Development and implementation of the Specialist Palliative Care in Aged Care (SPACE) Project across Queensland.

There is an urgent and unmet need for specialist palliative care services in residential aged care. The Specialist Palliative Care in Aged Care (SPACE) Project aimed to improve palliative and end-of-life care for older people living in residential aged care facilities in Queensland. A representative working group developed a series of service principles around palliative care practice in aged care (comprehensive resident-focused care, streamlined service, and capacity building). Funding was allocated by population to the health services in Queensland to adapt and implement models of care aligned with these principles. SPACE successfully implemented a variety of decentralised models of care across Queensland. The critical elements for the success of SPACE were the use of an expert working group to define the core innovation, networking and implementation support from the central project team and community of practice, and adaptable models of care led by local facilitators. Lessons learned from this real-world case study could be adopted to guide and ensure the successful implementation and sustainability of future complex interventions in healthcare settings, both nationally and internationally.

Health care professionals' experiences of dealing with cancer cachexia.

BACKGROUND: Cancer cachexia (CC) is a debilitating syndrome severely impacting patients' quality of life and survivorship. We aimed to investigate the health care professionals' (HCPs') experiences of dealing with CC. METHODS: Survey questions entailed definitions and guidelines, importance of CC management, clinician confidence and involvement, screening and assessment, interventions, psychosocial and food aspects. The online survey was disseminated through Australian and New Zealand palliative care, oncology, allied health and nursing organisations. Frequencies were reported using descriptive statistics accounting for response rates. Associations were examined between variables using Fisher's exact and Pearson's chi-square tests. RESULTS: Over 90% of the respondents (n = 192) were medical doctors or nurses. Over 85% of the respondents were not aware of any guidelines, with 83% considering ≥ 10% weight loss from baseline indicative of CC. CC management was considered important by 77% of HCPs, and 55% indicated that it was part of their clinical role to assess and treat CC. In contrast, 56% of respondents were not confident about managing CC, and 93% believed formal training in CC would benefit their clinical practice. Although formal screening tools were generally not used (79%), 75% of respondents asked patients about specific symptoms. Antiemetics (80%) and nutritional counselling (86%) were most prescribed or recommended interventions, respectively. CONCLUSION: This study underlines the deficiencies in knowledge and training of CC which has implications for patients' function, well-being and survival. HCP training and a structured approach to CC management is advocated for optimal and continued patient care.

Cyclizine pharmacovigilance in hospice/palliative care: net effects for nausea or vomiting.

OBJECTIVES: To describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms. METHODS: This was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks. RESULTS: Data were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms. CONCLUSIONS: When used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

An Evaluation of By My Side: Peer Support in Written Form is Acceptable and Useful for Parents Bereaved by Childhood Cancer.

CONTEXT: Cancer is the leading cause of nonaccidental death in childhood, with the death of a child representing a devastating loss for families. Peer support offers a valuable way to support parents' adjustment in bereavement. The By My Side book provides written peer support by sharing bereaved parents' stories to normalize grief experiences and reduce parents' isolation. It is available free of charge. OBJECTIVES: This project evaluated the acceptability, relevance, emotional impact, and usefulness of By My Side. DESIGN: Bereaved parents and health care professionals (HCPs) provided feedback via a questionnaire. We used descriptive statistics and qualitative analysis of open-ended responses to analyze the data. SETTING/PARTICIPANTS: We mailed a study invitation and evaluation questionnaire to parents and HCPs who ordered a copy of By My Side. RESULTS: About 24 bereaved parents and seven HCPs provided feedback. Parents thought the book's length (91.7%) and amount of information (83.3%) was just right. About 75% of parents reported that the book made them feel that their reactions to their child's death were normal and/or appropriate. Parents reported positive and negative emotional reactions to the book (e.g., 87.5% felt comforted, 87.5% felt sadness). All parents and HCPs reported that the book provided useful information about grief. About 83.4% of parents and 85.7% of HCPs would recommend it to others. CONCLUSION: By My Side was acceptable and useful to bereaved parents and HCPs. Results suggest that peer support in written form may help normalize aspects of grief and comfort parents bereaved by childhood cancer.

Loss of Function in Escherichia coli Exposed to Environmentally Relevant Concentrations of Benzalkonium Chloride.

Assessing the risk of resistance associated with biocide exposure commonly involves exposing microorganisms to biocides at concentrations close to the MIC. With the aim of representing exposure to environmental biocide residues, Escherichia coli MG1655 was grown for 20 passages in the presence or absence of benzalkonium chloride (BAC) at 100 ng/liter and 1,000 ng/liter (0.0002% and 0.002% of the MIC, respectively). BAC susceptibility, planktonic growth rates, motility, and biofilm formation were assessed, and differentially expressed genes were determined via transcriptome sequencing. Planktonic growth rate and biofilm formation were significantly reduced (P < 0.001) following BAC adaptation, while BAC minimum bactericidal concentration increased 2-fold. Transcriptomic analysis identified 289 upregulated and 391 downregulated genes after long-term BAC adaptation compared with the respective control organism passaged in BAC-free medium. When the BAC-adapted bacterium was grown in BAC-free medium, 1,052 genes were upregulated and 753 were downregulated. Repeated passage solely in biocide-free medium resulted in 460 upregulated and 476 downregulated genes compared with unexposed bacteria. Long-term exposure to environmentally relevant BAC concentrations increased the expression of genes associated with efflux and reduced the expression of genes associated with outer-membrane porins, motility, and chemotaxis. This was manifested phenotypically through the loss of function (motility). Repeated passage in a BAC-free environment resulted in the upregulation of multiple respiration-associated genes, which was reflected by increased growth rate. In summary, repeated exposure of E. coli to BAC residues resulted in significant alterations in global gene expression that were associated with minor decreases in biocide susceptibility, reductions in growth rate and biofilm formation, and loss of motility.IMPORTANCE Exposure to very low concentrations of biocides in the environment is a poorly understood risk factor for antimicrobial resistance. Repeated exposure to trace levels of the biocide benzalkonium chloride (BAC) resulted in loss of function (motility) and a general reduction in bacterial fitness but relatively minor decreases in susceptibility. These changes were accompanied by widespread changes in the Escherichia coli transcriptome. These results demonstrate the importance of including phenotypic characterization in studies designed to assess the risks of biocide exposure.

A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat.

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model's features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles.

Does interprofessional simulation increase self-efficacy: a comparative study.

OBJECTIVES: In this work, we have compared uniprofessional and interprofessional versions of a simulation education intervention, in an attempt to understand more about whether it improves trainees' self-efficacy. BACKGROUND: Interprofessionalism has been climbing the healthcare agenda for over 50 years. Simulation education attempts to create an environment for healthcare professionals to learn, without potential safety risks for patients. Integrating simulation and interprofessional education can provide benefits to individual learners. SETTING: The intervention took place in a high-fidelity simulation facility located on the campus of a large urban hospital. The centre provides educational activities for an Academic Health Sciences Centre. Approximately 2500 staff are trained at the centre each year. PARTICIPANTS: One hundred and fifteen nurses and midwives along with 156 doctors, all within the early years of their postgraduate experience participated. All were included on the basis of their ongoing postgraduate education. METHODS: Each course was a one-day simulation course incorporating five clinical and one communication scenarios. After each a facilitated debriefing took place. A mixed methods approach utilised precourse and postcourse questionnaires measuring self-efficacy in managing emergency situations, communication, teamwork and leadership. RESULTS: Thematic analysis of qualitative data showed improvements in communication/teamwork and leadership, for doctors and nurses undergoing simulation training. These findings were confirmed by statistical analysis showing that confidence ratings improved in nurses and doctors overall (p<0.001). Improved outcomes from baseline were observed for interprofessional versus uniprofessional trained nurses (n=115; p<0.001). Postcourse ratings for doctors showed that interprofessional training was significantly associated with better final outcomes for a communication/teamwork dimension (n=156; p<0.05). CONCLUSIONS: This study provides evidence that simulation training enhances participants' self-efficacy in clinical situations. It also leads to increases in their perceived abilities relating to communication/teamwork and leadership/management of clinical scenarios. Interprofessional training showed increased positive effects on self-efficacy for nurses and doctors.

Method-specific serum cortisol responses to the adrenocorticotrophin test: comparison of gas chromatography-mass spectrometry and five automated immunoassays.

OBJECTIVE: The serum cortisol response to the adrenocorticotrophin (ACTH) test is known to vary significantly by assay, but lower reference limits (LRL) for this response have not been established by the reference gas chromatography-mass spectrometry (GC-MS) method or modern immunoassays. We aimed to compare the normal cortisol response to ACTH stimulation using GC-MS with five widely used immunoassays. DESIGN, PATIENTS AND MEASUREMENTS: An ACTH test (250 µg iv ACTH1-24 ) was undertaken in 165 healthy volunteers (age, 20-66 years; 105 women, 24 of whom were taking an oestrogen-containing oral contraceptive pill [OCP]). Serum cortisol was measured using GC-MS, Advia Centaur (Siemens), Architect (Abbott), Modular Analytics E170 (Roche), Immulite 2000 (Siemens) and Access (Beckman) automated immunoassays. The estimated LRL for the 30 min cortisol response to ACTH was derived from the 2·5th percentile of log-transformed concentrations. RESULTS: The GC-MS-measured cortisol response was normally distributed in males but not females, with no significant gender difference in baseline or post-ACTH cortisol concentration. Immunoassays were positively biased relative to GC-MS, except in samples from women on the OCP, who showed a consistent negative bias. The LRL for cortisol was method-specific [GC-MS: 420 nm; Architect: 430 nm; Centaur: 446 nm; Access 459 nm; Immulite (2000) 474 nm] and, for the E170, also gender-specific (female: 524 nm; male 574 nm). A separate LRL is necessary for women on the OCP. CONCLUSIONS: Normal cortisol responses to the ACTH test are influenced significantly by assay and oestrogen treatment. We recommend the use of separate reference limits in premenopausal women on the OCP and warn users that cortisol measurements in this subgroup are subject to assay interference.

Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release.

Ethosuximide is the drug of choice for treating generalized absence seizures, but its mechanism of action is still a matter of debate. It has long been thought to act by disrupting a thalamic focus via blockade of T-type channels and, thus, generation of spike-wave activity in thalamocortical pathways. However, there is now good evidence that generalized absence seizures may be initiated at a cortical focus and that ethosuximide may target this focus. In the present study we have looked at the effect ethosuximide on glutamate and GABA release at synapses in the rat entorhinal cortex in vitro, using two experimental approaches. Whole-cell patch-clamp studies revealed an increase in spontaneous GABA release by ethosuximide concurrent with no change in glutamate release. This was reflected in studies that estimated global background inhibition and excitation from intracellularly recorded membrane potential fluctuations, where there was a substantial rise in the ratio of network inhibition to excitation, and a concurrent decrease in excitability of neurones embedded in this network. These studies suggest that, in addition to well-characterised effects on ion channels, ethosuximide may directly elevate synaptic inhibition in the cortex and that this could contribute to its anti-absence effects. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Functional CB2 type cannabinoid receptors at CNS synapses.

To date, it has been thought that cannabinoid receptors in CNS are primarily of the CB1R subtype, with CB2R expressed only in glia and peripheral tissues. However, evidence for the expression of CB2 type cannabinoid receptors at neuronal sites in the CNS is building through anatomical localization of receptors and mRNA in neurons and behavioural studies of central effects of CB2R agonists. In the medial entorhinal area of the rat, we found that blockade of CB1R did not occlude suppression of GABAergic inhibition by the non-specific endogenous cannabinoid 2-AG, suggesting that CB1R could not account fully for the effects of 2-AG. Suppression could be mimicked using the CB2R agonist JWH-133 and reversed by the CB2R inverse agonist AM-630, indicating the presence of functional CB2R. When we reversed the order of drug application AM-630 blocked the effects of the CB2R agonist JWH-133, but not the CB1R inverse agonist LY320135. JTE-907, a CB2R inverse agonist structurally unrelated to AM-630 elicited increased GABAergic neurotransmission at picomolar concentrations. Analysis of mIPSCs revealed that CB2R effects were restricted to action potential dependent, but not action potential independent GABA release. These data provide pharmacological evidence for functional CB2R at CNS synapses.

Modulation of network oscillatory activity and GABAergic synaptic transmission by CB1 cannabinoid receptors in the rat medial entorhinal cortex.

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 microM), an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.