that patients\u27 interests are prioritised and (iii) how to safely transition young people to other services, or discharge them, while they are taking daily peanut. Conclusions: This consensus highlights the urgent need for the NHS to increase capacity for undertaking diagnostic food challenges as well as developing Palforzia\uae immunotherapy pathways. The voting panel agreed that families of peanut allergic children should be made aware of immunotherapy, that eligibility assessment should include how co-morbid conditions are managed and that services should monitor for adverse effects. The finalised statements are now published online for clinical practice in the UK. These guidance statements will be adapted in the coming years as more evidence is published and as the international experience of peanut immunotherapy evolves

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains a Poor Prognostic Factor in Multiple Myeloma but Outcomes Have Improved Over Time

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (\u3c 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky \u3c 90, stage III, \u3e 1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time

Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26 = 12.62; p = 0.0002; SMIT2: F2,26 = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2 levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6 months of age, cerebellar SMIT2 levels were also significantly higher than cortical levels (p<0.05). Inositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding

A multi-omics machine learning classifier for outgrowth of cow\u27s milk allergy in children

\ua9 The Royal Society of Chemistry 2025.Cow’s milk protein allergy (CMA) is one of the most common food allergies in children worldwide. However, it is still not well understood why certain children outgrow their CMA and others do not. While there is increasing evidence for a link of CMA with the gut microbiome, it is still unclear how the gut microbiome and metabolome interact with the immune system. Integrating data from different omics platforms and clinical data can help to unravel these interactions. In this study, we integrate clinical, microbial, (meta)proteomics, immune and metabolomics data into machine learning (ML) classification, using multi-view learning by late integration. The aim is to group infants into those that outgrew their CMA and those that did not. The results show that integration of microbiome data with clinical, immune, (meta)proteomics and metabolomics data could considerably improve classification of infants on outgrowth of CMA, compared to only considering one type of data. Moreover, pathways previously linked to development of CMA could also be related to outgrowth of this allergy

MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified <it>MDM2 </it>gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy.</p> <p>Methods</p> <p>A panel of sarcoma cell lines with different <it>TP53 </it>and <it>MDM2 </it>status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined.</p> <p>Results</p> <p>Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type <it>TP53 </it>and amplified <it>MDM2</it>, or with Methotrexate in both <it>MDM2 </it>normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated <it>TP53</it>, but inhibited the effect of Methotrexate.</p> <p>Conclusion</p> <p>The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.</p