Defining a threshold above which an adult can be considered to frequently use ambulance services: a retrospective cross-sectional study of emergency calls to an ambulance service in England.

Objective: There is no empirical definition of adult frequent use of ambulance services. This study aimed to define a threshold, and utilise this to explore characteristics of people frequently using services. Methods: This was a retrospective cross-sectional study in a single ambulance service in England. Routinely collected, pseudo-anonymised call- and patient-level data were collected for two months (January and June 2019). Incidents, defined as independent episodes of care, were analysed using a zero-truncated Poisson regression model to determine a suitable frequent-use threshold, with comparisons subsequently made between frequent and non-frequent users. Results: A total of 101,356 incidents involving 83,994 patients were included in the analysis. Two potentially appropriate thresholds were identified: five incidents per month (A); and six incidents per month (B). Threshold A produced 3137 incidents from 205 patients, with five patients likely false-positive identifications. Threshold B produced 2217 incidents from 95 patients, with no false-positive identifications but 100 false-negatives compared to threshold A. Regardless of threshold, frequent users compared to non-frequent users had relatively reduced service use between 08:00 and 15:00, were younger and were more likely to receive lower-priority responses (all p < 0.001). We identified several chief complaints indicative of increased frequent use, including chest pain, psychiatric/suicide attempt and abdominal pains/problems. Conclusions: We suggest a threshold of five incidents per month, with recognition that a small number of patients may be incorrectly identified as using ambulance services frequently. The rationale for this choice is discussed. This threshold may be applicable in wider UK settings and could be used for the routine automated identification of people using ambulance services frequently. The identified characteristics can help inform interventions. Future research should examine applicability of this threshold in other UK ambulance services and countries where patterns and determinants of frequent ambulance use may differ.

Frequent callers to UK ambulance services in the COVID-19 pandemic: managing mental health, social isolation and loneliness.

OBJECTIVES: Patients who frequently call ambulance services are a vulnerable yet heterogeneous population with unmet multiple and complex physical health, mental health and/or social care needs. In this article, we report the challenges that the COVID-19 pandemic has introduced for ambulance services across the UK when managing frequent callers, and reflect on how existing systems and practices are adapting to support changing patient needs. METHODS: Data reported in this article comprise reflections from the frequent caller leads in each ambulance service in the UK. All data were provided between 23 April 2020 and 1 May 2020, shortly after the peak of the outbreak in the UK. A single anonymised case study is also reported to illustrate how the pandemic is affecting people's circumstances and contributing to frequent caller behaviour. RESULTS: Ambulance services are observing changes to the frequent caller population, with many new frequent callers due to health anxiety caused or exacerbated by the pandemic. Management of frequent callers is also changing, with multidisciplinary and multi-agency working becoming more challenging due to decreased access to external services, whether in social care or the community and voluntary sector, and the redeployment of ambulance service staff. There is also decreased face-to-face contact with frequent callers, meaning that opportunities to deliver person-centred care are reduced. However, the introduction or increased use of tele/video conferencing with other organisations has mitigated some of these challenges, and in some cases has improved engagement among external organisations. CONCLUSIONS: Health anxieties, lack of access to other health, social and community and voluntary sector services and exacerbations of social isolation and/or loneliness have reportedly contributed to changing behaviour among frequent callers. The COVID-19 pandemic has also affected how ambulance services have been able to manage frequent callers. Ambulance services should continue to engage with external organisations to aid the delivery of person-centred care, particularly organisations with experience in multiple complex needs such as mental health, social isolation and/or loneliness. Future research should examine the consequences of the pandemic for frequent users of ambulance services, and how these impact on the wider health and care community.

Maternally-inherited Grb10 reduces placental size and efficiency.

The control of foetal growth is poorly understood and yet it is critically important that at birth the body has attained appropriate size and proportions. Growth and survival of the mammalian foetus is dependent upon a functional placenta throughout most of gestation. A few genes are known that influence both foetal and placental growth and might therefore coordinate growth of the conceptus, including the imprinted Igf2 and Grb10 genes. Grb10 encodes a signalling adapter protein, is expressed predominantly from the maternally-inherited allele and acts to restrict foetal and placental growth. Here, we show that following disruption of the maternal allele in mice, the labyrinthine volume was increased in a manner consistent with a cell-autonomous function of Grb10 and the enlarged placenta was more efficient in supporting foetal growth. Thus, Grb10 is the first example of a gene that acts to limit placental size and efficiency. In addition, we found that females inheriting a mutant Grb10 allele from their mother had larger litters and smaller offspring than those inheriting a mutant allele from their father. This grandparental effect suggests Grb10 can influence reproductive strategy through the allocation of maternal resources such that offspring number is offset against size.

Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells.

The development of nontoxic natural agents with chemopreventive activity against colon cancer is the focus of investigation in many laboratories. Curcumin (feruylmethane), a natural plant product, possesses such chemopreventive activity, but the mechanisms by which it prevents cancer growth are not well understood. In the present study, we examined the mechanisms by which curcumin treatment affects the growth of colon cancer cells in vitro. Results showed that curcumin treatment causes p53- and p21-independent G(2)/M phase arrest and apoptosis in HCT-116(p53(+/+)), HCT-116(p53(-/-)) and HCT-116(p21(-/-)) cell lines. We further investigated the association of the beta-catenin-mediated c-Myc expression and the cell-cell adhesion pathways in curcumin-induced G(2)/M arrest and apoptosis in HCT-116 cells. Results described a caspase-3-mediated cleavage of beta-catenin, decreased transactivation of beta-catenin/Tcf-Lef, decreased promoter DNA binding activity of the beta-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a function of the G(2)/M phase arrest. The decreased transactivation of beta-catenin in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor Z-DEVD-fmk, even though the curcumin-induced cleavage of beta-catenin was blocked in Z-DEVD-fmk pretreated cells. The curcumin treatment also induced caspase-3-mediated degradation of cell-cell adhesion proteins beta-catenin, E-cadherin and APC, which were linked with apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our results suggest that curcumin treatment impairs both Wnt signaling and cell-cell adhesion pathways, resulting in G(2)/M phase arrest and apoptosis in HCT-116 cells.