Subcutaneous tranexamic acid for bleeding associated with a mycotic aortic aneurysm.

We describe the case of a 64-year-old woman with haemoptysis due to a mycotic thoracic aneurysm, with probable fistulation into the lung and oesophagus. Continuous subcutaneous tranexamic acid was used at the end of life to minimise bleeding associated with this, once the oral route was lost. A 1.5 g of tranexamic acid was administered, diluted with 23 mL water for injection in a 30 mL syringe, as a continuous subcutaneous infusion over 24 hours. Bleeding ceased rapidly following administration. There was no further bleeding in the last days before death and no site reaction noted. This case report adds to the growing evidence base for the use of subcutaneous tranexamic acid in a palliative care setting. However, further research is needed to support this practice both in terms of efficacy and safety, but also terms of compatibility and stability when administered by continuous subcutaneous infusion.

UK Palliative trainees Research Collaborative (UK-PRC): the first 5 years - 0-100 study sites.

OBJECTIVES: Palliative care research suffers from underfunding and a workforce spread across multiple settings leading to a lack of large-scale studies. To facilitate multisite research and audit we set up the UK Palliative trainees Research Collaborative (UKPRC), the first national trainee-led audit and research collaborative in palliative care. Here, we critically review the progress and potential of the UKPRC since its inception in 2016, identifying key challenges and facilitators. Members of the UKPRC steering committee collaborated to write this reflection, reviewing existing evidence regarding trainee-led research collaboratives. FINDINGS: The UKPRC has representation from 16/19 UK training regions. Projects are run by a core team; local collaborators collect data at each site. The collaborative is supported by academic leads and newly qualified consultants to develop a culture of continuous improvement in practice. We have conducted four national projects to date, including an audit covering 119 sites. Facilitators for our work include a focus on inclusivity and national representation; support from recently qualified consultants to ensure continuity; and taking a pragmatic approach, focusing initially on straightforward projects to build momentum. Challenges include the step from national audit to multisite, patient-facing research and maintaining continuity in a membership with high turnover. CONCLUSIONS: There is potential to change practice through large scale data collection via the trainee-led collaborative model. Collaboration is especially important in a small specialty with limited resources. The UKPRC has demonstrated 'proof of concept' and has the potential to support and sustain a culture where research can flourish within palliative care.

Orodispersible and transmucosal alternative medications for symptom control in adults.

BACKGROUND: Paediatric palliative care makes frequent use of orodispersible and transmucosal drug delivery routes. The limited published experience of this practice suggests that it enables the delivery of needle-free symptom relief, with the potential to train family carers to administer anticipatory medications without reliance on trained health professionals. AIMS: To identify orodispersible and potential transmucosal alternatives that may be used in adults in the event of a patient having no oral or intravenous route and no access to subcutaneous injections. METHODS: The author panel identified medications through review of multiple drug formularies, review of the published evidence and their experience. Where possible, licensed alternatives were identified and any 'off label' or unlicensed medications clearly highlighted. RESULTS: A list of 27 medications is provided, which could be used either via the orodispersible or transmucosal alternative route for healthcare professionals delivering end of life care to consider when the licensed alternative routes are unavailable. All users of this guide are encouraged to use their professional judgement whenever selecting a medication for a patient, recognising that this review is neither a guideline nor a systematic review, and taking account of licensing considerations, adverse effects, potential unpredictability of time to effect and contraindications. CONCLUSION: Should it be necessary to use these orodispersible or transmucosal alternatives then any experience gained should be reported in the literature. Combined with further research, this experience offers the possibility of reducing injection frequency and inherent delays in medication administration, particularly in the community setting during the COVID-19 pandemic.

Fan therapy for cough: case report and literature review.

This case report describes the care of a 59-year-old woman with metastatic small cell lung cancer and chronic obstructive pulmonary disease who was highly symptomatic with an intractable cough. The patient reported a subjective benefit from a table fan. The authors observed an objective improvement with a marked reduction in cough frequency when the fan was in use. A literature review was undertaken and identified one randomised controlled trial assessing the use of fan for cough. The proposed underlying mechanism of cough relief is stimulation of the trigeminal nerve, possibly by cooling. This mechanism is well described in breathlessness. It presents the possibility of a novel therapeutic approach to managing cough. Further studies of both the role of nasal receptors in cough pathophysiology and the role of fan therapy in cough, where there is no concern of an airborne infectious pathogen such as COVID-19, are warranted.

Subcutaneous Levetiracetam for the Management of Seizures at the End of Life: An Audit and Updated Literature Review.

Objectives: The aim of this study is to report the results of a second cycle audit of the use of subcutaneous levetiracetam (Keppra®) and an updated literature review of management of seizures in palliative care patients. Methods: A comprehensive literature review on the use of subcutaneous levetiracetam performed in 2016 was updated. A retrospective audit of the use of subcutaneous levetiracetam for inpatients at Sir Michael Sobell House Hospice during the period of 2019-2020 was performed. Ethical approval was not required and was therefore not sought. Results: We report an additional 66 cases identified through an updated literature review and our audit. Fourteen articles were identified from the literature review, reporting a total of 120 cases where subcutaneous levetiracetam was administered. We report 19 further cases of subcutaneous levetiracetam administration between April 2019 and April 2020. Doses ranged from 500 mg to 4000 mg daily. Doses above 2000 mg were administered using a T60 syringe driver. The oral-to-subcutaneous conversion ratio was 1:1 in all but one case where the dose had to be reduced to fit a T34 syringe driver, after which the T60s were purchased. Levetiracetam was not mixed with other medications, but administered alone using water as the diluent for injection. Where necessary, the dose was appropriately adjusted for renal function. No site reactions were reported. Conclusions: Combined analysis of the 139 cases of subcutaneous levetiracetam administration suggests that this treatment continues to have a role in management of seizures at the end of life. Clinical outcomes suggest that therapeutic levels may be achieved, although there are only very limited data available with a few cases worldwide to support this. Randomized controlled trials are urgently needed to establish the efficacy and tolerability of subcutaneous levetiracetam administration.

Can video consultations replace face-to-face interviews? Palliative medicine and the Covid-19 pandemic: rapid review.

During the Covid-19 pandemic, a strategy to minimise face-to-face (FtF) visits and limit viral spread is essential. Video consultations offer clinical assessment despite restricted movement of people.We undertook a rapid literature review to identify the highest currently available level of evidence to inform this major change in clinical practice. We present a narrative synthesis of the one international and one national guideline and two systematic reviews-all published within the last 18 months.The global evidence appears to support video consultations as an effective, accessible, acceptable and cost-effective method of service delivery. Organisations must ensure software is simple, effective, reliable and safe, with the highest level of security for confidentiality.Although video consultations cannot fully replace FtF, they can radically reduce the need for FtF and the risk of Covid-19 spread in our communities while maintaining high standards of care. For patient safety, it will be critical to follow the WHO guidance regarding: a standard operating procedure; clinical protocols for when video consultations can (and cannot) be used; policies to ensure equity of access in disadvantaged populations; adequate staff training; and administrative support to coordinate appointments.

Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults.

BACKGROUND: Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness. OBJECTIVES: To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points. MAIN RESULTS: We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations.Olanzapine versus placebo/no treatmentPrimary outcomesOlanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomesFour studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis.Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy.We are uncertain if olanzapine reduces breakthrough nausea and vomiting (RR 0.38, 95% CI 0.10 to 1.47; 501 participants; 2 studies; I² = 54%) compared to placebo or no treatment. No studies reported 50% reduction in severity of nausea or vomiting, use of rescue antiemetics, or attrition.We are uncertain of olanzapine's efficacy in reducing acute nausea or vomiting. Olanzapine probably reduces delayed nausea (RR 1.71, 95% CI 1.40 to 2.09; 585 participants; 3 studies) and vomiting (RR 1.28, 95% CI 1.14 to 1.42; 702 participants; 5 studies).Subgroup analysis: 5 mg versus 10 mgPlanned subgroup analyses found that it is unclear if 5 mg is as effective an antiemetic as 10 mg. There is insufficient evidence to exclude the possibility that 5 mg may confer a lower risk of somnolence and fatigue than 10 mg.Other comparisonsOne study (20 participants) compared olanzapine versus NK1 antagonists. We observed no difference in any reported outcomes.One study (112 participants) compared olanzapine versus a prokinetic (metoclopramide), reporting that olanzapine may increase freedom from overall nausea (RR 2.95, 95% CI 1.73 to 5.02) and overall vomiting (RR 3.03, 95% CI 1.78 to 5.14).One study (62 participants) examined olanzapine versus 5-HT3 antagonists, reporting olanzapine may increase the likelihood of 50% or greater reduction in nausea or vomiting at 48 hours (RR 1.82, 95% CI 1.11 to 2.97) and 24 hours (RR 1.36, 95% CI 0.80 to 2.34).One study (229 participants) compared olanzapine versus dexamethasone, reporting that olanzapine may reduce overall nausea (RR 1.73, 95% CI 1.37 to 2.18), overall vomiting (RR 1.27, 95% CI 1.10 to 1.48), delayed nausea (RR 1.66, 95% CI 1.33 to 2.08) and delayed vomiting (RR 1.25, 95% CI 1.07 to 1.45). AUTHORS' CONCLUSIONS: There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg.We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.

Subcutaneous levetiracetam for the management of seizures at the end of life.

OBJECTIVES: To report the results of a combined case series analysis of subcutaneous levetiracetam (Keppra) for the management of seizures in palliative care patients. METHODS: A comprehensive literature review on the use of subcutaneous levetiracetam was performed, and these data were combined with a prospective observational audit of its use in terminal care undertaken in a regional palliative care network. RESULTS: 7 papers were identified from the literature review-four case reports and three observational case series-reporting on a total of 53 cases where subcutaneous levetiracetam was administered.We report 20 further cases of subcutaneous levetiracetam administration from a prospective observational audit. Doses ranged from 250mg to 4000 mg daily. Oral to subcutaneous conversion ratios where stated were 1:1. Levetiracetam was reported as the sole administered antiepileptic drug (AED) in eight cases, and no seizures were reported until death in five cases. Five were switched back to enteral levetiracetam. In seven cases, levetiracetam was combined with AEDs to provide seizure control at the end of life. There was one report of a sterile abscess after 25 days of continuous subcutaneous administration. CONCLUSIONS: Combined analysis of 73 reported cases of subcutaneous levetiracetam suggests this treatment may have a role in the management of seizures at the end of life. However, randomised controlled trials are urgently needed to establish the efficacy and tolerability of subcutaneous levetiracetam administration. If proven to be safe and effective, subcutaneous levetiracetam offers the potential to prevent and treat seizures without causing unnecessary sedation at the end of life.

Use of flax oil to influence honey bee nestmate recognition.

Fatty acids, normally found in comb wax, have a strong influence on nestmate recognition in honey bees, Apis mellifera L. Previous work has shown that bees from different colonies, when treated with 16- or 18-carbon fatty acids, such as oleic, linoleic, or linolenic acids, are much less likely to fight than bees from two colonies when only one of the two is treated. Previous work also shows that the influence of comb wax on recognition has practical applications; transfer of empty comb between colonies, before merger of those colonies, reduces fighting among workers within the merged colony. Flax oil contains many of the same fatty acids as beeswax. Here, we tested the hypothesis that treatment of individual bees with flax oil affects nestmate recognition; the results proved to be consistent with this hypothesis and showed that treated bees from different colonies were less likely to fight than untreated bees. These results suggest that flax oil may be useful in facilitating colony mergers.